Peptide Neuropeptides Research

Physiological Appetite Regulation and Bariatric Surgery.

Ramasamy, Indra · 2024

Appetite is regulated by two sets of neurons in the hypothalamus.

The Foundational Science of Endogenous Opioids and Their Receptors.

Tache, Simona · 2024

Four endogenous opioid peptide families (beta-endorphin, enkephalin, dynorphin, endomorphin) act through multiple receptor types (mu, delta, kappa, ORL1).

The subcommissural organ regulates brain development via secreted peptides.

Zhang, Tingting · 2024

SCO ablation caused severe hydrocephalus and neuronal developmental defects.

The life and times of endogenous opioid peptides: Updated understanding of synthesis, spatiotemporal dynamics, and the clinical impact in alcohol use disorder.

Margolis, Elyssa B · 2023

This comprehensive review maps the current understanding of over two dozen endogenous opioid peptides — the body's natural painkillers and reward signals.

Agrp-negative arcuate NPY neurons drive feeding under positive energy balance via altering leptin responsiveness in POMC neurons.

Qi, Yue · 2023

The researchers identified a previously unknown population of AgRP-negative NPY neurons in the arcuate nucleus of the hypothalamus.

Immunogenicity of biologic therapies for migraine: a review of current evidence.

Cohen, Joshua M · 2021

ADA prevalence ranged from <1% to ~18% and neutralizing ADA from 0-12% across CGRP mAbs, with adverse events related to ADA formation rare across all four approved migraine antibodies..

Efficacy of calcitonin gene-related peptide (CGRP) receptor blockers in reducing the number of monthly migraine headache days (MHDs): A network meta-analysis of randomized controlled trials.

Masoud, Ahmed Taher · 2021

At 6 weeks: fremanezumab 900mg most effective (SMD=-0.55).

Monoclonal Antibodies Targeting CGRP: From Clinical Studies to Real-World Evidence-What Do We Know So Far?

Mavridis, Theodoros · 2021

Real-world evidence for anti-CGRP monoclonal antibodies shows efficacy consistent with or exceeding clinical trial results, with maintained favorable safety profiles in routine clinical practice..

Rimegepant: acute treatment for migraine headaches.

Peters, Golden L · 2021

Rimegepant is a small molecule that blocks the CGRP receptor.

Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder.

Sikich, Linmarie · 2021

Intranasal oxytocin (48 IU daily for 24 weeks) showed no significant improvement in social withdrawal (ABC-mSW: -3.7 vs -3.5 placebo, p=0.61) or secondary outcomes in 290 children with autism..

The locus of Action of CGRPergic Monoclonal Antibodies Against Migraine: Peripheral Over Central Mechanisms.

González-Hernández, Abimael · 2020

The review analyzes evidence on four FDA-approved anti-CGRP monoclonal antibodies: erenumab, fremanezumab, galcanezumab, and eptinezumab.

Calcitonin Gene-Related Peptide (CGRP) Antagonists and Their Use in Migraines.

Henson, Brianna · 2020

Three FDA-approved CGRP antagonists and four more in clinical development demonstrate consistent efficacy in reducing migraine attacks with favorable safety profiles..

Calcitonin Gene-Related Peptide Antagonists as a Savior in Episodic and Chronic Migraine: A Review.

Pervez, Hira · 2020

All four anti-CGRP monoclonal antibodies demonstrated significant reductions in monthly migraine days across multiple Phase 2-3 clinical trials, with favorable safety profiles compared to existing preventive treatments..

Monoclonal antibodies blocking CGRP transmission: An update on their added value in migraine prevention.

Schoenen, J · 2020

CGRP/receptor-targeting monoclonal antibodies represent a paradigm shift from repurposed treatments to migraine-specific prevention, with strong clinical trial evidence supporting their efficacy and favorable safety profiles..

Medications Approved for Preventing Migraine Headaches.

Spindler, Brittany L · 2020

Three CGRP-targeting monoclonal antibodies are FDA-approved for migraine prevention, reducing attack frequency through a targeted mechanism not available with older drugs..

Orlistat inhibition of intestinal lipase acutely increases appetite and attenuates postprandial glucagon-like peptide-1-(7-36)-amide-1, cholecystokinin, and peptide YY concentrations.

Ellrichmann, Mark · 2008

Orlistat inhibition of intestinal lipase acutely increased appetite and attenuated GLP-1/PYY satiety responses, proving that fat absorption (not just fat presence) is required for satiety hormone release — the gut must PROCESS fat to signal fullness..

Cholecystokinin.

Chandra, Rashmi · 2007

CCK operates as both the primary gut satiety signal (reducing meal size through vagal afferent and brain CCK-A receptors) and a digestive coordinator (gallbladder contraction, pancreatic secretion) — the most comprehensively characterized gut hormone..

Gastrointestinal hormones regulating appetite.

Chaudhri, Owais · 2006

Comprehensive mapping of GI appetite hormones: ghrelin as the sole orexigenic signal; GLP-1, PYY3-36, oxyntomodulin, CCK, amylin, PP, and bombesin/GRP as anorexigenic signals — each acting through distinct receptors and pathways for integrated satiety control..

Attenuated peptide YY release in obese subjects is associated with reduced satiety.

le Roux, C W · 2006

Obese subjects demonstrated attenuated postprandial PYY3-36 release compared to lean controls, with reduced PYY correlating with diminished subjective satiety — PYY deficiency contributes to impaired meal-related fullness signaling in obesity..

Gut peptides in the regulation of food intake and energy homeostasis.

Murphy, Kevin G · 2006

Complete 2006 mapping of gut peptide appetite regulation: GLP-1 and PYY3-36 as top obesity targets, with CCK, oxyntomodulin, amylin, and PP providing complementary satiety signals — ghrelin as the sole orexigenic gut peptide..

Gastric sensorimotor functions and hormone profile in normal weight, overweight, and obese people.

Vazquez Roque, Maria I · 2006

Gastric accommodation, sensitivity, emptying, and gut hormones (ghrelin, CCK, PYY) showed progressive changes from normal through overweight to obese, with disrupted fasting/postprandial hormone profiles providing the hormonal basis for weight-dependent appetite dysfunction..

Fat in the intestine as a regulator of appetite--role of CCK.

Beglinger, Christoph · 2004

Intestinal fat is the most potent CCK-releasing macronutrient, with CCK mediating fat-induced satiety through vagal afferent and brain pathways — the primary mechanism for the high satiating power of dietary fat..

The clinical relevance of adrenomedullin: a promising profile?

Bunton, David C · 2004

Adrenomedullin has clinical relevance as both a biomarker (predicting outcomes in sepsis, HF, ACS) and a potential therapeutic (improving hemodynamics, protecting kidneys, reducing inflammation) — a dual biomarker-therapy peptide..

Biomarkers of satiation and satiety.

de Graaf, Cees · 2004

CCK and GLP-1 are the most validated satiety biomarkers correlating with both subjective appetite ratings and actual food intake, with PYY, ghrelin, insulin, and glucose providing complementary information in multi-marker panels..

Peripheral signals in the control of satiety and hunger.

Drazen, Deborah L · 2003

Satiety is controlled by a two-tier peripheral signaling system: short-term gut peptides (CCK, GLP-1, PYY, ghrelin, oxyntomodulin) for meal control and long-term adiposity signals (leptin, insulin) for body weight regulation, integrated by brainstem and hypothalamic circuits..

Neuropeptide systems as novel therapeutic targets for depression and anxiety disorders.

Holmes, Andrew · 2003

Multiple neuropeptide systems (CRF, NPY, substance P/NK1, galanin, vasopressin, nociceptin) offer novel antidepressant and anxiolytic targets with mechanisms fundamentally different from monoamine-based drugs..

The pharmacology of CP-154,526, a non-peptide antagonist of the CRH1 receptor: a review.

Seymour, Patricia A · 2003

CP-154,526 showed anxiolytic effects across multiple animal models, antidepressant activity, and HPA axis modulation without sedation, providing the most comprehensive validation of CRF1 antagonism as a psychiatric drug mechanism..

Cloning and functional expression of a human Y4 subtype receptor for pancreatic polypeptide, neuropeptide Y, and peptide YY.

Bard, J A · 1995

The human Y4 receptor was cloned and shown to bind pancreatic polypeptide, NPY, and PYY, expanding the known receptor family for these appetite-regulating peptides..

Expression cloning and pharmacological characterization of a human hippocampal neuropeptide Y/peptide YY Y2 receptor subtype.

Gerald, C · 1995

The human Y2 receptor was cloned from hippocampus and shown to selectively bind NPY and PYY but not pancreatic polypeptide..

Treatment of growth hormone-deficient adults with recombinant human growth hormone increases the concentration of growth hormone in the cerebrospinal fluid and affects neurotransmitters.

Johansson, J O · 1995

One month of GH replacement increased CSF GH and IGF-1 while altering monoamine metabolites, neuropeptides, and opioid peptide concentrations..

Identification of dynorphins as endogenous ligands for an opioid receptor-like orphan receptor.

Zhang, S · 1995

Dynorphin peptides activate a cloned orphan receptor with high sequence homology to opioid receptors, functioning as its endogenous ligands via G protein-coupled potassium channel activation..

Substance P and the trigeminovascular system: From preclinical mechanisms to human headache induction.

Alpay, Berkay · 2025

Comprehensive review of substance P role in the trigeminovascular system covers preclinical mechanisms and clinical translation for migraine pathophysiology and treatment..

Thermal challenge and food intake: Mutual regulatory mechanisms.

Alpár, Alán · 2025

Review of how thermal challenge and food intake are mutually regulated through NPY and melanocortin neuropeptide pathways, revealing brain energy homeostasis mechanisms..

Psychological and behavioral effects of GLP-1 and GIP agonists in weight loss: a comprehensive review.

Ameer, Fatima · 2025

Review of psychological and behavioral effects of GLP-1/GIP agonists covers mood, food reward, addiction, cognition, and mental health implications of these metabolic drugs..

The dual role of ACE2 in viral infections and neurodegeneration: mechanisms and therapeutic opportunities.

Amelimojarad, Melika · 2025

Review of ACE2's dual role as both SARS-CoV-2 entry receptor and neuroprotective enzyme explores how viral infections and neurodegeneration intersect through this peptide-processing enzyme..

Mechanisms of GLP-1 in Modulating Craving and Addiction: Neurobiological and Translational Insights.

Amorim Moreira Alves, Gabriel · 2025

Review of GLP-1 drug mechanisms in craving and addiction covers neurobiological pathways through which these peptides modulate reward circuits, substance use, and addictive behavior..

Neuroendocrine Regulation and Neural Circuitry of Parenthood: Integrating Neuropeptides, Brain Receptors, and Maternal Behavior.

Leff-Gelman, Philippe · 2025

Maternal behavior is orchestrated by a network of neuropeptides — primarily oxytocin, prolactin, and placental lactogens — that physically reshape the mother's brain during pregnancy and the postpartum period.

Chronic Tendinopathy Driven by Neoinnervation: The Role of the Paratenon, Upregulated Neural Biomarkers, and Evolving Evidence - A Scoping Review.

Palee, Suwannika · 2025

Neuropeptides including substance P and CGRP are consistently upregulated in chronic tendinopathy, with the paratenon serving as a key source of neoinnervation that drives ongoing pain signaling..

Anti‑CGRP monoclonal antibodies in resistant migraine: preliminary real-world effectiveness and clinical predictors of response at two years.

Pons-Fuster, E · 2024

Anti-CGRP monoclonal antibodies reduced monthly migraine days, disability scores (MIDAS and HIT-6), and acute medication intake over a 24-month period in 120 resistant migraine patients.

Evaluation of outcomes of calcitonin gene-related peptide (CGRP)-targeting therapies for acute and preventive migraine treatment based on patient sex.

Porreca, Frank · 2024

For acute migraine treatment, the three approved gepant drugs produced strong, statistically significant effects in women.

Real-world experience of galcanezumab in the prevention of migraine in Spain: a systematic literature review.

Pozo-Rosich, Patricia · 2024

Across 29 real-world Spanish studies, galcanezumab showed consistent reductions in monthly migraine days and monthly headache days.

Somatostatin peptides prevent increased human colonic epithelial permeability induced by hypoxia.

Rajput, Ibrahim · 2024

Chemical hypoxia (using DNP) increased paracellular permeability in human colon by 52% (p = 0.003).

Medication "underuse" headache.

Rattanawong, Wanakorn · 2024

The review identifies four forms of medication underuse in migraine: 1.

Evolution of neuropeptide Y/RFamide-like receptors in nematodes.

Reinhardt, Franziska · 2024

Using an automated computational pipeline based on ExonMatchSolver, researchers identified 1,557 NPY/RFamide-like receptors across 159 nematode genomes: 1,100 NPR-type, 375 FRPR-type, and 82 C09F12.3-type receptors. The receptor family is generally well-conserved across the nematode phylum, suggesting these receptors play essential roles.

Neuropeptide Y in first-episode schizophrenia: is there any sex differences in the pathogeneses of schizophrenia?

Song, Jia-Qi · 2024

Serum NPY levels were significantly higher in first-episode schizophrenia patients than controls (p<0.001).

The influence of neuropeptide Y (NPY) on the relationship between emotion regulation and mood-related pathology in survivors of childhood interpersonal trauma.

Stevens, Sarah K · 2024

Difficulties in emotion regulation significantly predicted psychopathology (B=0.032, p<0.01).

TRESK channel activation ameliorates migraine-like pain via modulation of CGRP release from the trigeminovascular system and meningeal mast cells in experimental migraine models.

Torun, Ibrahim Ethem · 2024

TRESK activation by cloxyquin reduced CGRP release, allodynia, and mast cell degranulation in migraine models, with all effects specifically blocked by TRESK inhibitor A2764 and synergistic with sumatriptan ex vivo..

TRPV1-positive sensory nerves and neuropeptides are involved in epidermal barrier repair after tape stripping in mice.

Usui, Kenji · 2024

TRPV1-positive sensory nerves and neuropeptides (substance P and CGRP) are required for epidermal barrier repair after tape stripping, with involvement of filaggrin biosynthesis in the restoration process..

Beyond insulin: The Intriguing role of GLP-1 in Parkinson's disease.

Verma, Aanchal · 2024

GLP-1 receptor agonists show neuroprotective, anti-inflammatory, and neurotrophic properties in Parkinson's disease models, with the diabetes-PD link providing mechanistic rationale for therapeutic repurposing..

Exendin-4: A potential therapeutic strategy for Alzheimer's disease and Parkinson's disease.

Verma, Aanchal · 2024

Exendin-4 demonstrates neuroprotective effects against both Alzheimer's and Parkinson's disease in preclinical models, operating through anti-inflammatory, anti-oxidative, and neurotrophic mechanisms..

Understanding the Biological Relationship between Migraine and Depression.

Viudez-Martínez, Adrián · 2024

Multiple neuropeptide systems (CGRP, PACAP, substance P, neuropeptide Y, orexins) provide overlapping biological substrates for both migraine and depression, explaining their strong bidirectional clinical relationship..

Role of neuropeptides in orofacial pain: A literature review.

Wang, Jian · 2024

Neuropeptides in the trigeminal system play distinct roles: CGRP, substance P, NPY, NKA, HK-1, and VIP are pro-inflammatory and pro-nociceptive, while opioid peptides, galanin, oxytocin, and orexin-A are analgesic — identifying multiple therapeutic targets for orofacial pain..

Nociceptor mechanisms underlying pain and bone remodeling via orthodontic forces: toward no pain, big gain.

Wang, Sheng · 2024

TRPV1-expressing periodontal nociceptors release neuropeptides (CGRP, substance P) that mediate orthodontic pain and may also regulate alveolar bone remodeling during tooth movement, creating a dual neuroskeletal interaction..

Substance P regulates memory Th17 cell generation and maintenance in chronic dry eye disease.

Wang, Shudan · 2024

Substance P promotes memory Th17 cell generation and maintenance in chronic dry eye disease via NK1R, and in vivo NK1R antagonist treatment disrupts both memory Th17 formation and persistence..

Targeting IGF1/IGF1r signaling relieve pain and autophagic dysfunction in NTG-induced chronic migraine model of mice.

Wang, Tianxiao · 2024

IGF1r antagonist picropodophyllin alleviated chronic migraine-related pain behaviors and reduced CGRP and c-Fos expression in the trigeminal nucleus caudalis, identifying IGF1/IGF1r signaling as a contributor to chronic migraine..

Validity of Plasma Neuropeptide Y in Combination with Clinical Factors in Predicting Neuralgia Following Herpes Zoster.

Wu, Dan · 2024

Low plasma NPY levels independently predicted PHN development in 182 herpes zoster patients, and combining NPY with clinical factors (age, pain severity, rash area) improved predictive accuracy from AUC 0.804 to 0.873..

Substance P Promotes Leukocyte Infiltration in the Liver and Lungs of Mice with Sepsis: A Key Role for Adhesion Molecules on Vascular Endothelial Cells.

Zhu, Zhixing · 2024

Substance P promoted leukocyte infiltration into liver and lungs during acute pancreatitis in mice, revealing a neuropeptide-mediated mechanism for multi-organ damage..

Targeting NK-1R attenuates renal fibrosis via modulating inflammatory responses and cell fate in chronic kidney disease.

Zhu, Enyi · 2023

The neuropeptide substance P (SP) and its receptor NK-1R were found to be elevated in both patients with chronic kidney disease and in mice with induced kidney obstruction.

Anorectic and aversive effects of GLP-1 receptor agonism are mediated by brainstem cholecystokinin neurons, and modulated by GIP receptor activation.

Costa, Alessia · 2022

Using genetic tools to manipulate specific neuron populations in mice, researchers showed that CCK-expressing neurons in the caudal brainstem are required for the full appetite-suppressing and body weight-lowering effects of the GLP-1 receptor agonist exendin-4.

Real-World Evidence for Control of Chronic Migraine Patients Receiving CGRP Monoclonal Antibody Therapy Added to OnabotulinumtoxinA: A Retrospective Chart Review.

Blumenfeld, Andrew M · 2021

Combination of CGRP mAbs with onabotulinumtoxinA reduced monthly headache days by an additional 3.5-4.0 beyond Botox alone, with 45.1% achieving meaningful disability improvement..

Evaluation of the Safety of Calcitonin Gene-Related Peptide Antagonists for Migraine Treatment Among Adults With Raynaud Phenomenon.

Breen, Ilana D · 2021

5.3% of migraine patients with Raynaud phenomenon experienced microvascular complications from CGRP antagonists, including rare but serious events like gangrene requiring digit amputation..

Hunger and Satiety Peptides: Is There a Pattern to Classify Patients with Prader-Willi Syndrome?

Bueno, Marta · 2021

Cluster analysis separated PWS patients (23/27) into a distinct group with paradoxically elevated levels of both hunger (ghrelin) and satiety (leptin, PYY, GIP, GLP-1) hormones, suggesting hormonal dysfunction rather than simple imbalance..

Can a Higher Protein/Low Glycemic Index vs. a Conventional Diet Attenuate Changes in Appetite and Gut Hormones Following Weight Loss? A 3-Year PREVIEW Sub-study.

Buso, Marion E C · 2021

Higher-protein, low-GI diet for weight maintenance did not attenuate post-weight-loss changes in ghrelin or PYY compared to moderate-protein diet, and appetite hormone changes did not predict weight regain over 3 years..

cAMP signaling through protein kinase A and Epac2 induces substance P release in the rat spinal cord.

Chen, Wenling · 2021

cAMP drives substance P release through dual PKA and Epac2 pathways, but Epac2's contribution is selectively lost during latent pain sensitization, potentially reflecting chronic pain-related neural remodeling..

Inhibition of angiotensin converting enzyme induces mechanical allodynia through increasing substance P expression in mice.

Choi, Jae-Gyun · 2021

ACE inhibitors increase substance P levels in spinal cord and DRG, causing mechanical allodynia through NK-1R signaling.

Substance P Serves as a Balanced Agonist for MRGPRX2 and a Single Tyrosine Residue Is Required for β-Arrestin Recruitment and Receptor Internalization.

Chompunud Na Ayudhya, Chalatip · 2021

Substance P serves as a balanced agonist for MRGPRX2, activating both G-protein and β-arrestin pathways.

MRGPRX2 sensing of cationic compounds-A bridge between nociception and skin diseases?

Corbière, Auriane · 2021

MRGPRX2 acts as a broad sensor for cationic molecules, enabling mast cells to bridge nociception and skin inflammation, contributing to pruritus, pain, atopic dermatitis, and drug-induced reactions..

NK1 antagonists attenuate tau phosphorylation after blast and repeated concussive injury.

Corrigan, Frances · 2021

NK1 receptor antagonists attenuated tau hyperphosphorylation after blast and concussive TBI by modulating Akt, ERK1/2, and JNK kinases, with the mechanism initiated by TRPV1 mechanoreceptor-mediated substance P release..

Differences between adult and adolescent male mice in approach/avoidance and expression of hippocampal NPY in response to acute footshock.

Cortes, Mariana A · 2021

After footshock stress, adolescent mice showed elevated hippocampal NPY and no anxiety increase, while adult mice showed reduced hippocampal NPY and increased anxiety — opposite neuropeptide responses to the same stressor..

Appetite, the enteroendocrine system, gastrointestinal disease and obesity.

Crooks, Benjamin · 2021

Postprandial gut peptide hormones may not play a dominant role in normal appetite regulation in healthy individuals; their impact may be more significant in GI disease states where levels become supraphysiological..

CGRP Inhibitors and Oxidative Stress Biomarkers in Resistant Migraine: A Real-Life Study with Erenumab, Fremanezumab, and Galcanezumab.

De Luca, Ciro · 2021

CGRP inhibitors reduced AOPP (oxidative stress biomarker) over 6 months alongside 70% responder rates and significant improvements in disability, allodynia, fatigue, anxiety, and sleep quality in resistant migraineurs..

Involvement of substance P, osteopontin and satellite glial cells on photobiomodulation-induced antinociceptive effect in an experimental model of dentin hypersensitivity.

de Oliveira, Victhor Teixeira · 2021

PBM at 660nm and 808nm reversed dentin hypersensitivity by reducing substance P in the dentin-pulp complex and trigeminal ganglia, suppressing glial activation (GFAP), and increasing osteopontin expression for tissue repair..

Experimentally induced spine osteoarthritis in rats leads to neurogenic inflammation within neurosegmentally linked myotomes.

Duarte, Felipe C K · 2021

Spine facet osteoarthritis increased substance P, CGRP, PAR2, and CaMKII in neurosegmentally linked rectus femoris muscle but not in unlinked biceps brachii, with pain sensitization (allodynia, thermal hyperalgesia) at 7, 14, and 21 days post-surgery..

Neurokinins and their receptors in the rat trigeminal system: Differential localization and release with implications for migraine pain.

Edvinsson, Jacob Ca · 2021

Substance P release from stimulated dura mater, trigeminal ganglion neurons, and fibers was comparatively minor compared to CGRP release, explaining the clinical failure of NK1R antagonists for migraine while validating CGRP as the primary target..

Blocking NK1 receptors disrupts the sequential and temporal organization of chain grooming in rats.

Favila, Natalia · 2021

NK1 receptor antagonist L-733,060 made grooming chain transitions significantly more variable, simplified grooming bout structure, and increased transitions from active to inactive states — indicating substance P is critical for sequential action implementation..

CAPS2 Deficiency Impairs the Release of the Social Peptide Oxytocin, as Well as Oxytocin-Associated Social Behavior.

Fujima, Shuhei · 2021

CAPS2 knockout mice had reduced plasma but increased hypothalamic/pituitary oxytocin levels (release failure).

Oxytocin-induced increase in N,N-dimethylglycine and time course of changes in oxytocin efficacy for autism social core symptoms.

Kato, Yasuhiko · 2021

Oxytocin increased N,N-dimethylglycine (FDR p=0.043, d=0.74; N=83).

Evidence that increased cholecystokinin (CCK) in the periaqueductal gray (PAG) facilitates changes in Resident-Intruder social interactions triggered by peripheral nerve injury.

Keay, Kevin A · 2021

Chronic nerve injury increased CCK mRNA in ventrolateral PAG and dorsal raphe neurons and CCK-8 peptide in PAG terminal boutons.

The role of central corticotrophin-releasing factor receptor signalling in plasma glucose maintenance through ghrelin secretion in calorie-restricted mice.

Kimura, Risa · 2021

Central CRF-R signaling → sympathetic activation → ghrelin secretion → plasma glucose maintenance during 60% calorie restriction.

Intranasal oxytocin administration ameliorates social behavioral deficits in a POGZWT/Q1038R mouse model of autism spectrum disorder.

Kitagawa, Kohei · 2021

POGZWT/Q1038R mice showed social deficits and reduced OXTR expression.

A novel, injury-free rodent model of vulnerability for assessment of acute and preventive therapies reveals temporal contributions of CGRP-receptor activation in migraine-like pain.

Kopruszinski, Caroline M · 2021

Novel injury-free two-hit hyperalgesic priming model produced CGRP-dependent migraine-like pain in mice.

Corneal lymphangiogenesis in dry eye disease is regulated by substance P/neurokinin-1 receptor system through controlling expression of vascular endothelial growth factor receptor 3.

Lee, Seok Jae · 2021

SP/NK1R system promotes corneal lymphangiogenesis in DED by upregulating VEGFR3 expression on HDLECs.

Nociceptor neurons promote IgE class switch in B cells.

Mathur, Shreya · 2021

Nociceptor ablation/silencing substantially reduced allergic inflammation and IgE production in airway and skin models.

Randomized clinical trial shows no substantial modulation of empathy-related neural activation by intranasal oxytocin in autism.

Mayer, Annalina V · 2021

Randomized clinical trial showed no substantial modulation of empathy-related behavioral or neural responses by intranasal oxytocin administration compared to placebo..

Pituitary adenylate cyclase-activating polypeptide/vasoactive intestinal peptide (Part 2): biology and clinical importance in central nervous system and inflammatory disorders.

Moody, Terry W · 2021

PACAP plays an important role in the pathogenesis of headaches (particularly migraine), post-traumatic stress disorder, and drug/alcohol/smoking addiction.

Metaplastic contribution of neuropeptide Y receptors to spatial memory acquisition.

Méndez-Couz, Marta · 2021

Hippocampal Y2R blockade improved spatial memory, and learning dynamically changed Y2R/Y1R expression in hippocampus and prefrontal cortex..

A Review on the Role of Food-Derived Bioactive Molecules and the Microbiota-Gut-Brain Axis in Satiety Regulation.

Pizarroso, Nuria A · 2021

Three gut peptide hormones — CCK, GLP-1, and PYY — serve as the primary signaling molecules in the satiety system, released by enteroendocrine cells (EECs) in response to specific macronutrients detected through nutrient-sensing receptors.

The Multifaceted Mas-Related G Protein-Coupled Receptor Member X2 in Allergic Diseases and Beyond.

Quan, Paola Leonor · 2021

MRGPRX2 on mast cells recognizes an unusually diverse set of ligands: Natural ligands: host defense peptides, substance P, VIP, eosinophil granule proteins Drug ligands: compound 48/80, mastoparan (bee venom), quinolone antibiotics, neuromuscular blockers, morphine, vancomycin In host defense, the mouse homolog Mrgprb2 helps mast cells detect bacterial peptides and release antimicrobial peptides and immune mediators. In disease: - MRGPRX2 is linked to non-IgE drug hypersensitivity reactions (explaining why some people react to certain drugs without allergies) - Implicated in asthma, atopic dermatitis, contact dermatitis, and chronic spontaneous urticaria - May play a role in chronic inflammation through persistent mast cell activation - Also involved in tissue homeostasis and repair.

Membrane and nuclear initiated estrogenic regulation of homeostasis.

Stincic, Todd L · 2021

Estrogen coordinates kisspeptin, POMC, and AgRP neurons through dual membrane-initiated and nuclear signaling cascades, linking reproductive control with energy homeostasis in the hypothalamus..

Kisspeptin enhances brain responses to olfactory and visual cues of attraction in men.

Comninos, Alexander N · 2020

In 33 healthy men, kisspeptin enhanced limbic brain activity (amygdala, caudate, putamen, thalamus) to olfactory and visual attraction cues, enhanced penile tumescence, and increased attraction scores..

Substance P induces sympathetic immune response in the contralateral eye after the first eye cataract surgery in type 2 diabetic patients.

Gong, Xianhui · 2020

In diabetic patients, Substance P (SP) and MCP-1 levels both rose significantly in the contralateral (opposite) eye after the first cataract surgery, whether the second surgery was 1 day or 1 week later (P ≤ 0.040).

Targeting oxytocin receptor (Oxtr)-expressing neurons in the lateral septum to restore social novelty in autism spectrum disorder mouse models.

Horiai, Machi · 2020

Two different autism spectrum disorder (ASD) mouse models were used.

Substance P enhances the local activation of NK1R-expressing c-kit+ cardiac progenitor cells in right atrium of ischemia/reperfusion-injured heart.

Jeong, Yun-Mi · 2020

After ischemia/reperfusion injury in rats, Substance P (5 nmol/kg injection) had specific effects on the right atrium (RA): SP promoted expression of c-Kit, GATA4, Oct4, Nanog, and Sox2 only in the RA, not in other heart chambers.

Therapeutic hypothermia after cardiac arrest increases the plasma level of B-type natriuretic peptide.

Kashiwagi, Yusuke · 2020

Plasma BNP levels increased more than fivefold during therapeutic hypothermia (logarithmically from 1.98 to 2.63, P < 0.01).

Alcohol dependence potentiates substance P/neurokinin-1 receptor signaling in the rat central nucleus of amygdala.

Khom, S · 2020

In normal rats, substance P increased GABA release in the central amygdala, and blocking the NK-1 receptor decreased it.

The endomorphin-1/2 and dynorphin-B peptides display biased agonism at the mu opioid receptor.

LaVigne, Justin · 2020

Endomorphin-1 and endomorphin-2 showed a bias toward cAMP signaling at the mu opioid receptor (MOR), while dynorphin-B showed a bias toward G-protein (35S-GTPgammaS) signaling.

CCL17 in Inflammation and Pain.

Lee, Kevin M-C · 2020

A GM-CSF→CCL17 pathway in macrophages drives inflammatory pain through nerve growth factor, CGRP, and substance P signaling in non-bone-marrow-derived cells..

Resolvin D3 controls mouse and human TRPV1-positive neurons and preclinical progression of psoriasis.

Lee, Sang Hoon · 2020

Resolvin D3 reversed psoriasiform itch and prevented skin inflammation by inhibiting TRPV1 and reducing CGRP in sensory neurons, with confirmed activity in human DRG neurons..

Primary culture of the rat spinal dorsal horn: a tool to investigate the effects of inflammatory stimulation on the afferent somatosensory system.

Leisengang, Stephan · 2020

Short-term inflammation reduces neuronal substance P responsiveness while long-term low-dose inflammation enhances glutamate sensitivity, with microglia driving the inflammatory cascade..

Profiling of inflammatory mediators in the synovial fluid related to pain in knee osteoarthritis.

Li, Li · 2020

IL-1β, IL-6, and TNF-α in synovial fluid correlated with pain in early knee OA, but CGRP, substance P, neuropeptide Y, and matrix enzymes (MMP-3/13) did not correlate with pain scores..

Effects of inhalation of sevoflurane at different concentrations on TRPV1 in airways of rats at different developmental stages.

Liu, Dexing · 2020

Low-dose sevoflurane upregulated TRPV1 and airway neuropeptides (CGRP, SP, NKA, NKB) in developing rats but not in mature rats, with effects blocked by TRPV1 antagonist capsazepine..

Sensory neurons directly promote angiogenesis in response to inflammation via substance P signaling.

Liu, Lingjia · 2020

Sensory neurons from dry eye mice promoted vascular endothelial cell proliferation and tube formation via substance P signaling; blocking SP with spantide I prevented corneal neovascularization..

Lactobacillus plantarum PS128 Ameliorated Visceral Hypersensitivity in Rats Through the Gut-Brain Axis.

Liu, Yen-Wenn · 2020

PS128 reversed 5-HTP-induced visceral hypersensitivity and normalized substance P, CGRP, BDNF, and NGF distribution between dorsal root ganglia and spinal cord..

A Randomized Controlled Trial of Intranasal Neuropeptide Y in Patients With Major Depressive Disorder.

Mathé, Aleksander A · 2020

Single-dose intranasal NPY (6.8 mg) reduced MADRS by 10.3 points at 24h vs 5.6 for placebo (P=0.04, d=0.67) in MDD patients; effect not significant at 48h..

Sex Differences in the Neuropeptide Y System and Implications for Stress Related Disorders.

Nahvi, Roxanna J · 2020

Females have lower baseline NPY expression in multiple brain regions than males, with sex-dependent differences in NPY's anxiolytic and antidepressant effects and stress-responsive expression patterns..

Continuous infusion of substance P inhibits acute, but not subacute, inflammatory pain induced by complete Freund's adjuvant.

Nakamura, Yoki · 2020

Striatal substance P via NK1 receptors provides antinociception in acute (3-day) but not subacute (7-day) inflammatory pain, due to inflammation-induced NK1 receptor downregulation..

Continuous infusion of substance P into rat striatum relieves mechanical hypersensitivity caused by a partial sciatic nerve ligation via activation of striatal muscarinic receptors.

Nakamura, Yoki · 2020

Continuous striatal substance P infusion dose-dependently relieved neuropathic pain via NK1 receptors activating muscarinic cholinergic neurons — a novel brain-based analgesic pathway..

Tachykinin signaling in the control of puberty onset.

Navarro, Víctor M · 2020

Tachykinins (NKB, NKA, substance P) initiate puberty by stimulating kisspeptin neuron activation in the hypothalamus, with loss of tachykinin signaling causing delayed/absent puberty in humans and mice..

Amygdala, neuropeptides, and chronic pain-related affective behaviors.

Neugebauer, Volker · 2020

The amygdala contains a rich neuropeptide network where CGRP, CRF, oxytocin, vasopressin, opioids, neuropeptide S, and somatostatin interact to modulate pain processing and emotional-affective pain behaviors..

Dietary protein modulates digestive enzyme activities and gene expression in red tilapia juveniles.

Santos, W M · 2020

The 30% CP diet optimized growth, while 42% CP decreased ghrelin and insulin expression, increased CCK and peptide YY expression, and reduced growth performance compared to moderate protein levels..

Pancreatic Polypeptide but Not Other Members of the Neuropeptide Y Family Shows a Moderate Association With Perceived Anxiety in Obese Men.

Schaper, Selina Johanna · 2020

Pancreatic polypeptide (PP) plasma levels showed a moderate association with perceived anxiety specifically in obese men.

Physiological and Therapeutic Roles of Neuropeptide Y on Biological Functions.

Shende, Pravin · 2020

NPY acts through multiple receptor subtypes (Y1-Y5) to regulate appetite, cardiovascular tone, respiratory function, GI motility, and endocrine systems, with therapeutic implications for multiple disease areas..

Neuropeptide Y deficiency induces anxiety-like behaviours in zebrafish (Danio rerio).

Shiozaki, Kazuhiro · 2020

NPY-knockout zebrafish exhibited anxiety-like behaviors with increased brain pomc and avp mRNA levels, demonstrating NPY's anxiolytic role is evolutionarily conserved across vertebrates..

Cholecystokinin in the central nervous system of the sea lamprey Petromyzon marinus: precursor identification and neuroanatomical relationships with other neuronal signalling systems.

Sobrido-Cameán, D · 2020

The sea lamprey CCK-8 peptide is highly similar to mammalian CCK, with CCK neurons distributed across hypothalamus, midbrain, and brainstem regions, and showing the first documented GABA-CCK co-localization in a non-mammalian vertebrate..

Pharmacokinetics, Pharmacodynamics and Drug-Drug Interactions of New Anti-Migraine Drugs-Lasmiditan, Gepants, and Calcitonin-Gene-Related Peptide (CGRP) Receptor Monoclonal Antibodies.

Szkutnik-Fiedler, Danuta · 2020

Gepants and lasmiditan have significant drug interaction potential with CYP3A4 inhibitors, serotonergic drugs, and transporter inhibitors, while CGRP monoclonal antibodies have pharmacodynamic interactions related to immune modulation..

Corticotropin-releasing factor receptor signaling and modulation: implications for stress response and resilience.

Vasconcelos, Mailton · 2020

CRF family peptides and their two receptor subtypes mediate stress responses across multiple organ systems, with dysregulation conferring vulnerability to psychiatric and physical disorders..

Age-related molecular changes in the lumbar dorsal root ganglia of mice: Signs of sensitization, and inflammatory response.

Vincent, Kathleen · 2020

Chronological aging increases CGRP and substance P in lumbar DRG neurons, with concurrent signs of sensitization and inflammation that parallel disc degeneration..

Neuropeptide modulation of central amygdala neuroplasticity is a key mediator of alcohol dependence.

Gilpin, Nicholas W · 2012

The central amygdala (CeA) is a critical brain region where neuropeptides modulate alcohol dependence.

Neuropeptide Y (NPY) in the extended amygdala is recruited during the transition to alcohol dependence.

Gilpin, Nicholas W · 2012

Neuropeptide Y (NPY) in the central amygdala (CeA) plays a critical role in the transition to alcohol dependence.

Ghrelin and dopamine: new insights on the peripheral regulation of appetite.

Abizaid, Alfonso · 2009

Peripheral ghrelin activates mesolimbic dopamine reward pathways (VTA → nucleus accumbens), linking the hunger hormone to food reward and hedonic eating — a gut-brain-dopamine axis connecting appetite to pleasure and potentially to addictive eating behavior..

Ghrelin and other appetite-regulating hormones in paediatric patients with chronic renal failure during dialysis and following kidney transplantation.

Arbeiter, Anja K · 2009

Pediatric CRF patients showed altered ghrelin, PYY3-36, and GLP-1 profiles that changed with dialysis and post-transplant, with appetite hormone disturbances correlating with growth impairment — explaining appetite-growth dysfunction in pediatric kidney disease..

Vagal and hormonal gut-brain communication: from satiation to satisfaction.

Berthoud, H-R · 2008

Post-meal fullness involves two phases: satiation (meal termination via vagal mechanoreception + CCK) and sustained satisfaction (inter-meal fullness via GLP-1, PYY, insulin, leptin) — distinguishing the immediate fullness signal from prolonged appetite suppression for targeted drug development..

Control of hormonal stress reactivity by the endogenous opioid system.

Bilkei-Gorzo, Andras · 2008

Endogenous opioid peptides regulate HPA axis stress reactivity through hypothalamic CRF and ACTH modulation, with opioid system disruption producing altered cortisol responses — explaining stress hormone dysregulation in chronic pain, addiction, and stress disorders..

GPR54 and kisspeptins.

Colledge, W H · 2008

Kisspeptins activate GPR54 receptor to control GnRH neuron firing, serving as the essential gatekeeper for puberty onset and adult fertility — GPR54 mutations cause both absent puberty (hypogonadotropic hypogonadism) and infertility, establishing kisspeptin as the master reproductive switch..

PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation.

Dalmasso, Guillaume · 2008

KPV (Lys-Pro-Val) enters intestinal epithelial cells and immune cells — including macrophages, T cells, and B cells — via the PepT1 peptide transporter.

Anti-inflammatory neuropeptides: a new class of endogenous immunoregulatory agents.

Delgado, Mario · 2008

Anti-inflammatory neuropeptides (VIP, PACAP, alpha-MSH/KPV, CGRP, cortistatin) constitute an endogenous immunoregulatory system: generating regulatory T-cells, suppressing pathogenic Th1/Th17 responses, and promoting inflammation resolution — nature's own anti-inflammatory drug class..

Genetic association of vasoactive intestinal peptide receptor with rheumatoid arthritis: altered expression and signal in immune cells.

Delgado, Mario · 2008

VPAC1 receptor gene polymorphisms were associated with RA susceptibility, with RA patients showing altered VIP receptor expression and signaling — providing genetic evidence linking the neuropeptide anti-inflammatory system to autoimmune disease pathogenesis..

In vivo delivery of lentiviral vectors expressing vasoactive intestinal peptide complementary DNA as gene therapy for collagen-induced arthritis.

Delgado, Mario · 2008

Lentiviral VIP gene delivery to arthritic joints reduced inflammation, cartilage destruction, and bone erosion in collagen-induced arthritis mice — demonstrating neuropeptide gene therapy as a viable approach for local treatment of autoimmune joint disease..

Appetite-related gut peptides, ghrelin, PYY, and GLP-1 in obese women with and without binge eating disorder (BED).

Geliebter, Allan · 2008

Obese women with BED showed distinct postprandial gut peptide profiles (altered ghrelin, PYY3-36, GLP-1) compared to non-binge obese controls, identifying BED-specific gut hormone dysfunction beyond general obesity-related appetite changes..

Postprandial changes in gut regulatory peptides in gastric bypass patients.

Holdstock, C · 2008

Postprandial GLP-1, PYY3-36, and other gut regulatory peptides dramatically increased following gastric bypass, with enhanced hormonal satiety signaling correlating with reduced appetite and caloric intake — hormonal reprogramming, not restriction, as the primary surgical mechanism..

Molecular genetic studies of the arginine vasopressin 1a receptor (AVPR1a) and the oxytocin receptor (OXTR) in human behaviour: from autism to altruism with some notes in between.

Israel, Salomon · 2008

AVPR1a and OXTR genetic polymorphisms are associated with human social behavior variation: autism spectrum features, pair-bonding patterns, empathy levels, and social anxiety — establishing the genetic basis for neuropeptide-mediated social behavior..

The influence of the eradication of Helicobacter pylori on gastric ghrelin, appetite, and body mass index in patients with peptic ulcer disease.

Jang, Eun Jeong · 2008

H.

Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease.

Kannengiesser, K · 2008

In the DSS-colitis model, KPV treatment led to significantly earlier recovery and stronger body weight regain compared to controls (p<0.01).

Effect of protein, fat, carbohydrate and fibre on gastrointestinal peptide release in humans.

Karhunen, L J · 2008

Different macronutrients trigger distinct gut peptide profiles: protein produces the strongest and most diverse satiety peptide response (GLP-1, PYY, CCK); fat strongly triggers CCK/GLP-1; carbohydrate mainly GIP/insulin; fiber enhances GLP-1/PYY through fermentation — macronutrient-specific appetite pharmacology..

Hormone-based therapies in the regulation of fuel metabolism and body weight.

Kesty, Nicole C · 2008

Hormone-based fuel metabolism drugs span GLP-1 agonists (semaglutide class), amylin analogs (pramlintide), PYY analogs, and ghrelin modulators for integrated obesity/diabetes treatment — exploiting endogenous regulatory peptide systems for superior metabolic control..

Structure and function of ghrelin.

Kojima, Masayasu · 2008

Ghrelin's complete structural-functional profile: 28 amino acids with essential octanoyl modification on Ser3, GHS-R1a receptor activation, widespread tissue expression, and validated functions in GH release, appetite, energy homeostasis, and cardiovascular protection..

Acupuncture analgesia: a review of its mechanisms of actions.

Lin, Jaung-Geng · 2008

Acupuncture analgesia mechanisms comprehensively reviewed: frequency-specific endogenous opioid release (low-freq: endorphins/enkephalins; high-freq: dynorphins), serotonergic modulation, spinal gate theory, descending inhibition, and clinical validation — the complete mechanism..

Meal-related changes in ghrelin, peptide YY, and appetite in normal weight and overweight children.

Lomenick, Jefferson P · 2008

Overweight children demonstrated blunted meal-related ghrelin suppression and attenuated PYY3-36 response compared to normal weight peers, indicating childhood obesity involves early-onset gut peptide satiety signaling disruption..

Impact of prosocial neuropeptides on human brain function.

Meyer-Lindenberg, Andreas · 2008

Intranasal oxytocin and vasopressin modulate human social brain circuits (amygdala fear, insula empathy, prefrontal evaluation) as demonstrated by fMRI — neuropeptide modulation of social cognition with therapeutic implications for autism and social anxiety..

The effect of Korean pine nut oil on in vitro CCK release, on appetite sensations and on gut hormones in post-menopausal overweight women.

Pasman, Wilrike J · 2008

Korean pine nut oil stimulated CCK-8 release and reduced appetite desire and prospective food consumption in overweight postmenopausal women (RCT), demonstrating a food-derived natural CCK secretagogue for appetite management..

Oral ingestion of a hydrolyzed gelatin meal in subjects with normal weight and in obese patients: Postprandial effect on circulating gut peptides, glucose and insulin.

Rubio, I G · 2008

Oral gelatin hydrolysate meals stimulated GLP-1, insulin, and glucagon release while suppressing ghrelin in both normal weight and obese subjects, demonstrating collagen peptides trigger satiety hormone responses beyond simple protein-mediated effects..

Endogenous prolactin-releasing peptide regulates food intake in rodents.

Takayanagi, Yuki · 2008

PrRP-deficient mice showed increased food intake and body weight, while PrRP administration reduced feeding, establishing endogenous prolactin-releasing peptide as a novel satiety signal acting through hypothalamic and brainstem appetite circuits..

Vasoactive intestinal peptide-mediated Th17 differentiation: an expanding spectrum of vasoactive intestinal peptide effects in immunity and autoimmunity.

Yadav, Mahesh · 2008

VIP's immunomodulatory spectrum expanded to include Th17 cell regulation: suppressing pathogenic IL-17 producing cells in addition to its established Th1 suppression and Treg promotion — comprehensive anti-autoimmune peptide with Th1/Th17/Treg triple regulation..

Oxytocin improves "mind-reading" in humans.

Domes, Gregor · 2007

Intranasal oxytocin significantly improved performance on the Reading the Mind in the Eyes test in healthy men, demonstrating enhanced social cognition and emotional theory of mind — a distinct cognitive effect beyond anxiety reduction..

Receptor activity-modifying proteins: RAMPing up adrenomedullin signaling.

Gibbons, Carrie · 2007

RAMPs regulate adrenomedullin signaling by modifying calcitonin receptor-like receptor (CLR) specificity: RAMP2/RAMP3 create AM receptors, RAMP1 creates CGRP receptor — explaining how one receptor serves multiple peptide ligands through RAMP partnerships..

Emerging roles of vasoactive intestinal peptide: a new approach for autoimmune therapy.

Gonzalez-Rey, Elena · 2007

VIP generates regulatory T-cells, tolerizes dendritic cells, and suppresses Th1/Th17 inflammatory pathways, providing a comprehensive anti-autoimmune mechanism applicable to rheumatoid arthritis, MS, type 1 diabetes, and transplant rejection..

The role of peptide YY in integrative gut physiology and potential role in obesity.

Grudell, April B M · 2007

PYY integrates multiple gut functions: suppresses appetite (Y2R-mediated), slows gastric emptying, reduces intestinal motility, decreases pancreatic secretion, and promotes fluid absorption — PYY deficiency in obesity contributes to the disordered satiety driving overeating..

A carbohydrate-restricted diet alters gut peptides and adiposity signals in men and women with metabolic syndrome.

Hayes, Matthew R · 2007

Carbohydrate restriction in metabolic syndrome patients modified gut peptide profiles (reduced ghrelin, altered PYY) and adipokine levels (decreased leptin, increased adiponectin), with hormonal changes correlating with weight loss and improved metabolic markers..

Impaired heart contractility in Apelin gene-deficient mice associated with aging and pressure overload.

Kuba, Keiji · 2007

Apelin knockout mice showed impaired cardiac contractility that worsened with aging and pressure overload, definitively establishing apelin as an essential cardiac peptide and a therapeutic target for heart failure and age-related cardiac decline..

Gut hormones as mediators of appetite and weight loss after Roux-en-Y gastric bypass.

le Roux, Carel W · 2007

Enhanced GLP-1 and PYY responses with suppressed ghrelin after RYGB mediated sustained appetite reduction and weight loss, with gut hormone changes persisting years post-surgery — establishing hormonal modification (not just restriction) as the primary mechanism of bariatric success..

Vasoactive intestinal peptide regulates Th17 function in autoimmune inflammation.

Leceta, Javier · 2007

VIP suppressed Th17 cell differentiation and IL-17 production in autoimmune inflammation models, specifically targeting the pathogenic Th17 response that drives rheumatoid arthritis, EAE (MS model), and other autoimmune diseases — precision anti-autoimmune peptide therapy..

Review article: The gastrointestinal tract: neuroendocrine regulation of satiety and food intake.

Maljaars, J · 2007

GI neuroendocrine satiety regulation integrates gut peptide signals (GLP-1, PYY, CCK, oxyntomodulin, ghrelin), enteric neural pathways, and central melanocortin/NPY circuits for comprehensive food intake control — gut peptide drugs leading the obesity treatment pipeline..

Postprandial ghrelin, cholecystokinin, peptide YY, and appetite before and after weight loss in overweight women with and without polycystic ovary syndrome.

Moran, Lisa J · 2007

Weight loss in overweight women modified gut hormone profiles: increased postprandial ghrelin (hunger) and reduced PYY satiety responses — hormonal changes that favor weight regain, explaining the biological basis of yo-yo dieting and weight loss plateau..

Appetite signaling: from gut peptides and enteric nerves to brain.

Näslund, Erik · 2007

The appetite signaling chain: food → gut peptide release (GLP-1, PYY, CCK, ghrelin) → enteric nerve detection → vagal afferent transmission → brainstem integration (NTS) → hypothalamic processing (arcuate) → behavioral output — the complete food-to-decision neural-humoral pathway..

The endocannabinoid system and gut-brain signalling.

Storr, Martin A · 2007

The endocannabinoid system modulates appetite through gut-brain signaling interactions with CCK, GLP-1, ghrelin, and leptin, regulating food intake via vagal afferents and hypothalamic circuits — explaining cannabis appetite effects and informing cannabinoid-gut peptide drug combinations..

Adrenomedullin and endothelial barrier function.

Temmesfeld-Wollbrück, Bettina · 2007

Adrenomedullin maintains endothelial barrier integrity through Rac1-mediated adherens junction stabilization, preventing vascular leak during inflammation — the molecular basis for AM's protective role in sepsis and for AM-targeting therapy (adrecizumab) development..

Upregulation of substance P receptor expression by calcitonin gene-related peptide, a possible cooperative action of two neuropeptides involved in airway inflammation.

Wu, Hong · 2007

Two neuropeptides — Substance P (SP) and CGRP — work together to drive airway inflammation.

The importance of acclimatisation and habituation to experimental conditions when investigating the anorectic effects of gastrointestinal hormones in the rat.

Abbott, C R · 2006

PYY3-36 and GLP-1-mediated appetite suppression required proper mouse acclimatization and habituation to experimental conditions; non-acclimatized mice showed variable, unreliable anorectic responses — explaining conflicting literature results..

Interactions between gut peptides and the central melanocortin system in the regulation of energy homeostasis.

Ellacott, Kate L J · 2006

Peripheral gut peptides (GLP-1, PYY, CCK, ghrelin) converge on the hypothalamic melanocortin system (POMC/AgRP neurons) as the central integration point, with melanocortin neurons serving as the final common pathway translating gut signals into eating behavior..

A novel mechanism for immunosuppression: from neuropeptides to regulatory T cells.

Ganea, Doina · 2006

Neuropeptides including VIP, alpha-MSH/KPV, and CGRP promote immune tolerance through generation of regulatory T cells (Tregs) and suppression of pro-inflammatory dendritic cell activation — a novel immunosuppressive pathway with therapeutic potential for autoimmunity and transplantation..

Apelin: a new plasma marker of cardiopulmonary disease.

Goetze, Jens Peter · 2006

Plasma apelin levels differentiated between cardiac and pulmonary disease causes and provided complementary prognostic information alongside natriuretic peptides — a new peptide biomarker for cardiopulmonary disease characterization..

Adrenomedullin: a tumor progression factor via angiogenic control.

Nakamura, Misa · 2006

Adrenomedullin functions as a tumor progression factor primarily through angiogenesis promotion — stimulating tumor blood vessel formation, supporting cancer growth, and providing a targetable vulnerability for anti-cancer strategies..

Wheat-fibre-induced changes of postprandial peptide YY and ghrelin responses are not associated with acute alterations of satiety.

Weickert, Martin O · 2006

Wheat fiber modified postprandial PYY and ghrelin responses without immediate appetite changes, suggesting fiber-induced gut hormone modulation requires chronic exposure rather than acute meal effects for meaningful appetite impact..

Gut feeling--the secret of satiety?

Bloom, Steve · 2005

Post-prandial gut hormones (GLP-1, PYY, CCK, oxyntomodulin) signal satiety through vagal and bloodstream pathways to brainstem/hypothalamic circuits, with combination peptide mimicry showing greater satiety than single agents — the future of appetite pharmacology..

Evaluation of interactions between CCK and GLP-1 in their effects on appetite, energy intake, and antropyloroduodenal motility in healthy men.

Brennan, Ixchel M · 2005

Combined CCK and GLP-1 infusion produced additive effects on appetite suppression and antropyloroduodenal motility in healthy humans — supporting combination gut peptide therapy for superior satiety and weight management..

The role of corticotropin-releasing factor-like peptides in cannabis, nicotine, and alcohol dependence.

Bruijnzeel, Adrie W · 2005

CRF/urocortin system activation drives the stress/withdrawal component of cannabis, nicotine, and alcohol dependence through CRF1-mediated anxiety during abstinence, creating a negative reinforcement cycle that maintains substance use..

Is there a role for ghrelin and peptide-YY in the pathogenesis of obesity in adults with acquired structural hypothalamic damage?

Daousi, Christina · 2005

Patients with acquired structural hypothalamic damage-induced obesity had elevated ghrelin and reduced PYY3-36 compared to matched controls, suggesting specific gut peptide dysregulation contributes to hypothalamic obesity beyond central appetite circuit damage..

Delayed postprandial gastric emptying and impaired gallbladder contraction together with elevated cholecystokinin and peptide YY serum levels sustain satiety and inhibit hunger in healthy elderly persons.

Di Francesco, Vincenzo · 2005

Morbidly obese patients had delayed gastric emptying, impaired gallbladder contraction, yet elevated CCK and PYY3-36 levels — a paradox suggesting gut satiety signal resistance in obesity, analogous to leptin resistance..

How palatable food disrupts appetite regulation.

Erlanson-Albertsson, Charlotte · 2005

Palatable food disrupts appetite regulation through opioid reward pathway overactivation (hedonic eating), blunted satiety peptide responses (GLP-1, PYY, CCK), and altered ghrelin dynamics — creating a multi-level biological mechanism for food addiction and overconsumption..

Dietary lactitol fermentation increases circulating peptide YY and glucagon-like peptide-1 in rats and humans.

Gee, Jennifer M · 2005

Lactitol colonic fermentation increased circulating PYY and GLP-1 in rats and humans, establishing that short-chain fatty acid production from dietary fiber fermentation stimulates L-cell satiety peptide secretion — a prebiotic mechanism for appetite regulation..

The corticotropin-releasing factor (CRF) family of neuropeptides in inflammation: potential therapeutic applications.

Gravanis, Achille · 2005

CRF family peptides (CRF, urocortin 1-3) modulate peripheral inflammation through CRF1 (generally pro-inflammatory) and CRF2 (generally anti-inflammatory) receptors on immune cells, gut, and skin — with therapeutic applications for IBD, arthritis, and dermatitis..

Peripheral administration of PYY(3-36) produces conditioned taste aversion in mice.

Halatchev, Ilia G · 2005

Peripheral PYY3-36 at appetite-suppressing doses produced conditioned taste aversion (learned food avoidance suggesting nausea), indicating its anorectic effect may partly involve malaise rather than pure satiety — an important consideration for PYY-based obesity drugs..

The pharmacology of DMP696 and DMP904, non-peptidergic CRF1 receptor antagonists.

Li, Yu-Wen · 2005

DMP696 and DMP904 demonstrated CRF1 receptor antagonist anxiolytic activity with distinct pharmacokinetic, selectivity, and efficacy profiles across anxiety models — advancing multiple CRF1 drug candidates with different clinical potential..

Urotensin II in end-stage renal disease: an inverse correlate of sympathetic function and cardiac natriuretic peptides.

Mallamaci, Francesca · 2005

Plasma urotensin II inversely correlated with muscle sympathetic nerve activity and cardiac natriuretic peptides in ESRD patients, suggesting urotensin II serves a counter-regulatory role in the sympathetic-peptide axis in cardiorenal disease..

Glycosylated neuropeptides: a new vista for neuropsychopharmacology?

Polt, Robin · 2005

Glycosylation of opioid and other neuropeptides enhanced BBB penetration, metabolic stability, and analgesic potency after peripheral administration, establishing glycopeptides as a practical strategy for delivering peptide drugs to the brain..

Peptide YY: a potential therapy for obesity.

Renshaw, D · 2005

PYY3-36 reduces food intake through peripheral Y2 receptor-mediated hypothalamic appetite suppression, with clinical development challenges including dose-limiting nausea, route-dependent efficacy, and need for sustained-release formulations..

The role of CRF receptors in anxiety and depression: implications of the novel CRF1 agonist cortagine.

Todorovic, Cedomir · 2005

The novel selective CRF1 agonist cortagine enabled clear dissection of CRF receptor roles: CRF1 activation drives anxiety/depression-like behavior while CRF2 activation promotes stress coping — precise tools for receptor-specific psychiatric drug development..

Adrenomedullin: its role in the cardiovascular system.

Cheung, Bernard M Y · 2004

Adrenomedullin serves as an endogenous cardiovascular protector through vasodilation, cardiac output enhancement, natriuresis, and direct cardioprotection via CRLR/RAMP receptor complexes — a comprehensive cardiovascular defense peptide..

Ghrelin: more than a new frontier in neuroendocrinology.

Ghigo, E · 2004

Ghrelin's biological roles expanded to include immune modulation (anti-inflammatory), reproductive function, cancer cell growth regulation, and cardiovascular protection through GHS-R and non-GHS-R pathways..

The pharmacology of human appetite expression.

Halford, Jason C G · 2004

Human appetite is regulated by a multi-level system including adiposity signals (leptin, insulin), gut peptides (GLP-1, PYY, CCK, ghrelin), and hypothalamic neuropeptides (NPY, AgRP, POMC), with GLP-1 and PYY identified as the most druggable targets..

Peripheral and central signals in the control of eating in normal, obese and binge-eating human subjects.

Hellström, Per M · 2004

Normal, obese, and binge-eating individuals show distinct patterns of appetite signal dysfunction across peripheral (gut peptides, adipokines) and central (hypothalamic neuropeptide) systems — disorder-specific signaling profiles enabling targeted treatment..

The electrophysiology of feeding circuits.

Jobst, Erin E · 2004

Hypothalamic feeding circuits operate through electrophysiological excitation of NPY/AgRP neurons (hunger) and inhibition of POMC/CART neurons (satiety), with peripheral signals (ghrelin, leptin, insulin) directly modulating neuronal firing patterns..

Brain-gut axis and its role in the control of food intake.

Konturek, S J · 2004

Food intake control operates through an integrated brain-gut axis where peripheral peptides (GLP-1, PYY, CCK, ghrelin, amylin) signal via vagal and hormonal routes to central circuits (NPY/AgRP, POMC/CART, CRF) for coordinated appetite regulation..

Molecular evolution of NPY receptor subtypes.

Larhammar, D · 2004

NPY receptor subtypes Y1-Y5 evolved through ancient gene duplications, with each acquiring distinct tissue distribution and functional specialization — Y1 for anxiety/vasoconstriction, Y2 for presynaptic inhibition, Y4 for PP binding, Y5 for feeding..

Gastrointestinal satiety signals II. Cholecystokinin.

Moran, Timothy H · 2004

CCK released by intestinal fat/protein is the primary short-term satiety signal, acting through vagal afferents and brain CCK-A receptors to reduce meal size — the best-characterized gut satiety peptide with therapeutic implications for obesity..

Interactions between NPY and CRF in the amygdala to regulate emotionality.

Sajdyk, Tammy J · 2004

Amygdalar NPY-CRF interactions constitute an anxiety-resilience balance: CRF promotes fear/anxiety through CRF1 while NPY opposes through Y1 receptors — imbalance drives anxiety disorders, PTSD, and addiction..

Biology of eating behavior in obesity.

Schwartz, Gary J · 2004

Eating behavior in obesity reflects disrupted multi-level peptide signaling: blunted gut satiety peptides (GLP-1, PYY, CCK), altered opioid reward processing, ghrelin dysregulation, and impaired central neuropeptide circuits — biology driving behavioral excess..

Gut hormones as peripheral anti obesity targets.

Small, Caroline J · 2004

Peripheral gut hormone-based obesity drug development focuses on GLP-1 agonists (most advanced), PYY analogs, oxyntomodulin, amylin analogs, and PP as practical anti-obesity drug targets with established physiological rationale and clinical precedent..

Identification of an Adrenomedullin precursor fragment in plasma of sepsis patients.

Struck, Joachim · 2004

A mid-regional pro-adrenomedullin (MR-proADM) fragment was identified and quantified in sepsis patient plasma, providing a stable, measurable surrogate for the unstable mature adrenomedullin — establishing the basis for clinical MR-proADM sepsis testing..

Gastric pacing for morbid obesity: plasma levels of gastrointestinal peptides and leptin.

Cigaina, Valerio · 2003

Gastric pacing in morbidly obese patients altered circulating CCK, somatostatin, and leptin levels, providing a neuroendocrine mechanism for the satiety and weight loss effects of this device..

Actions of neuropeptide Y and growth hormone secretagogues in the arcuate nucleus and ventromedial hypothalamic nucleus.

Kumarnsit, Ekkasit · 2003

GH secretagogues primarily activated arcuate nucleus neurons while NPY activated both arcuate and ventromedial hypothalamic neurons, demonstrating distinct appetite-stimulating circuits despite similar feeding outcomes..

Stress responsive neurohormones in depression and anxiety.

Ströhle, A · 2003

Depression, panic, and PTSD show distinct stress neurohormone patterns (CRF, vasopressin, NPY alterations), with ANP demonstrating anxiolytic properties — disorder-specific peptide profiles enabling targeted therapy..

Ghrelin promotes slow-wave sleep in humans.

Weikel, J C · 2003

Intravenous ghrelin administration increased slow-wave sleep (deep sleep) across the total night and enhanced delta-wave activity during the second half of the night.

Adrenomedullin and cancer.

Zudaire, E · 2003

Adrenomedullin is overexpressed in many cancers where it promotes tumor growth, drives angiogenesis (tumor blood vessel formation), and may suppress anti-tumor immunity — positioning it as a multi-mechanism cancer therapy target..

The CRF peptide family and their receptors: yet more partners discovered.

Dautzenberg, Frank M · 2002

Expanded CRF peptide family including urocortins reveals distinct CRF1 (anxiety/depression) and CRF2 (stress coping/appetite/cardiovascular) receptor functions, enabling receptor-specific drug development..

Adrenomedullin has multiple roles in disease stress: development and remission of the inflammatory response.

Elsasser, Ted H · 2002

Adrenomedullin acts as both a pro-inflammatory stress responder and an anti-inflammatory tissue protector during disease, with its dual nature and temporal dynamics determining whether it helps or harms at each stage..

Involvement of cholecystokinin/gastrin-related peptides and their receptors in clinical gastrointestinal disorders.

Jensen, Robert T · 2002

CCK/CCK-A receptor dysfunction is implicated in gallbladder and pancreatic diseases, while gastrin/CCK-B receptor abnormalities may contribute to GI cancer development, positioning these peptide systems as therapeutic targets..

Cell and molecular biology of the multifunctional peptide, adrenomedullin.

López, José · 2002

Adrenomedullin functions as a vasodilator, growth regulator, neurotransmitter, anti-inflammatory agent, and hormone modulator through CRLR/RAMP receptor complexes, with therapeutic implications across cardiovascular, inflammatory, and neoplastic diseases..

Comparison of plasma levels of mature adrenomedullin and natriuretic peptide as markers of cardiac function in hemodialysis patients with coronary artery disease.

Osajima, Akihiko · 2002

Mature adrenomedullin and BNP provided complementary cardiac information in hemodialysis patients: BNP reflected LV dysfunction more specifically, while mAM reflected broader cardiovascular status including vascular and renal components..

Corticotropin-releasing factor receptors 1 and 2 in anxiety and depression.

Reul, Johannes M H M · 2002

CRF1 promotes anxiety and depression while CRF2 may have opposing anxiolytic/stress-recovery effects, with urocortins as natural CRF2-preferring ligands enabling receptor-specific therapeutic targeting..

Peripheral signals conveying metabolic information to the brain: short-term and long-term regulation of food intake and energy homeostasis.

Havel, P J · 2001

Appetite regulation involves two integrated time scales: acute meal-by-meal gut peptide signals (CCK, GLP-1, ghrelin, PYY) and chronic body weight signals (leptin, insulin), converging on hypothalamic and brainstem integration centers..

The role of adrenomedullin in producing differential hemodynamic responses during sepsis.

Koo, D J · 2001

Adrenomedullin contributes to both phases of sepsis: beneficial vasodilation during early compensation and harmful cardiovascular collapse during late decompensation, driven by progressive ADM accumulation from reduced clearance and increased tissue production..

The gut and food intake: an update for surgeons.

Näslund, E · 2001

Gut peptides (ghrelin, CCK, GLP-1, PYY) regulate appetite through neural and hormonal pathways that are significantly disrupted by gastrointestinal surgery, requiring surgical awareness for optimal patient management..

The small intestine is an important source of adrenomedullin release during polymicrobial sepsis.

Zhou, M · 2001

Small intestinal ADM mRNA and protein were significantly upregulated during polymicrobial sepsis, with the gut releasing ADM into portal circulation, establishing the intestine as a major source of circulating ADM during sepsis..

Neuropeptide Y promotes sleep and inhibits ACTH and cortisol release in young men.

Antonijevic, I A · 2000

Intranasal NPY promoted sleep and reduced ACTH and cortisol in healthy young men, demonstrating CRH-opposing anxiolytic and sedative effects with potential therapeutic applications for depression and insomnia..

Afferent signals regulating food intake.

Bray, G A · 2000

Food intake regulation involves convergent afferent signals from gut peptides (CCK, GLP-1, PYY, ghrelin), adipose tissue (leptin), vagal mechanoreceptors, and higher brain centers, all integrated by hypothalamic circuitry..

Adrenomedullin: a new peptidergic regulator of the vascular function.

Minamino, N · 2000

Adrenomedullin dilates blood vessels through dual mechanisms — direct smooth muscle relaxation and endothelial NO release — with autocrine/paracrine production by vascular endothelial and smooth muscle cells..

Plasma neuropeptide-Y concentrations in humans exposed to military survival training.

Morgan, C A · 2000

Special forces soldiers showed higher plasma NPY during extreme stress and faster post-stress recovery compared to regular troops, with higher NPY correlating with better performance and less psychological distress..

Recent advances with the CRF1 receptor: design of small molecule inhibitors, receptor subtypes and clinical indications.

McCarthy, J R · 1999

Non-peptide CRF1 receptor antagonists selectively block stress signaling and show anxiolytic and antidepressant effects in animal models, with potential clinical applications spanning anxiety, depression, addiction, and inflammation..

The nonpeptide growth hormone secretagogue, MK-0677, activates hypothalamic arcuate nucleus neurons in vivo.

Bailey, A R · 1998

MK-0677 induced c-Fos expression in arcuate nucleus neurons in vivo, confirming direct hypothalamic activation as a mechanism for its GH-releasing effect..

Loss of bombesin-induced feeding suppression in gastrin-releasing peptide receptor-deficient mice.

Hampton, L L · 1998

GRP-R knockout mice completely lost bombesin-induced feeding suppression, demonstrating that GRP-R is the key receptor mediating this satiety signal..

How does treatment influence endocrine mechanisms in acute severe heart failure? Effects on cardiac natriuretic peptides, the renin system, neuropeptide Y and catecholamines.

Missouris, C G · 1998

Treatment of acute severe heart failure reduced BNP and ANP levels but not catecholamines or renin-angiotensin activity, indicating natriuretic peptides more accurately reflect clinical improvement..

Life without neuropeptide Y.

Palmiter, R D · 1998

NPY knockout mice had normal appetite and body weight but showed dramatically increased susceptibility to seizures and excitotoxicity, revealing NPY's primary role as an endogenous anticonvulsant..

Proadrenomedullin-derived peptides.

Samson, W K · 1998

Adrenomedullin and PAMP are co-produced from the same gene but lower blood pressure through distinct mechanisms (direct vascular vs.

Electroacupuncture: mechanisms and clinical application.

Ulett, G A · 1998

Low-frequency (2 Hz) electroacupuncture activates endorphin/enkephalin systems (mu/delta receptors), while high-frequency (100 Hz) activates dynorphin systems (kappa receptors), with combined frequencies providing additive analgesia..

Hypothalamic targets for growth hormone secretagogues.

Robinson, I C · 1997

GH secretagogues activate hypothalamic neurons and require an intact GHRH system for full in vivo potency, despite being able to release GH directly from the pituitary..

Neurobiology of corticotropin releasing factor (CRF) receptors and CRF-binding protein: implications for the treatment of CNS disorders.

Behan, D P · 1996

Three CRF receptor subtypes (CRF1, CRF2alpha, CRF2beta) and a CRF-binding protein coordinate stress responses, and newly developed non-peptide CRF antagonists show therapeutic promise..

Increased circulating adrenomedullin, a novel vasodilatory peptide, in sepsis.

Hirata, Y · 1996

Plasma adrenomedullin concentrations were extremely elevated in septic ICU patients compared to healthy controls, correlating with disease severity..

The growth hormone-releasing peptide KP-102 induces c-fos expression in the arcuate nucleus.

Kamegai, J · 1996

KP-102 induces c-fos expression specifically in the arcuate nucleus, and this occurs even in hypophysectomized rats, confirming a direct hypothalamic site of action..

The therapeutic potential of neuropeptide Y. Analgesic, anxiolytic and antihypertensive.

Munglani, R · 1996

NPY mediates analgesia and hyperalgesia through distinct receptor subtypes, alongside established roles in blood pressure regulation and anxiety modulation..

Intracerebroventricular orphanin FQ/nociceptin suppresses dopamine release in the nucleus accumbens of anaesthetized rats.

Murphy, N P · 1996

Orphanin FQ/nociceptin suppressed dopamine release in the nucleus accumbens, acting opposite to classical opioids which typically increase dopamine in this reward-related region..

Endogenous opioid peptides in parasympathetic, sympathetic and sensory nerves in the guinea-pig heart.

Steele, P A · 1996

Approximately 40% of cardiac ganglion cells contained dynorphin A immunoreactivity, and opioid peptides were found in parasympathetic, sympathetic, and sensory cardiac nerves..

Palatability-induced hyperphagia increases hypothalamic Dynorphin peptide and mRNA levels.

Welch, C C · 1996

Ad libitum access to a high-fat/sucrose diet significantly increased hypothalamic dynorphin peptide and mRNA levels compared to standard diet, suggesting opioid peptide-mediated overeating..

Opioid and anti-opioid peptides.

Cesselin, F · 1995

The review synthesizes opioid peptide pharmacology including the novel concept of anti-opioid peptides that counterbalance opioid effects and may drive tolerance..

Central actions of peptide and non-peptide growth hormone secretagogues in the rat.

Dickson, S L · 1995

Both GHRP-6 and non-peptide GH secretagogues activated Fos expression in the arcuate nucleus and excited arcuate neuroendocrine neurons, confirming central brain actions..

Nitrous oxide selectively releases Met5-enkephalin and Met5-enkephalin-Arg6-Phe7 into canine third ventricular cerebrospinal fluid.

Finck, A D · 1995

Nitrous oxide selectively increased met-enkephalin and met-enkephalin-Arg-Phe in third ventricular CSF without affecting beta-endorphin, leu-enkephalin, or dynorphin..

Regulation of cholecystokinin secretion by intraluminal releasing factors.

Liddle, R A · 1995

Intraluminal peptide factors, released in response to dietary proteins and fats, are key regulators of CCK secretion that coordinate digestion..

The effects of morphine treatment and morphine withdrawal on the dynorphin and enkephalin systems in Sprague-Dawley rats.

Nylander, I · 1995

Chronic morphine increased dynorphin A and B in the nucleus accumbens and met-enkephalin in the striatum, with distinct withdrawal-phase patterns across brain regions..

Opioids and sexual behavior of male rats: involvement of the medial preoptic area.

van Furth, W R · 1995

Beta-endorphin in the MPOA dose-dependently impaired male rat sexual behavior, prevented by naloxone, while other opioid peptides were less effective at equivalent doses..

Effect of sulpiride or paroxetine on cerebrospinal fluid neuropeptide concentrations in patients with chronic tension-type headache.

Bach, F W · 1994

Sulpiride decreased CSF met-enkephalin while paroxetine increased it in chronic tension headache patients after 8 weeks of treatment..

Difference between plasma N- and C-terminally directed beta-endorphin immunoreactivity in infantile autism.

Leboyer, M · 1994

The N-terminal to C-terminal beta-endorphin ratio was significantly different in children with autism compared to healthy controls and children with Rett syndrome..

Palatability of a meal influences release of beta-endorphin, and of potential regulators of food intake in healthy human subjects.

Melchior, J C · 1994

A highly palatable meal significantly increased post-meal beta-endorphin, pancreatic polypeptide, and neurotensin compared to the same unpalatable meal..

Opioid peptides in the pituitary: a hormone, a paracrine modulator and a peptide in search of a function.

Schäfer, M K · 1994

Each opioid precursor family has a distinct role in the pituitary: beta-endorphin as a hormone, dynorphin as a paracrine modulator of oxytocin, and enkephalins as yet-uncharacterized players..

Intrahypothalamic neuroendocrine actions of corticotropin-releasing factor.

Almeida, O F · 1993

CRF fibers terminate within the hypothalamus and directly modulate the release of growth hormone, gonadotropins, and opioid peptides through local synaptic connections..

Endogenous opioid-like substances in perinatal asphyxia and cerebral injury due to anoxia.

Cao, L · 1993

Plasma and CSF levels of all three opioid peptides were elevated in asphyxiated newborns vs.

Lead toxicity and alterations in opioid systems.

Kitchen, I · 1993

Lead exposure alters brain opioid peptide concentrations and receptor binding across multiple brain regions, potentially explaining neurological toxicity symptoms..

CSF neuropeptides in cancer pain: effects of spinal opioid therapy.

Samuelsson, H · 1993

Cancer pain patients had altered CSF neuropeptide profiles.

Effects of delta sleep-inducing peptide on sleep of chronic insomniac patients. A double-blind study.

Bes, F · 1992

In this double-blind trial, delta sleep-inducing peptide (DSIP) showed some objective sleep improvements in chronic insomniacs — higher sleep efficiency and shorter time to fall asleep compared to placebo.

Neuropeptides and inflammatory bowel disease.

Eysselein, V E · 1991

VIP is diminished in intestinal smooth muscle of Crohn's patients.

Neuropeptides.

Moore, M R · 1991

32 brain peptides are categorized and reviewed across location, synthesis, receptor binding, and function, organized into opioid, pituitary hormone, and miscellaneous peptide groups..

N-terminal degradation of low molecular weight opioid peptides in human cerebrospinal fluid.

Benter, I F · 1990

Aminopeptidase M in human CSF degrades opioid peptides at rates inversely proportional to chain length.

The effects of opioid peptides on dopamine release in the nucleus accumbens: an in vivo microdialysis study.

Spanagel, R · 1990

Mu and delta opioids increase, while kappa opioids decrease, dopamine release in the nucleus accumbens.

Opioid-like immunoreactive neurons in secretomotor pathways of the guinea-pig ileum.

Steele, P A · 1990

All submucous neurons in guinea pig ileum are immunoreactive for prodynorphin peptides.

Regulation of striatonigral prodynorphin peptides by dopaminergic agents.

Trujillo, K A · 1990

Both amphetamine (dopamine agonist) and haloperidol (dopamine antagonist) significantly altered levels of prodynorphin peptides in the striatum, substantia nigra, and hippocampus..

Stimulation of endogenous opioid release displaces mu receptor binding in rat hippocampus.

Wagner, J J · 1990

Physiological-like high-frequency stimulation of opioid-containing pathways releases detectable amounts of endogenous opioids in hippocampal slices.

The neuroendocrine paraventricular hypothalamus: receptors, signal transduction, mRNA and neurosecretion.

Lightman, S L · 1988

Endogenous opioid peptides inhibit the release of both vasopressin and oxytocin from the posterior pituitary.

Study of delta sleep-inducing peptide efficacy in improving sleep on short-term administration to chronic insomniacs.

Monti, J M · 1987

Delta sleep-inducing peptide (DSIP) administered intravenously at 25 nmol/kg over four nights showed some improvements in sleep metrics in chronic insomniacs — including reduced awakenings, decreased waking time, and increased total sleep time — but these changes were not statistically significant compared to placebo.

Comparative Analysis of Pioglitazone and Tirzepatide on Body Weight, Glucose Levels, Neuroinflammation, and Oxidative Stress in Diabetic Rats.

Alhowail, Ahmad · 2025

Comparative analysis of pioglitazone and tirzepatide on body weight and glucose shows tirzepatide superior for weight loss while both effectively lower blood sugar through different mechanisms..

Efficacy of GLP-1 Agonists in Psychiatric Illnesses: A Scoping Review.

Ali, Mohsan · 2025

Scoping review of GLP-1 agonist efficacy in psychiatric illnesses covers schizophrenia, depression, bipolar disorder, and addiction, finding emerging evidence for metabolic and possibly direct neuropsychiatric benefits..

Neuropeptide Y mRNA expression in the aging inferior colliculus of fischer brown norway rats.

Almassri, Laila S · 2025

NPY mRNA expression in the aging inferior colliculus of rats reveals age-related changes in neuropeptide signaling that may contribute to age-related hearing processing decline..

Ineffectiveness of tirzepatide in mitigating Doxorubicin-induced oxidative stress and cognitive deficits in a rat model.

Alolayan, Salma A · 2025

Tirzepatide was ineffective at mitigating doxorubicin-induced oxidative stress and cardiotoxicity, suggesting not all GLP-1/GIP drug protective effects extend to chemotherapy damage..

A novel therapeutic prospect: a dual-acting tirzepatide for Alzheimer's disease.

Alshehri, Ghadah H · 2025

Review of tirzepatide's dual GLP-1/GIP mechanism explores therapeutic prospects across diabetes, obesity, NASH, cardiovascular disease, and emerging indications..

Tirzepatide: a novel therapeutic approach for Alzheimer's disease.

Alshehri, Ghadah H · 2025

Review proposes tirzepatide as a novel therapeutic approach for Alzheimer's disease through dual GLP-1/GIP neuroprotective mechanisms targeting neuroinflammation and metabolic dysfunction..

Analysis of bisphenol A-modulated expression of hypothalamic thyroid, estrogen, and peroxisome proliferator-activated receptors and concurrent mitochondrial dynamics following short-term exposure in mice.

Alymbaeva, Daiana · 2025

Bisphenol A modulated hypothalamic NPY and melanocortin neuropeptide expression, revealing a mechanism by which this common chemical disrupts appetite regulation and metabolic health..

Exogenous oral application of PYY and exendin-4 impacts upon taste-related behavior and taste perception in wild-type mice.

Iyer, Satya · 2025

Using adeno-associated virus vectors to deliver PYY and exendin-4 encoding genes to the salivary glands of wild-type male mice, researchers found that oral presence of these satiety peptides significantly altered taste-related behavioral responsiveness across multiple taste qualities.

Ubrogepant, erenumab, and eptinezumab antagonize positive inotropic effects of the calcitonin gene-related peptide in the isolated human atrium.

Neumann, Joachim · 2025

Three anti-migraine drugs that target the CGRP pathway — ubrogepant, erenumab, and eptinezumab — also reduce the force of heart contraction in isolated human atrial tissue at therapeutic concentrations.

Characteristics and management of headache among psychiatric outpatients at a Japanese general hospital: A retrospective study with an exploratory CGRP case series.

Otani, Kyohei · 2025

14.3% of psychiatric outpatients had headache diagnoses, with the majority managed within psychiatry departments rather than neurology..

Bromelain Improves Hypothalamic Control of Energy Homeostasis in High-Fat Diet-Induced Obese Rats.

Ozen Koca, Raviye · 2025

Bromelain restored GLUT2 and normalized POMC and IGF1R expression in hypothalamic tissue of obese rats..

Antinociceptive and neuromodulatory effects of the scorpion venom tetrapeptide tetrascorpin-1 in a long-lasting pain hypersensitivity model in mice.

Pagano, Salvatore · 2025

Intranasal AaTs-1 significantly reduced pain hypersensitivity and neuroinflammation while preventing morpho-functional alterations in spinal cord neurons and glial cells in a formalin-induced chronic pain model..

Selective Receptor Modulation by Truncated Neuropeptide Y (3-36) Dissociates Vasoconstriction from Neuroprotection in Experimental Glaucoma.

Palanivel, Viswanthram · 2025

Truncated NPY (3-36) selectively activated neuroprotective pathways (via Y2/Y5 receptors) while avoiding vasoconstriction (mediated by Y1 receptors), demonstrating that receptor-selective peptide analogs can dissociate beneficial from harmful effects in glaucoma treatment..

Easy-to-Engineer Flexible Nanoelectrode Sensor from an Inexpensive Overhead Projector Sheet for Sweat Neuropeptide-Y Detection.

Aerathupalathu Janardhanan, Jayakrishnan · 2024

Researchers built an inexpensive, flexible biosensor from a common overhead projector (OHP) sheet that can detect Neuropeptide Y (NPY) in sweat with remarkable sensitivity.

Neuro- and vasoprotective potential of neuropeptide Y Y2 receptor agonist, NPY13-36, against transient focal cerebral ischemia in spontaneously hypertensive rats.

Przykaza, Łukasz · 2024

NPY13-36 was injected directly into the brain during either the ischemic phase (while blood flow was blocked) or the reperfusion phase (when blood flow returned).

Intermittent Fasting Targets Osteocyte Neuropeptide Y to Relieve Osteoarthritis.

Qian, Yu-Xuan · 2024

Osteocytes (the most common bone cells) secreted excess neuropeptide Y during osteoarthritis.

Evaluating a Venom-Bioinspired Peptide, NOR-1202, as an Antiepileptic Treatment in Male Mice Models.

Quintanilha, Maria Varela Torres · 2024

NOR-1202 showed route-dependent antiepileptic effects.

Human RAMP1 overexpressing mice are resistant to migraine therapies for motion sensitivity.

Rahman, Shafaqat M · 2024

The nestin/hRAMP1 mice showed heightened sensitivity to CGRP's effects at lower doses compared to normal mice.

Migraine inhibitor olcegepant reduces weight loss and IL-6 release in SARS-CoV-2-infected older mice with neurological signs.

Rahman, Shafaqat M · 2024

Older mice (over 18 months, roughly equivalent to elderly humans) infected with mouse-adapted SARS-CoV-2 showed neurological symptoms including fever, dizziness, and nausea in two wild-type strains (C57BL/6J and 129/SvEv). Olcegepant treatment protected against the permanent weight loss seen after infection.

Neurokinin B Administration Induces Dose Dependent Proliferation of Seminal Vesicles in Adult Rats.

Ramzan, Muhammad Haris · 2024

Neurokinin B at three doses (1 μg, 1 ng, and 10 pg) administered intraperitoneally for 12 days increased seminal vesicle weight, epithelial height, and seminal fructose levels in a dose-dependent manner.

The impact of the migraine treatment onabotulinumtoxinA on inflammatory and pain responses: Insights from an animal model.

Reducha, Philip Victor · 2024

CFA-induced facial inflammation increased periorbital mechanical sensitivity.

Prenatal ethanol and cannabis exposure have sex- and region-specific effects on somatostatin and neuropeptide Y interneurons in the rat hippocampus.

Reid, Hannah M O · 2024

Prenatal THC exposure had region-specific and sex-specific effects on inhibitory interneurons in the hippocampus: - Female-specific decrease in NPY neuron density in the CA1 region after THC exposure - Somatostatin neurons were altered by THC in a region-specific and sex-specific manner - Combined alcohol + THC: reduced NPY neurons in the ventral dentate gyrus - Co-exposure did NOT produce additive or synergistic effects in other hippocampal areas These findings build on the group's previous work showing prenatal substance exposure alters parvalbumin interneurons, extending the picture to two additional inhibitory cell types..

Lineage-tracing reveals an expanded population of NPY neurons in the inferior colliculus.

Silveira, Marina A · 2024

Lineage-tracing revealed a larger population of NPY neurons in the inferior colliculus than expression-tracking alone, and optogenetic experiments confirmed these neurons form local inhibitory synaptic circuits..

Cocaine- and Amphetamine-Regulated Transcript Peptide in the Central Nervous System of the Gecko, Hemidactylus leschenaultii: Molecular Characterization, Neuroanatomical Organization, and Regulation by Neuropeptide Y.

Singh, Omprakash · 2024

CART neuropeptide was characterized for the first time in a reptilian brain (gecko), showing >93% similarity to mammalian CART peptides and regulation by NPY via Y1 receptors in the hypothalamic arcuate nucleus..

'The effect of neuropeptide Y1 receptor agonist on hypothalamic neurogenesis in rat experimental depression model'.

Solak, Hatice · 2024

NPY Y1 receptor agonist treatment increased hypothalamic NPY gene expression and improved active swimming behavior in the forced swim test in chronically stressed rats, while depression alone decreased expression of IGF1R, FGF2, POMC, NPY, and GLUT2 genes..

Multiomics analysis of canine myocardium after circumferential pulmonary vein ablation: Effect of neuropeptide Y on long-term reinduction of atrial fibrillation.

Song, Qiyuan · 2024

Multi-omics profiling identified NPY as significantly downregulated after pulmonary vein ablation.

Substance P promotes transforming growth factor-β-induced collagen synthesis in human corneal fibroblasts.

Sugioka, Koji · 2024

Substance P had no independent effect on corneal fibroblast collagen synthesis or MMP-1 expression.

ABCA7-dependent induction of neuropeptide Y is required for synaptic resilience in Alzheimer's disease through BDNF/NGFR signaling.

Tayran, Hüseyin · 2024

ABCA7 loss suppresses neuropeptide Y expression, reducing BDNF and synaptic density — a mechanism directly linking this Alzheimer's risk gene to brain resilience through NPY-BDNF-NGFR signaling..

Mechanistic study of acupuncture on the pterygopalatine ganglion to improve allergic rhinitis: analysis of multi-target effects based on bioinformatics/network topology strategie.

Tian, Meihui · 2024

Acupuncture at the pterygopalatine ganglion decreased serum substance P and elevated neuropeptide Y in allergic rhinitis rats, with effects mediated through TLR4/NF-kB/NLRP3 pathway inhibition..

Perspective role of Substance P in Amyotrophic Lateral Sclerosis: From neuronal vulnerability to neuroprotection.

Tirassa, Paola · 2024

Elevated BNP and NT-proBNP levels in diabetes patients correlate with cardiac abnormalities and can be used for heart failure risk stratification and potentially for guiding treatment strategies..

Neuropeptides regulate embryonic salivary gland branching through the FGF/FGFR pathway in aging klotho-deficient mice.

Toan, Nguyen Khanh · 2024

Substance P and neuropeptide Y regulated embryonic salivary gland branching morphogenesis through the FGF/FGFR pathway in klotho-deficient accelerated aging mice..

The effect of prenatal fumonisin B exposure on bone innervation in newborn Wistar rats.

Tomaszewska, Ewa · 2024

Prenatal fumonisin B exposure disrupted neuropeptide-containing bone nerve networks, decreasing galanin and VIP-positive fibers in both dose groups while paradoxically increasing overall network complexity at the higher dose..

Ghrelin Induces the Production of Hypothalamic NPY Through the AMPK-mTOR Pathway to Alleviate Cancer-induced Bone Pain.

Xu, Longjie · 2024

Ghrelin activated the hypothalamic AMPK-mTOR pathway to induce NPY production, alleviating cancer-induced bone pain in rats.

Nppb contributes to Sepsis-Induced myocardial injury by regulating Senescence-Related genes.

Yang, Hang · 2024

Heart-specific Nppb knockout improved sepsis-induced myocardial injury in mice.

Loss of Function of Vasoactive-intestinal Peptide Alters Sex Ratio and Reduces Male Reproductive Fitness in Zebrafish.

Yu, Yang · 2024

VIPa knockout males had 70% fewer spermatids, 80% reduced fertilization capacity, 50% lower sperm motility, and near-absent sexual motivation due to downregulation of androgen synthesis enzymes and decreased 11-ketotestosterone production..

The effect of SP/NK1R on expression and activity of glutaredoxin and thioredoxin proteins in prostate cancer cells.

Zarei Shandiz, Sara · 2024

Substance P/NK1R signaling increased ROS and decreased both the expression and activity of glutaredoxin and thioredoxin in PC3 and LNCaP prostate cancer cells.

Visual stimulation and brain-derived neurotrophic factor (BDNF) have protective effects in experimental autoimmune uveoretinitis.

Zloh, Miloslav · 2024

Visual stimulation increased retinal BDNF levels and provided neuroprotective effects against retinal cell degeneration..

Chronic oral nicotine administration and withdrawal regulate the expression of neuropeptide Y and its receptors in the mesocorticolimbic system.

Birdogan, Ali · 2021

Nicotine withdrawal (24-48h) dramatically increased NPY and receptor (Y1, Y2, Y5) mRNA levels across the mesocorticolimbic system, suggesting NPY signaling upregulation as a compensatory response to withdrawal-induced negative affect..

The potential anti-inflammatory and anti-nociceptive effects of rat hemopressin (PVNFKFLSH) in experimental arthritis.

Camargo, Livia L · 2021

Hemopressin reduced arthritis-induced joint swelling, pain behavior, and inflammatory markers (MPO, leukocytes, IL-6) via both intra-articular and oral routes, independent of CGRP and substance P..

Research on Correlation Between Psychological Factors, Mast Cells, and PAR-2 Signal Pathway in Irritable Bowel syndrome.

Chao, Guanqun · 2021

IBS-D patients showed downregulated NPS, NPY, and NPY2R alongside increased mast cell activation and PAR-2 expression, suggesting mast cell-driven neuropeptide changes link gut inflammation to psychological symptoms..

Substance P restores spermatogenesis in busulfan-treated mice: A new strategy for male infertility therapy.

Chen, Zhihong · 2021

Substance P at 5 nmol/kg restored spermatogenesis in busulfan-treated azoospermic mice by stimulating spermatogonia proliferation via NK1R-ERK1/2 signaling..

Ninjinyoeito improves anxiety behavior in neuropeptide Y deficient zebrafish.

Kawabe, Momoko · 2021

NYT suppressed anxiety behaviors in NPY-KO zebrafish after 4-day dietary supplementation, with reduced tyrosine hydroxylase and ERK phosphorylation in brain.

Lessons from Wolfram Syndrome: Initiation of DDAVP Therapy Causes Renal Salt Wasting Due to Elevated ANP/BNP Levels, Rescued by Fludrocortisone Treatment.

Kleanthous, Kleanthis · 2021

DDAVP initiation in untreated Wolfram DI caused ANP elevation ×50 and BNP ×2-4, blocking zona glomerulosa steroidogenesis, causing secondary mineralocorticoid deficiency and acute hyponatremia from RSW.

Mechanism of Immunoregulatory Properties of Vasoactive Intestinal Peptide in the K/BxN Mice Model of Autoimmune Arthritis.

Leceta, Javier · 2021

VIP is proposed to treat RA by: (1) inhibiting T cell plasticity toward non-classic Th1 cells, (2) enhancing follicular regulatory T cell (Tfr) activity, and (3) consequently reducing systemic pathogenic autoantibody titers that drive arthritis..

Refractoriness to drugs in migraine may be the result of developing anti-drug antibodies.

Maselis, K · 2021

Refractory migraine may result from anti-drug antibody development against biologic treatments including anti-CGRP monoclonal antibodies.

Neuropathological explanation of minimal COVID-19 infection rate in newborns, infants and children - a mystery so far. New insight into the role of Substance P.

Mehboob, Riffat · 2021

The authors hypothesize that age-dependent differences in Substance P (SP) levels explain why children rarely develop severe COVID-19 while elderly patients suffer the worst outcomes.

Pathophysiologic mechanisms of itch in bullous pemphigoid.

Hashimoto, Takashi · 2020

Itch severity in bullous pemphigoid correlates with eosinophils, substance P, neurokinin 1 receptor, IL-31 signaling, IL-13, periostin, and basophils, while mast cells and TRPV1 were not significantly correlated..

Overexpression of TIMP3 inhibits discogenic pain by suppressing angiogenesis and the expression of substance P in nucleus pulposus.

He, Mingwei · 2020

Inflammation reduced TIMP3 expression in nucleus pulposus (NP) cells, the cells at the center of spinal discs.

The substance P and neurokinin-1 receptor system in human thyroid cancer: an immunohistochemical study.

Isorna, Inmaculada · 2020

Both Substance P (SP) and the neurokinin-1 receptor (NK-1R) were expressed in all thyroid tissue, normal and cancerous.

Teriparatide improves pain-related behavior and prevents bone loss in ovariectomized mice.

Kato, Sho · 2020

Teriparatide prevents ovariectomy-induced bone loss, reduces mechanical hyperalgesia, and suppresses CGRP and TRPV1 upregulation in dorsal root ganglion neurons innervating affected limbs..

Acute and Repeated Intranasal Oxytocin Differentially Modulate Brain-wide Functional Connectivity.

Pagani, Marco · 2020

Acute intranasal oxytocin focally enhanced limbic connectivity, while repeated 7-day dosing caused widespread brain connectivity reconfiguration with paradoxical reduction in social behavior..

Functional Connectomic Approach to Studying Selank and Semax Effects.

Panikratova, Ya R · 2020

Both Selank and Semax modulated functional connectivity between right amygdala and right temporal cortex regions (fusiform, inferior/middle temporal, parahippocampal gyri) with both shared and peptide-specific effects..

Free Fatty Acid-Induced Peptide YY Expression Is Dependent on TG Synthesis Rate and Xbp1 Splicing.

Paton, Chad M · 2020

Free fatty acids induce PYY via Xbp1 activation in L-cells, but triglyceride re-esterification rate determines signal duration — chronic high-fat diets accelerate re-esterification and blunt PYY response..

Immediate inhibition of spinal secretory phospholipase A2 prevents the pain and elevated spinal neuronal hyperexcitability and neuroimmune regulatory genes that develop with nerve root compression.

Quindlen-Hotek, Julia C · 2020

Immediate intrathecal sPLA2 inhibition after C7 nerve root compression prevented mechanical allodynia, attenuated dorsal horn hyperexcitability, restored normal neuronal classification, and reduced mGluR5, substance P, IL1α, and IL1β gene expression to sham levels..

Stress-related endogenous neuropeptides induce neuronal excitation in the Laterodorsal Tegmentum.

Romero-Leguizamón, Cesar R · 2020

Urocortin and CRF produce pre- and postsynaptic excitatory effects on LDT cholinergic neurons through CRFR1 receptors, recruiting MAPK/ERK and SERCA-ATPase pathways..

Resolvin E1 Inhibits Substance P-Induced Potentiation of TRPV1 in Primary Sensory Neurons.

Jo, Youn Yi · 2016

Resolvin E1 (RvE1), a molecule derived from omega-3 fatty acids, blocked the ability of substance P — a key pain-signaling neuropeptide — to amplify TRPV1 pain receptor activity in mouse sensory neurons.

The opioid peptide beta-endorphin stimulates acrosome reaction in human spermatozoa.

Urizar-Arenaza, I · 2016

Beta-endorphin, an opioid peptide known for pain relief and mood regulation, also triggers the acrosome reaction in human sperm — a critical step required for fertilization.

Vasoactive intestinal peptide-deficient mice exhibit reduced pathology in trinitrobenzene sulfonic acid-induced colitis.

Abad, Catalina · 2015

When TNBS-induced colitis (a model for Crohn's disease) was triggered in VIP knockout mice, they showed a milder clinical profile compared to wild-type mice.

Protective effects of the neuropeptide PACAP in diabetic retinopathy.

Szabadfi, Krisztina · 2012

The neuropeptide PACAP (pituitary adenylate cyclase activating polypeptide) significantly protected the retina from diabetes-induced damage when injected into the eyes of diabetic rats.

Protein hydrolysates induce CCK release from enteroendocrine cells and act as partial agonists of the CCK1 receptor.

Foltz, Martin · 2008

Protein hydrolysates directly stimulated CCK secretion from STC-1 enteroendocrine cells and showed partial CCK1 receptor agonist activity, demonstrating dual mechanisms: dietary peptides both trigger satiety hormone release AND directly activate satiety receptors..

The impact of postnatal environment on opioid peptides in young and adult male Wistar rats.

Gustafsson, Lisa · 2008

Postnatal environment quality produced lasting changes in brain opioid peptide levels (dynorphin, enkephalin) across development into adulthood in Wistar rats, demonstrating enduring early-life programming of the opioid system that may predispose to later psychopathology..

Immunoregulatory properties of vasoactive intestinal peptide in human T cell subsets: implications for rheumatoid arthritis.

Gutiérrez-Cañas, Irene · 2008

VIP differentially modulated human T-cell subsets: suppressed CD4+ effector T-cell proliferation/activation while supporting CD4+CD25+ regulatory T-cell function and survival — directly applicable to restoring the effector/regulatory T-cell balance in rheumatoid arthritis..

Involvement of spinal Met-enkephalin in nicotine-induced antinociception in mice.

Kiguchi, Norikazu · 2008

Nicotine antinociception involved spinal met-enkephalin release confirmed by intrathecal anti-met-enkephalin antibody blocking, extending the drug-endogenous opioid amplification mechanism to nicotine — explaining some of smoking's pain-modifying effects..

Chronic psychosocial stress affects corticotropin-releasing factor in the paraventricular nucleus and central extended amygdala as well as urocortin 1 in the non-preganglionic Edinger-Westphal nucleus of the tree shrew.

Kozicz, T · 2008

Chronic psychosocial stress produced CRF alterations in the PVN and central amygdala correlating with increased anxiety-like behavior, mapping how chronic social stress reprograms the brain's CRF stress system to produce persistent anxiety..

Effects of acute ethanol on opioid peptide release in the central amygdala: an in vivo microdialysis study.

Lam, Minh P · 2008

In-vivo microdialysis showed acute ethanol directly triggered beta-endorphin and met-enkephalin release in the central amygdala, providing real-time evidence for alcohol's emotional/anxiolytic effects through local opioid peptide release in the brain's fear center..

Association of pro-ghrelin and GHS-R1A gene polymorphisms and haplotypes with heavy alcohol use and body mass.

Landgren, Sara · 2008

Pro-ghrelin and GHS-R1A gene polymorphisms and haplotypes were associated with heavy alcohol use and BMI in humans, providing genetic evidence linking the ghrelin system to both alcohol addiction vulnerability and body weight regulation..

Catalytic antibody degradation of ghrelin increases whole-body metabolic rate and reduces refeeding in fasting mice.

Mayorov, Alexander V · 2008

A ghrelin-degrading catalytic antibody (ghrelin-ase) increased metabolic rate and reduced post-fast refeeding in mice, demonstrating an immunological approach to ghrelin neutralization for obesity treatment — antibody-based appetite suppression..

PYY3-36 injection in mice produces an acute anorexigenic effect followed by a delayed orexigenic effect not observed with other anorexigenic gut hormones.

Parkinson, James R C · 2008

PYY3-36 injection produced biphasic appetite response: acute anorexia followed by delayed orexigenic rebound, unlike GLP-1 which showed sustained anorexia — this rebound effect may limit PYY3-36's obesity drug potential compared to GLP-1 agonists..

Molecular recognition of corticotropin-releasing factor by its G-protein-coupled receptor CRFR1.

Pioszak, Augen A · 2008

CRF-CRFR1 molecular recognition involves a two-step binding model: C-terminal CRF helix binds the receptor N-terminus (affinity), then N-terminal CRF contacts the receptor core (activation) — structural basis for designing CRF receptor-selective drugs..

Gastric motor effects of ghrelin and growth hormone releasing peptide 6 in diabetic mice with gastroparesis.

Qiu, Wen-Cai · 2008

Ghrelin and GHRP-6 restored gastric contractile activity and emptying in diabetic gastroparesis mice, with effects mediated through smooth muscle and neural pathways — confirming GH secretagogues as gastroprokinetic agents for diabetic GI dysfunction..

Therapeutic effects of ghrelin and growth hormone releasing peptide 6 on gastroparesis in streptozotocin-induced diabetic guinea pigs in vivo and in vitro.

Qiu, Wen-cai · 2008

Ghrelin and GHRP-6 restored gastric emptying in streptozotocin-diabetic rats with gastroparesis, improving gastric motility through GHS-R activation — validating GH secretagogues as therapeutic agents for diabetic gastroparesis, a common and debilitating complication..

Modulatory effect of ghrelin in prepubertal porcine ovarian follicles.

Rak, A · 2008

Ghrelin modulated steroidogenesis (progesterone, estradiol) and cell proliferation in prepubertal porcine ovarian follicles, establishing a direct ovarian ghrelin system with implications for reproductive development and fertility..

The vasoactive intestinal peptide gene is a key modulator of pulmonary vascular remodeling and inflammation.

Said, Sami I · 2008

VIP gene expression was essential for normal pulmonary vascular regulation, with VIP knockout mice developing spontaneous pulmonary hypertension and vascular remodeling — establishing VIP as an endogenous protective factor against pulmonary vascular disease..

Possible involvement of dynorphin A release via mu1-opioid receptor on supraspinal antinociception of endomorphin-2.

Sakurada, Shinobu · 2008

Supraspinal endomorphin-2 antinociception involved dynorphin A release mediated by mu-1 receptors in the brain, with anti-dynorphin antibodies partially blocking the effect — confirming endomorphin-2's unique dual-pathway (mu + dynorphin) analgesic mechanism..

Postulated role of vasoactive neuropeptide-related immunopathology of the blood brain barrier and Virchow-Robin spaces in the aetiology of neurological-related conditions.

Staines, D R · 2008

Autoimmune targeting of vasoactive neuropeptides (VIP, PACAP) at blood-brain barrier Virchow-Robin spaces may impair cerebral blood flow autoregulation and promote neuroinflammation — a novel immunopathological theory for neurodegenerative diseases..

Are multiple sclerosis and amyotrophic lateral sclerosis autoimmune disorders of endogenous vasoactive neuropeptides?

Staines, Donald R · 2008

Autoimmune attack on endogenous vasoactive neuropeptides (VIP, PACAP, CGRP) is proposed as a pathogenic mechanism for MS and ALS, with detection of anti-neuropeptide antibodies and correlation with disease activity — neuropeptide autoimmunity as neurodegeneration cause..

Does autoimmunity of endogenous vasoactive neuropeptides cause retinopathy in humans?

Staines, Donald R · 2008

Autoimmune targeting of vasoactive neuropeptides (VIP, PACAP) in retinal vessels may cause retinopathy through impaired local blood flow autoregulation — proposing neuropeptide autoimmunity as a mechanism for vascular retinal diseases including diabetic retinopathy..

Detection of a novel immunoreactive endomorphin 2-like peptide in rat brain extracts.

Szemenyei, Erzsébet · 2008

A novel endomorphin-2-like immunoreactive peptide was detected in rat brain extracts with different chromatographic properties from known endomorphin-2, potentially representing a new endogenous mu-opioid peptide or modified form — expanding the endogenous opioid catalog..

Antinociception produced by 14,15-epoxyeicosatrienoic acid is mediated by the activation of beta-endorphin and met-enkephalin in the rat ventrolateral periaqueductal gray.

Terashvili, Maia · 2008

14,15-Epoxyeicosatrienoic acid (EET) produced antinociception mediated by beta-endorphin and met-enkephalin release (confirmed by antisera blocking), establishing a lipid mediator → endogenous opioid peptide → pain relief signaling cascade..

Stimulatory and suppressive signal transduction regulates vasoactive intestinal peptide receptor-1 (VPAC-1) in primary mouse CD4 T cells.

Vomhof-DeKrey, Emilie E · 2008

VPAC-1 receptor on macrophages was upregulated by pro-inflammatory signals (LPS, IFN-γ) and downregulated by anti-inflammatory signals (IL-10, TGF-β) — dynamic receptor regulation that adapts VIP anti-inflammatory sensitivity to the inflammatory microenvironment..

TCR signaling and environment affect vasoactive intestinal peptide receptor-1 (VPAC-1) expression in primary mouse CD4 T cells.

Vomhof-DeKrey, Emilie E · 2008

CD4 T-cell VPAC-1 receptor expression was regulated by TCR activation strength and cytokine milieu (IL-2, IL-7, IL-15), determining VIP immunomodulatory sensitivity — explaining context-dependent neuropeptide-immune regulation at the T-cell level..

Nociceptin/orphanin FQ blocks the antinociception induced by mu, kappa and delta opioid agonists on the cold water tail-flick test.

Chen, Xiaohong · 2007

Nociceptin/OFQ blocked spinal antinociception from mu (DAMGO), kappa (U50,488H), and delta (DPDPE) opioid agonists in the cold water tail-flick test, confirming nociceptin as a universal anti-opioid peptide opposing all three opioid receptor systems..

Organization of endogenous opioids in the rostral agranular insular cortex of the rat.

Evans, Joshua M · 2007

Immunohistochemical mapping revealed distinct laminar distributions of met-enkephalin, dynorphin, and beta-endorphin in the rostral agranular insular cortex — the brain's emotional pain processing region — providing the opioid peptide architecture for pain affect modulation..

Ethanol-induced effects on opioid peptides in adult male Wistar rats are dependent on early environmental factors.

Gustafsson, L · 2007

Ethanol-induced changes in brain opioid peptides (dynorphin, enkephalin) in adult Wistar rats were modulated by early postnatal environment (maternal separation), demonstrating gene × early environment interaction programming adult opioid system alcohol sensitivity..

Interaction of apolipoprotein AIV with cholecystokinin on the control of food intake.

Lo, Chun Min · 2007

ApoAIV enhanced CCK-mediated satiety signaling for synergistic food intake reduction in rats, with the interaction involving CCK-A receptor pathways — demonstrating cooperation between lipid transport proteins and gut peptides for integrated appetite control..

The nootropic and neuroprotective proline-containing dipeptide noopept restores spatial memory and increases immunoreactivity to amyloid in an Alzheimer's disease model.

Ostrovskaya, Rita U · 2007

Noopept (proline-containing dipeptide) restored spatial memory in brain-lesioned rats and increased hippocampal BDNF immunoreactivity, establishing BDNF upregulation as the neurotrophic mechanism for Noopept's cognitive-enhancing and neuroprotective activities..

Gastric/intestinal electrical stimulation modulates appetite regulatory peptide hormones in the stomach and duodenum in rats.

Xu, Junying · 2007

Gastric/intestinal electrical stimulation modulated local expression of appetite peptides (ghrelin, CCK, PYY) in the gut wall of obese rats, demonstrating that neurostimulation devices directly reprogram local gut peptide production for appetite modification..

The existence of opioid receptors in the cochlea of guinea pigs.

Jongkamonwiwat, Nopporn · 2006

All three opioid receptor types (mu, delta, kappa) were demonstrated in the guinea pig cochlea by RT-PCR, immunohistochemistry, and autoradiography, establishing the complete molecular basis for opioid peptide signaling in the auditory system..

Peptide YY (PYY)3-36 modulates thyrotropin secretion in rats.

Oliveira, K J · 2006

PYY3-36 modulated thyrotropin (TSH) secretion in rats through hypothalamic/pituitary pathways, revealing a novel gut peptide-thyroid axis connection — the satiety system influences thyroid function beyond just appetite control..

Orexigenic effects of a growth hormone secretagogue and nitric oxide in aged rats and dogs: correlation with the hypothalamic expression of some neuropeptidergic/receptorial effectors mediating food intake.

Rigamonti, Antonello E · 2006

GH secretagogue orexigenic effects were attenuated in aged rats and dogs, correlating with reduced hypothalamic GHS-R expression — age-related decline in receptor density blunts the appetite-stimulating side effect, potentially beneficial for elderly GHS therapy..

Arginine vasopressin enhances periaqueductal gray synthesis and secretion of enkephalin and endorphin in the rat.

Yang, Jun · 2006

Arginine vasopressin stimulated enkephalin and endorphin synthesis and secretion in the periaqueductal gray, demonstrating vasopressin-opioid peptide cross-talk in the brain's primary descending pain modulation center..

Only arginine vasopressin, not oxytocin and endogenous opiate peptides, in hypothalamic paraventricular nucleus play a role in acupuncture analgesia in the rat.

Yang, Jun · 2006

Only arginine vasopressin (not oxytocin or endogenous opioid peptides) in the paraventricular nucleus mediated electroacupuncture-induced analgesia — demonstrating pathway specificity where different brain nuclei use different peptide systems for the same analgesic effect..

Through central arginine vasopressin, not oxytocin and endogenous opiate peptides, glutamate sodium induces hypothalamic paraventricular nucleus enhancing acupuncture analgesia in the rat.

Yang, Jun · 2006

MSG-induced hypothalamic analgesia was mediated through central AVP signaling exclusively, with oxytocin and opioid peptide antagonists having no effect — confirming vasopressin's dominance in hypothalamic pain modulation pathways..

Regulative effects of ovarian steroids on rat gastric motility and sensitivity.

Yang, Xia · 2006

Ovarian steroids (estrogen, progesterone) regulated gastric motility patterns and visceral sensitivity in rats, providing the hormonal mechanism for menstrual cycle-related GI symptom variations experienced by many women..

Modulation of cardiovascular excitatory responses in rats by transcutaneous magnetic stimulation: role of the spinal cord.

Zhou Yi Syuu, Wei · 2006

Transcutaneous magnetic stimulation modulated cardiovascular excitatory responses through spinal cord mechanisms involving opioid peptide and nociceptin pathways — establishing a non-invasive approach to modulating cardiovascular autonomic reflexes..

Inhibitory effects on intake of cholecystokinin-8 and cholecystokinin-33 in rats with hepatic proper or common hepatic branch vagal innervation.

Eisen, S · 2005

Both CCK-8 and CCK-33 reduced food intake through hepatic branch vagal afferents in rats, but CCK-33 produced more sustained satiety — demonstrating shared pathway with temporal differences between CCK molecular forms..

Increased CRF-like and NPY-like immunoreactivity in adult rats exposed to nicotine during adolescence: relation to anxiety-like and depressive-like behavior.

Slawecki, Craig J · 2005

Adolescent nicotine exposure produced lasting increases in CRF-like and NPY-like immunoreactivity in amygdala and hypothalamic stress regions in adult rats, correlating with increased anxiety — adolescent nicotine permanently alters brain stress peptide systems..

The somatostatin subtype-2 receptor antagonist, BIM-23627, improves the catabolic effects induced by long-term glucocorticoid treatment in the rat.

Tulipano, Giovanni · 2005

Somatostatin subtype-2 receptor antagonist BIM-23627 partially reversed glucocorticoid-induced catabolism in rats by reducing somatostatin's GH-inhibitory tone, improving GH/IGF-1 axis activity and reducing muscle and bone loss from chronic steroids..

Mitochondria-targeted peptide prevents mitochondrial depolarization and apoptosis induced by tert-butyl hydroperoxide in neuronal cell lines.

Zhao, Kesheng · 2005

SS-31, a cell-permeable peptide targeting the inner mitochondrial membrane, prevented mitochondrial depolarization and apoptosis in neuronal cells exposed to oxidative stress — demonstrating precision subcellular peptide targeting for protecting the cell's energy source..

Peptide YY3-36 inhibits food intake in mice through a melanocortin-4 receptor-independent mechanism.

Halatchev, Ilia G · 2004

PYY3-36 inhibited food intake in MC4R knockout mice, demonstrating a melanocortin-4 receptor-independent satiety mechanism and establishing PYY as an independent appetite-suppressing pathway from the alpha-MSH system..

Distribution of methionine and leucine enkephalin neurons within the social behavior circuitry of the male Syrian hamster brain.

Holt, Avril Genene · 2004

Met- and leu-enkephalin immunoreactive neurons were distributed throughout social behavior brain nuclei (BNST, medial amygdala, MPOA, lateral septum, PAG) in male hamsters, providing an anatomical framework for opioid peptide regulation of social and reproductive behaviors..

Maternal separation alters maternal care, but has minor effects on behavior and brain opioid peptides in adult offspring.

Marmendal, Maarit · 2004

Maternal separation significantly altered maternal care patterns but produced only subtle changes in adult offspring brain opioid peptides and behavior, suggesting compensatory mechanisms partially buffer against early-life adversity effects..

Structure-activity studies on the corticotropin releasing factor antagonist astressin, leading to a minimal sequence necessary for antagonistic activity.

Rijkers, Dirk T S · 2004

SAR studies on astressin identified the minimal CRF antagonist sequence retaining biological activity at both CRF1 and CRF2 receptors, advancing design of smaller, more drug-like peptide antagonists for stress-related psychiatric disorders..

Acute effects of PYY3-36 on food intake and hypothalamic neuropeptide expression in the mouse.

Challis, B G · 2003

Peripheral PYY3-36 acutely suppressed food intake and altered hypothalamic neuropeptide expression (decreased NPY, increased POMC) in mice, confirming it as a gut-derived satiety signal that modulates central appetite gene programs..

Selank and short peptides of the tuftsin family in the regulation of adaptive behavior in stress.

Kozlovskaya, M M · 2003

Selank and tuftsin-family peptides improved adaptive behavior in stressed animals in a phenotype-dependent manner, with different peptides optimal for different emotional reactivity types — supporting personalized peptide anxiolytic therapy..

Downregulation of glucocorticoid receptors of liver cytosols and the role of the inflammatory cytokines in pathological stress in scalded rats.

Liu, Du-hu · 2002

Pathological burn stress downregulated liver glucocorticoid receptors through inflammatory cytokine (TNF-α, IL-1, IL-6) action, explaining cortisol resistance and uncontrolled inflammation during severe trauma..

GH-releasing peptide-2 increases fat mass in mice lacking NPY: indication for a crucial mediating role of hypothalamic agouti-related protein.

Tschöp, Matthias · 2002

GHRP-2 increased fat mass in NPY knockout mice, demonstrating that GH secretagogue-induced adiposity is mediated by hypothalamic AgRP rather than NPY, identifying a critical alternative pathway for ghrelin's metabolic effects..

Impaired prohormone convertases in Cpe(fat)/Cpe(fat) mice.

Berman, Y · 2001

CPE-fat mice showed impaired prohormone convertase activity resulting in defective processing of opioid peptides (prodynorphin, proenkephalin) and other peptide hormones, linking peptide processing dysfunction to obesity..

Growth hormone secretagogue activation of the arcuate nucleus and brainstem occurs via a non-noradrenergic pathway.

Bailey, A R · 2000

Chemical ablation of noradrenergic neurons did not prevent GH secretagogue-induced Fos expression in the arcuate nucleus or brainstem, demonstrating a non-noradrenergic activation pathway..

The effect on opioid peptides in the rat brain, after chronic treatment with the anabolic androgenic steroid, nandrolone decanoate.

Johansson, P · 2000

Chronic nandrolone treatment altered met-enkephalin and dynorphin concentrations in limbic and striatal brain regions, providing a neurochemical mechanism for steroid-associated mood and behavioral disturbances..

ARC POMC mRNA and PVN alpha-MSH are lower in obese relative to lean zucker rats.

Kim, E M · 2000

Obese Zucker rats had reduced arcuate POMC mRNA and PVN alpha-MSH levels compared to lean controls, indicating impaired melanocortin satiety signaling as a driver of genetic obesity..

Coordinated Up-regulation by hypoxia of adrenomedullin and one of its putative receptors (RDC-1) in cells of the rat blood-brain barrier.

Ladoux, A · 2000

Hypoxia induced coordinated upregulation of adrenomedullin and its receptor RDC-1 in brain astrocytes and endothelial cells, with NF-κB-mediated transcriptional activation, suggesting an autocrine/paracrine protective mechanism at the blood-brain barrier..

CCK peptides with combined features of hexa- and tetrapeptide CCK-A agonists.

Pierson, M E · 2000

Hybrid CCK-A agonist peptides combining structural features of hexapeptide and tetrapeptide classes showed potent receptor binding and selectivity, advancing design of satiety-inducing peptide drugs for obesity..

Basal levels and alcohol-induced changes in nociceptin/orphanin FQ, dynorphin, and enkephalin levels in C57BL/6J mice.

Ploj, K · 2000

Alcohol-preferring mice had lower baseline nociceptin and dynorphin B in reward regions, with alcohol consumption producing additional changes in met-enkephalin levels, linking opioid/nociceptin system configuration to alcohol preference..

Central changes in nociceptin dynorphin B and Met-enkephalin-Arg-Phe in different models of nociception.

Rosén, A · 2000

Neuropathic and inflammatory chronic pain models produced distinct regional patterns of nociceptin, dynorphin B, and met-enkephalin changes in brain pain pathways, indicating pain type-specific opioid system plasticity..

Chronic central infusion of growth hormone secretagogues: effects on fos expression and peptide gene expression in the rat arcuate nucleus.

Bailey, A R · 1999

Chronic central GH secretagogue infusion upregulated NPY and GHRH gene expression in the arcuate nucleus while altering Fos expression patterns, demonstrating neuroplastic adaptations to sustained receptor stimulation..

GHRP-6-induced changes in electrical activity of single cells in the arcuate, ventromedial and periventricular nucleus neurones [correction of nuclei] of a hypothalamic slice preparation in vitro.

Hewson, A K · 1999

GHRP-6 excited most arcuate nucleus neurons but had mixed excitatory/inhibitory effects in ventromedial and periventricular hypothalamic nuclei, revealing multi-circuit brain modulation by GH secretagogues..

STZ-induced diabetes decreases and insulin normalizes POMC mRNA in arcuate nucleus and pituitary in rats.

Kim, E M · 1999

STZ-induced diabetes decreased POMC mRNA by significant amounts in the hypothalamic arcuate nucleus and anterior pituitary by 2-4 weeks, with insulin treatment (3 weeks) normalizing expression levels..

Activation of arcuate nucleus neurons by systemic administration of leptin and growth hormone-releasing peptide-6 in normal and fasted rats.

Luckman, S M · 1999

Leptin and GHRP-6 activate different populations of arcuate nucleus neurons, with limited overlap, indicating independent pathways for fat-derived and peptide-stimulated growth hormone regulation..

Pulmonary clearance of adrenomedullin is reduced during the late stage of sepsis.

Ornan, D A · 1999

Pulmonary clearance of adrenomedullin was significantly reduced during late-stage sepsis in rats, contributing to ADM accumulation and the hemodynamic collapse of septic shock..

Endogenous dynorphins: possible role in peripheral tinnitus.

Sahley, T L · 1999

Endogenous dynorphins in the inner ear interact with NMDA receptors to modulate auditory nerve excitability, and dysregulation of this system may contribute to tinnitus and hyperacusis by altering spontaneous neural activity..

Adrenomedullin is upregulated in the heart and aorta during the early and late stages of sepsis.

Zhou, M · 1999

Adrenomedullin was locally upregulated in cardiac and aortic endothelial and smooth muscle cells during both early (hyperdynamic) and late (hypodynamic) sepsis stages, establishing cardiovascular tissue as a primary source..

Cerebrospinal fluid vasopressin levels: correlates with aggression and serotonin function in personality-disordered subjects.

Coccaro, E F · 1998

Cerebrospinal fluid levels of arginine vasopressin (AVP) were directly correlated with life history of general aggression and aggression against persons in people with personality disorders.

The growth hormone secretagogue KP-102-induced stimulation of food intake is modified by fasting, restraint stress, and somatostatin in rats.

Shibasaki, T · 1998

KP-102 stimulated food intake in freely-fed but not fasted or stressed rats, and central somatostatin administration blocked this effect, demonstrating state-dependent appetite modulation by GH secretagogues..

The peptide orphanin FQ inhibits beta-endorphin neurons and neurosecretory cells in the hypothalamic arcuate nucleus by activating an inwardly-rectifying K+ conductance.

Wagner, E J · 1998

Orphanin FQ inhibited 68% of arcuate nucleus neurons, including beta-endorphin cells and neurosecretory neurons, through activation of inwardly-rectifying potassium conductance, providing a cellular mechanism for its anti-opioid effects..

Attenuation of the growth hormone secretagogue induction of Fos protein in the rat arcuate nucleus by central somatostatin action.

Dickson, S L · 1997

Octreotide (somatostatin analog) attenuated GH secretagogue-induced Fos expression in the arcuate nucleus, showing somatostatin opposes GHRP action centrally..

Gastrointestinal peptide hormones in acute viral hepatitis.

Budillon, G · 1996

Multiple gastrointestinal peptide hormone levels were significantly altered during acute hepatic cytonecrosis and returned toward normal during liver regeneration..

Pituitary-adrenal activity and opioid release in ponies during thiopentone/halothane anaesthesia.

Luna, S P · 1995

Anesthesia triggered release of endogenous opioids, ACTH, vasopressin, cortisol, and catecholamines, with constant higher halothane producing more cardiovascular depression..

High-performance liquid chromatographic resolution of synthetic opiate and "anti-opiate" peptides from human plasma.

Partilla, J S · 1995

Single HPLC method achieved over 80% recovery of multiple opioid and anti-opioid peptides from human plasma in one analytical run..

Age-related mu-, delta-and kappa-opioid ligands in respiratory-related brain regions of piglets: effect of prenatal cocaine.

Zhang, C · 1995

Opioid peptide levels in respiratory brainstem regions change significantly between young and older piglets, and prenatal cocaine exposure disrupts this developmental pattern..

Opioid modulation of oxytocin release from spinal cord synaptosomes.

Daddona, M M · 1994

Naloxone (5 micromolar) enhanced potassium-evoked oxytocin release from spinal cord synaptosomes, showing tonic opioid inhibition of spinal oxytocin..

Prodynorphin-derived peptide expression in primate cortex and striatum.

Healy, D J · 1994

Alpha-neo-endorphin was the dominant prodynorphin peptide in primate brain, with striatal concentrations significantly exceeding cortical levels across all four peptides..

Behavioral effects of systemically administered mu and kappa opioid agonists in the squirrel monkey: peptides versus alkaloids.

Jones, D N · 1994

Peptide opioid agonists (DAMGO, dynorphin analog) were less potent than corresponding non-peptide agonists (morphine, U50,488) in modifying monkey behavior after intramuscular injection..

Plasticity in spinal opioid control of lower urinary tract function in paraplegic cats.

Thor, K B · 1994

Naloxone restored urinary function in chronic spinal cats but not acute ones, demonstrating opioid system plasticity that contributes to urinary retention after spinal cord injury..

Immunocytochemical evidence for the presence of Met-enkephalin and Leu-enkephalin in distinct neurons in the brain of the elasmobranch fish Scyliorhinus canicula.

Vallarino, M · 1994

Both met-enkephalin and leu-enkephalin are present in separate neuron populations in the dogfish shark brain, but dynorphin-related peptides were not detected..

Opioid peptide gene expression in the nucleus tractus solitarius of rat brain and increases induced by unilateral cervical vagotomy: implications for role of opioid neurons in respiratory control mechanisms.

Rutherfurd, S D · 1993

Proenkephalin and prodynorphin mRNA found in NTS and other medullary nuclei.

Mu- and delta-opioid receptors inhibitorily linked to dopamine-sensitive adenylate cyclase in rat striatum display a selectivity profile toward endogenous opioid peptides different from that of presynaptic mu, delta and kappa receptors.

Schoffelmeer, A N · 1993

Post-synaptic mu/delta receptors inhibiting DA-stimulated adenylate cyclase showed different endogenous peptide affinity profiles than presynaptic mu, delta, and kappa receptors..

Spinal involvement of both dynorphin A and Met-enkephalin in the antinociception induced by intracerebroventricularly administered bremazocine but not morphine in the mouse.

Tseng, L F · 1993

Spinal dynorphin A and met-enkephalin mediate bremazocine's pain relief but not morphine's, showing distinct opioid signaling pathways..

Receptor-selective opioid peptides fail to affect behavioral responses induced by a low dose of apomorphine in the mouse.

Ukai, M · 1993

Receptor-selective opioid peptides (DAMGO, dynorphin A, DPLPE) had no effect on low-dose apomorphine-induced behavioral suppression..

Influence of opioids on CSF vasopressin concentration in newborn pigs.

Armstead, W M · 1992

Topical dynorphin(1-13) dilated pial arteries during normotension but constricted them during hypotension.

Central effects of tumor necrosis factor alpha and interleukin-1 alpha on nociceptive thresholds and spontaneous locomotor activity.

Bianchi, M · 1992

Central TNF-alpha and IL-1-alpha both increased nociceptive thresholds.

Delta and kappa opiate receptors in primary astroglial cultures. Part II: Receptor sets in cultures from various brain regions and interactions with beta-receptor activated cyclic AMP.

Eriksson, P S · 1992

Delta and kappa opioid receptors were co-localized on astroglia from cortex, striatum, and brainstem.

Detection of prodynorphin end products in lizard, turtle, and alligator brain extracts.

Goldsmith, A M · 1992

All four prodynorphin end products detected in turtle, lizard, and alligator brains by radioimmunoassay and chromatography..

Beta-endorphin processing and cellular origins in rat spinal cord.

Gutstein, Howard B · 1992

Beta-endorphin and POMC processing products were found in rat spinal cord cells, suggesting local production beyond supraspinal sources..

Hippocampal opioid peptides and seizures.

Hong, J S · 1992

Both seizure types caused initial opioid release.

Vasoactive intestinal polypeptide induces neurogenic contraction of guinea-pig ileum. Involvement of acetylcholine and substance P.

Katsoulis, S · 1992

VIP (20 nM-1 microM) induced neurogenic gut contractions via acetylcholine and substance P.

Tachykinin systems in the spinal cord and basal ganglia: influence of neonatal capsaicin treatment or dopaminergic intervention on levels of peptides, substance P-encoding mRNAs, and substance P receptor mRNA.

Sivam, S P · 1992

Capsaicin reduced spinal SP and NKA without changing NK1 receptor mRNA.

Characterization of the release of Met-enkephalin from isolated nerve terminals: release kinetics and cation-dependence.

Verhage, M · 1992

Met-enkephalin release from synaptosomes was calcium-dependent with distinct kinetics.

Naltrexone-sensitizing effects of centrally administered morphine and opioid peptides.

Adams, J U · 1991

Acute central opioid pretreatment produces rapid sensitization to naltrexone, predominantly through mu receptors.

Opioids in cerebrospinal fluid in hypotensive newborn pigs.

Armstead, W M · 1991

Hemorrhagic hypotension raised brain fluid opioid levels and caused pial artery dilation in newborn pigs.

Opioid peptides in Parkinson's disease: effects of dopamine repletion.

Baronti, F · 1991

Cerebrospinal fluid MERGL levels were significantly low in Parkinson's patients after overnight medication withdrawal.

Central peptidergic neurons as targets for glucocorticoid action. Evidence for the presence of glucocorticoid receptor immunoreactivity in various types of classes of peptidergic neurons.

Cintra, A · 1991

Glucocorticoid receptors were found in opioid peptide neurons and other peptidergic neurons, with strong regional variation across the brain..

Characterization of opioid-sensitive neurons in the anteroventral third ventricle region of polydipsic inbred mice in vitro.

Hattori, Y · 1991

Morphine inhibited 44% of AV3V neurons in polydipsic STR/N mice vs.

Neuropeptide regulation of feeding in dogs.

Inui, A · 1991

Pancreatic polypeptides and dynorphin A stimulated feeding in satiated dogs.

Evidence for enkephalin- and endorphin-immunoreactive cells in the anterior pituitary of the axolotl Ambystoma mexicanum.

Leon-Olea, M · 1991

Leu-enkephalin immunoreactivity was found in many cells of the axolotl anterior pituitary, unlike mammals.

The phylogeny of Met-enkephalin and Leu-enkephalin: studies on the holostean fish Lepisosteus platyrhincus and the Australian lungfish, Neoceratodus forsteri.

McDonald, L K · 1991

Authentic met-enkephalin and leu-enkephalin were detected in holostean fish and lungfish brains.

Effect of opioid peptides on electrically evoked acetylcholine release from Torpedo electromotor neurons.

Oron, L · 1991

Dynorphin A(1-8) approximately doubled acetylcholine release from Torpedo electromotor neurons.

Increased methionine-enkephalin levels in genetically epileptic (tg/tg) mice.

Patel, V K · 1991

Met-enkephalin was significantly elevated in cortex, hippocampus, and brainstem of tg/tg epileptic mice.

The prenatal development profile of expression of opioid peptides and receptors in the mouse brain.

Rius, R A · 1991

All three opioid peptide classes (enkephalin, dynorphin, endorphin) were detected in embryonic mouse brain before their putative receptors during E11.5 to P1..

Effects of opioid be drugs on auditory evoked potentials suggest a role of lateral olivocochlear dynorphins in auditory function.

Sahley, T L · 1991

Kappa opioid agonists enhanced auditory nerve compound action potential amplitudes.

Effects of PCB (Aroclor 1254) on non-specific immune parameters in rhesus (Macaca mulatta) monkeys.

Tryphonas, H · 1991

Chronic low-dose PCB exposure increased serum complement and NK cell activity while altering other immune parameters in rhesus monkeys..

Prostanoids modulate opioid cerebrovascular responses in newborn pigs.

Armstead, W M · 1990

Opioid peptides have differential effects on neonatal cerebral vasculature: enkephalins dilate, beta-endorphin constricts, and dynorphin switches depending on blood pressure status.

Effects of intracerebroventricular injection of dynorphin, leumorphin and alpha neo-endorphin on operant feeding in pigs.

Baldwin, B A · 1990

Full-length dynorphin A (1-17 or 1-13), leumorphin, and alpha-neo-endorphin induced rapid feeding in pigs.

Immunohistochemistry of opioid peptides in the guinea pig endocrine pancreas.

Cetin, Y · 1990

All three opioid peptide families are present in the guinea pig endocrine pancreas but in different cell types, with processing pathways distinct from other organs..

Expression of vasopressin and opiates but not of oxytocin genes studied by in situ hybridization in embryonic rat brain primary cultures.

Di Scala-Guenot, D · 1990

Prodynorphin and proenkephalin genes are expressed in 16-day embryonic rat brain cultures, earlier than previously known.

Formation of [Leu5]enkephalin from dynorphin A(1-8) by rat central nervous tissue in vitro.

Dixon, D M · 1990

Dynorphin A(1-8) is extensively converted to leu-enkephalin by metalloendopeptidase EC 3.4.24.15 across all brain regions, effectively switching opioid signaling from kappa to delta receptors..

Regulation of dopamine release in vitro from the posterior pituitary by opioid peptides.

Garris, P A · 1990

Endogenous opioid peptides tonically inhibit dopamine release from both pituitary regions.

Trophic effects of enkephalin, beta-endorphine and dynorphine on ventral spinal cord in culture.

Iwasaki, Y · 1990

Enkephalin, beta-endorphin, and dynorphin are not growth factors for ventral spinal cord neurons.

Morphine and opioid peptides selectively inhibit the non-cholinergically mediated neurogenic contraction of guinea-pig isolated bronchial muscle.

Kamikawa, Y · 1990

Opioid peptides selectively inhibit non-cholinergic excitatory neurotransmission in airways via prejunctional receptors, with dynorphin being the most potent endogenous peptide..

Changes in the processing of pro-dynorphin end products in the substantia nigra during neonatal development.

Sei, C A · 1990

Prodynorphin processing matures much faster in the substantia nigra (day 7) than the pituitary (day 21).

High density of zinc-containing and dynorphin B- and substance P-immunoreactive terminals in the marginal division of the rat striatum.

Shu, S Y · 1990

The marginal division of the striatum has higher densities of zinc, dynorphin B-immunoreactive terminals, and substance P-immunoreactive terminals compared to the rest of the striatum..

Hemodynamic responses of conscious rats following intrathecal injections of prodynorphin-derived opioids: independence of action of intrathecal arginine vasopressin.

Thornhill, J A · 1990

Spinal dynorphin A raises blood pressure through kappa opioid receptors independently from vasopressin.

The immunostaining for the hypothalamic vasoactive intestinal peptide, but not for beta-endorphin, dynorphin-A or methionine-enkephalin, is affected by the glucocorticoid milieu in the rat: correlation with the prolactin secretion.

Watanobe, H · 1990

Glucocorticoids regulate hypothalamic VIP expression and prolactin secretion but do not affect beta-endorphin, dynorphin A, or met-enkephalin immunostaining in the hypothalamus..

Apocarboxypeptidase B-sepharose: a specific adsorbent for peptides.

Yasuhara, T · 1990

Apocarboxypeptidase B-Sepharose selectively adsorbs opioid peptides with C-terminal basic residues, providing a novel separation tool for peptide processing research..

Regional distribution of opioidergic nerves in human and canine prostates.

Aumüller, G · 1989

Prostatic opioid innervation comes exclusively from proenkephalin-derived peptides.

The posttranslational processing of prodynorphin in the rat anterior pituitary.

Day, R · 1989

The rat anterior pituitary contains at least six distinct high-molecular-weight intermediates of prodynorphin, and similar forms exist in spinal cord and hypothalamus..

Expression and posttranslational processing of preprodynorphin complementary DNA in the mouse anterior pituitary cell line AtT-20.

Devi, L · 1989

AtT-20 pituitary cells contain all the enzymes needed to process prodynorphin correctly, including at rare monobasic cleavage sites.

Detection of Met-enkephalin and Leu-enkephalin in the posterior pituitary of the holostean fish, Amia calva.

Dores, R M · 1989

Holostean fish have enkephalin peptides with a 3:1 met-to-leu ratio and a novel modified met-enkephalin form, but no detectable prodynorphin-derived peptides..

Immunohistochemical evidence for different opioid systems in the rat superior cervical ganglion as revealed by imipramine treatment and receptor blockade.

Folan, J C · 1989

Prodynorphin and proenkephalin peptides in the superior cervical ganglion respond differently to drugs and denervation, confirming they operate as separate systems with different origins..

Specificity of action of human brain alanyl aminopeptidase on Leu-enkephalin and dynorphin-related peptides.

Gibson, A M · 1989

Brain alanyl aminopeptidase's efficiency drops dramatically with opioid peptide chain length.

Age-dependency and regional distribution of enkephalinergic nerves in human prostate.

Jungblut, T · 1989

Proenkephalin-derived peptide nerve fibers in human prostate were concentrated in the dorsolateral stroma and decreased in density with age.

Ultrastructural basis for interactions between central opioids and catecholamines. I. Rostral ventrolateral medulla.

Milner, T A · 1989

42% of enkephalin terminal targets in the blood pressure control region were catecholamine neurons.

Effect of endogenous opioid peptides on TRH release from rat stomach in vitro.

Mitsuma, T · 1989

Three opioid peptides from different families all inhibited TRH release from rat stomach in a dose-dependent manner, reversible by naloxone..

Effects of opioid peptides on thyrotropin-releasing hormone release from the rat caecum in vitro.

Mitsuma, T · 1989

All three families of opioid peptides inhibited TRH release from rat cecum tissue in a dose-dependent, naloxone-reversible manner..

Prodynorphin peptide distribution in the forebrain of the Syrian hamster and rat: a comparative study with antisera against dynorphin A, dynorphin B, and the C-terminus of the prodynorphin precursor molecule.

Neal, C R · 1989

Prodynorphin peptide distribution differs substantially between hamster and rat in reproduction and emotion-related brain regions, and hamsters may process the precursor protein differently..

Release of endogenous opioid peptides displaces [3H]diprenorphine binding in rat hippocampal slices.

Neumaier, J F · 1989

Endogenous opioid peptide release from hippocampal slices was demonstrated by competitive radioligand displacement.

Steady-state levels of pro-dynorphin-related end-products from the brain of the amphibian, Xenopus laevis.

Sei, C A · 1989

Alpha-neoendorphin is the major prodynorphin end product in Xenopus brain.

A novel bovine spinal cord endoprotease with high specificity for dynorphin B.

Silberring, J · 1989

A novel endoprotease with high specificity for dynorphin B (Km = 11 µM) was identified in bovine spinal cord.

Cocaine selectively increases striatonigral dynorphin levels by a dopaminergic mechanism.

Sivam, S P · 1989

Subchronic cocaine selectively increased striatonigral dynorphin through a dopaminergic mechanism requiring both D1 and D2 receptors.

Distribution of dynorphin B and methionine-enkephalin in the mouse hippocampus: influence of genotype.

van Daal, J H · 1989

Dynorphin B mossy fiber terminal fields in the hippocampus vary by mouse genotype, with C57BL/6 mice having larger intra- and infrapyramidal projections than DBA/2 mice..

Enterochromaffin (EC-) cells of the mammalian gastro-entero-pancreatic (GEP) endocrine system: cellular source of pro-dynorphin-derived peptides.

Cetin, Y · 1988

Enterochromaffin (EC) cells are the most abundant hormone-producing cells in the gut.

Concomitant changes in the in vitro and in vivo release of opioid peptides and luteinizing hormone-releasing hormone from the hypothalamus following blockade of receptors for corticotropin-releasing factor.

Nikolarakis, K E · 1988

Alpha-helical CRF9-41 (a CRF receptor blocker) applied to hypothalamic slices in vitro caused beta-endorphin and met-enkephalin to drop significantly within 10 minutes.

Pre- and postsynaptic actions of GABA on the release of hypothalamic gonadotropin-releasing hormone (GnRH).

Nikolarakis, K E · 1988

GABA at concentrations from 10^-8 to 10^-4 M caused a dose-dependent increase in GnRH release from rat hypothalamic slices.

Central nervous system neuropeptides after peripheral nerve deafferentation.

Panerai, A E · 1988

Regardless of which nerve was cut (right or left sciatic, both sciatic, right brachial plexus, saphenous, or sural), the same brain-wide pattern emerged. Beta-endorphin decreased significantly in all brain areas except the striatum.

Enkephalins interact with substance P-induced aversive behaviour in mice.

Sakurada, T · 1988

Intrathecal (spinal cord) met-enkephalin at low doses markedly reduced the aversive behavior caused by intrathecal substance P.

Distribution of opioid peptides in the preoptic region: immunohistochemical evidence for a steroid-sensitive enkephalin sexual dimorphism.

Simerly, R B · 1988

Three opioid peptide families showed distinct, non-overlapping distributions in the preoptic brain region. Beta-endorphin fibers were mainly in the periventricular nucleus.

Immunohistochemistry of biogenic polypeptides in nerve cells and fibres of the guinea pig inferior mesenteric ganglion after perturbations.

Webber, R H · 1988

Local neurons within the ganglion contribute more peptide-containing nerve fibers than researchers previously believed.

Kainic acid as a tool to study the regulation and function of opioid peptides in the hippocampus.

Hong, J S · 1987

A single injection of kainic acid (1 microgram) into rat brains caused seizures lasting 3 to 6 hours.

Vasopressin, oxytocin, dynorphin, enkephalin and corticotrophin-releasing factor mRNA stimulation in the rat.

Lightman, S L · 1987

Rats drinking 2% salt solution showed progressive increases in three neuropeptide mRNAs in the hypothalamus (a brain region controlling hormones): Vasopressin, oxytocin, and dynorphin mRNAs all increased in the magnocellular neurons of the supraoptic and paraventricular nuclei.

Evidence that thymosins and other biologic response modifiers can function as neuroactive immunotransmitters.

Hall, N R · 1985

The paper argued that certain molecules made by immune cells can send signals directly to the brain.

Anglerfish preprosomatostatin II is processed to somatostatin-28 and contains hydroxylysine at residue 23.

Andrews, P C · 1984

Two versions of somatostatin-28 were isolated from anglerfish tissue.

Identification of a G Protein-Coupled Receptor for Buccalin-Type Peptides in the Mollusk Aplysia: Evolutionary Insights into Neuropeptide Signaling.

Xu, Ju-Ping · 2025

Researchers identified the first buccalin receptor in the sea slug Aplysia californica, designated apBuc/AstA-R.

Research priorities for randomised controlled trials in chronic migraine preventive medication: A stakeholder consensus workshop.

Rees, Sophie · 2024

Using nominal group technique (a structured consensus method), the stakeholders identified their research priorities: 1.

Effects of Kisspeptin Administration in Women With Hypoactive Sexual Desire Disorder: A Randomized Clinical Trial.

Mills, Edouard G · 2022

Kisspeptin administration significantly modulated sexual brain processing in women with HSDD — the first time this has been demonstrated in a clinical population.

Artificial Intelligence Identified Resilient and Vulnerable Female Rats After Traumatic Stress and Ethanol Exposure: Investigation of Neuropeptide Y Pathway Regulation.

Denny, Ray R · 2021

Resilient female rats had higher Y2R mRNA expression in the central amygdala and higher NPY protein levels in the BNST compared to vulnerable and control rats after traumatic stress exposure..

Substance P containing peptide gene delivery vectors for specifically transfecting glioma cells mediated by a neurokinin-1 receptor.

Ding, Guihua · 2021

Peptide vector P-02 (SP-PEG4-K(C18)-(LLHH)3-R9) achieved 36% higher transfection in glioma U87 cells versus normal 293T cells, with NK1 receptor-mediated targeting confirmed.

Substance P and Neurokinin 1 Receptor in Chronic Inflammation and Cancer of the Head and Neck: A Review of the Literature.

Esteban, Francisco · 2021

Substance P and NK1R upregulate cell proliferation, cell migration, and chronic inflammation in head and neck cancers, playing a role in the transition from chronic mucosal inflammation to neoplastic transformation and progression..

Harnessing the Anti-Nociceptive Potential of NK2 and NK3 Ligands in the Design of New Multifunctional μ/δ-Opioid Agonist-Neurokinin Antagonist Peptidomimetics.

Gadais, Charlène · 2021

Three hybrid compounds (SBL-OPNK-5, -7, -9) bearing the KGOP01 scaffold achieved nanomolar μ-opioid receptor affinity, slightly reduced δ-opioid receptor affinity, and (sub)nanomolar NK2 and NK3 binding — the first designed multi-ligands targeting these receptor combinations..

Amylin Analog Pramlintide Induces Migraine-like Attacks in Patients.

Ghanizada, Hashmat · 2021

Pramlintide induced headache in 88% and migraine-like attacks in 41% of patients (vs CGRP: 97% and 56%, differences not significant).

The impact of CGRPergic monoclonal antibodies on prophylactic antimigraine therapy and potential adverse events.

González-Hernández, Abimael · 2021

Anti-CGRP monoclonal antibodies represent a paradigm shift in migraine prevention as the first treatments designed specifically for migraine.

Calcitonin Gene-Related Peptide Monoclonal Antibody Use for the Preventive Treatment of Refractory Headache Disorders in Adolescents.

Greene, Kaitlin A · 2021

In 112 adolescents, CGRP mAbs reduced headache frequency by 2.0 days/month (95% CI -0.8 to -3.2).

UVR-B-induced NKR-1 Expression in Ocular Tissues is blocked by Substance P Receptor Antagonist Fosaprepitant in the Exposed as well as Unexposed Partner Eye.

Gross, Janine · 2021

Fosaprepitant (NK-1R antagonist) blocked UVR-B-induced NKR-1 expression and pro-inflammatory cytokine/chemokine production in both exposed and unexposed partner eyes in a mouse cataract model..

Increased expression of transient receptor potential channels and neurogenic factors associates with cough severity in a guinea pig model.

Guan, Mengyue · 2021

Bleomycin-induced pulmonary fibrosis in guinea pigs caused significantly increased expression of substance P, NK1R, CGRP, TRPA1, and TRPV1 in cough reflex pathways, all positively correlated with enhanced cough sensitivity to capsaicin challenge..

Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development.

Koob, George F · 2021

Multiple neuropeptide systems (CRF, dynorphin, substance P, nociceptin, orexin, vasopressin, NPY, endocannabinoids, and others) are dysregulated in the extended amygdala/habenula during drug withdrawal, driving hyperkatifeia that motivates compulsive drug seeking across substances..

Influence of acupuncture on the expression of VIP, SP, NKA and NKB, cAMP/cGMP and HE content and treatment of bronchial asthma in rats.

Chen, Yujuan · 2020

In a rat model of bronchial asthma, acupuncture altered the levels of several neuropeptides in lung tissue.

Natriuretic peptides and neprilysin inhibition in hypertension and hypertensive organ damage.

Kato, Johji · 2020

ANP and BNP are released by the heart in response to increased pressure or volume.

The Role of Substance P in the Regulation of Bone and Cartilage Metabolic Activity.

Li, Fu-Xing-Zi · 2020

Substance P regulates bone and cartilage metabolism through autocrine/paracrine signaling, promoting cell proliferation, differentiation, matrix synthesis, and fracture healing..

Evaluation of serum level of substance P and tissue distribution of NK-1 receptor in colorectal cancer.

Lorestani, Shima · 2020

Serum substance P was significantly elevated in CRC patients (P=0.001) and tumor tissues overexpressed NK-1R compared to adjacent normal tissue (P=0.01)..

Modulation of Sensory Nerve Function by Insulin: Possible Relevance to Pain, Inflammation and Axon Growth.

Lázár, Bence András · 2020

Insulin receptors are expressed on a specific subset of sensory neurons in both the central and peripheral nervous system.

Antiproliferative effects of [D-Pro2, D-Trp7,9]-Substance P and aprepitant on several cancer cell lines and their selectivity in comparison to normal cells.

Matalińska, Joanna · 2020

Aprepitant potently reduced cancer cell proliferation but was not selective (equally toxic to normal cells); the peptide NK-1 antagonist showed minimal anticancer activity even at 100 µM..

Contribution of NPY Y5 Receptors to the Reversible Structural Remodeling of Basolateral Amygdala Dendrites in Male Rats Associated with NPY-Mediated Stress Resilience.

Michaelson, Sheldon D · 2020

NPY acts through Y5 receptors to cause dendritic hypotrophy in amygdala neurons, reducing excitability and anxiety behavior, while reversing CRF-induced structural hypertrophy — a mechanism for stress resilience..

Neurokinin-1 Receptor Signaling Is Required for Efficient Ca2+ Flux in T-Cell-Receptor-Activated T Cells.

Morelli, Adrian E · 2020

NK1R and its neuropeptide agonists (substance P, hemokinin-1) localize at the immune synapse and are required for efficient calcium flux, activated T cell survival, and Th1/Th17 pro-inflammatory bias..

Neurokinin receptor antagonism: a patent review (2014-present).

Muñoz, Miguel · 2020

Only 5 NK-1R antagonists are clinically approved (all for emesis) despite the tachykinin system's involvement in cancer, pain, itch, obesity, and numerous other conditions — representing significant therapeutic underexploration..

Ghrelin-Mediated Hippocampal Neurogenesis: Implications for Health and Disease.

Buntwal, Luke · 2019

Ghrelin, the hunger hormone released by the stomach during food restriction, promotes the growth of new neurons in the hippocampus — the brain's memory center.

A historical perspective on the role of sensory nerves in neurogenic inflammation.

Sousa-Valente, João · 2018

This historical review traces more than a century of research on how sensory nerves drive inflammation — a process called neurogenic inflammation.

Emerging Roles of Kisspeptin in Sexual and Emotional Brain Processing.

Comninos, Alexander N · 2017

Review consolidating evidence that kisspeptin enhances limbic brain activity to sexual stimuli, reduces negative mood, and modulates brain responses to attraction cues, expanding its role beyond reproductive axis regulation..

VPAC2 (vasoactive intestinal peptide receptor type 2) receptor deficient mice develop exacerbated experimental autoimmune encephalomyelitis with increased Th1/Th17 and reduced Th2/Treg responses.

Tan, Yossan-Var · 2015

Mice lacking the VPAC2 receptor (which responds to the neuropeptides VIP and PACAP) developed much more severe autoimmune brain inflammation (EAE, the animal model for multiple sclerosis).

Central orexin sensitivity, physical activity, and obesity in diet-induced obese and diet-resistant rats.

Novak, Colleen M · 2006

Rats prone to diet-induced obesity (DIO rats) showed significantly decreased spontaneous physical activity after 29 days on a high-fat diet, while diet-resistant (DR) rats maintained their activity levels.

Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior.

Sakurai, T · 1998

This landmark study identified two entirely new neuropeptides — orexin-A and orexin-B — both produced from the same precursor protein in the hypothalamus.