Peptide Opioid Peptides Research

Endorphins, enkephalins, dynorphins, pain modulation

363 peer-reviewed studies

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RPEP-07160StrongReview

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.

RPEP-00739StrongReview

Exploring the opioid system by gene knockout.

Kieffer, Brigitte L · 2002

Opioid gene knockouts reveal distinct, non-redundant roles: enkephalins in analgesia and reward, beta-endorphin in stress analgesia and respiratory control, dynorphins in pain and emotional regulation — each family has a specific functional niche..

RPEP-00626StrongReview

From opiate pharmacology to opioid peptide physiology.

Terenius, L · 2000

The pharmacological uniqueness of opiates implied endogenous opioid ligands must exist, leading to the discovery of enkephalins, beta-endorphin, and dynorphins — a family of peptides with diverse roles in pain, mood, and behavior..

RPEP-00442Strongin-vitro

A potent and selective endogenous agonist for the mu-opiate receptor.

Zadina, J E · 1997

Two novel tetrapeptides, endomorphin-1 (Tyr-Pro-Trp-Phe-NH2) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH2), were identified as potent and selective endogenous agonists of the mu-opioid receptor..

RPEP-00324StrongRCT

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..

RPEP-00351Strongin-vitro

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..

RPEP-00305Strongin-vitro

Pharmacological characterization of the cloned kappa-, delta-, and mu-opioid receptors.

Raynor, K · 1994

Cloned kappa, delta, and mu opioid receptors showed distinct pharmacological profiles matching decades of predictions from classical pharmacology studies..

RPEP-00307StrongAnimal Study

Interleukin 1 beta and corticotropin-releasing factor inhibit pain by releasing opioids from immune cells in inflamed tissue.

Schäfer, M · 1994

IL-1 beta and CRF caused immune cells in inflamed tissue to release opioid peptides that produced local pain relief, blocked by naloxone and anti-opioid antibodies..

RPEP-00280StrongCross-Sectional

Local analgesic effect of endogenous opioid peptides.

Stein, C · 1993

All three opioid peptides found in synovial immune cells.

RPEP-13160Moderatenarrative-review

Effect of kisspeptin, neurokinin, and dynorphin neurons on regulation of reproduction.

Racková, Jana · 2025

KNDy neurons integrate hormonal feedback (estrogen, progesterone, testosterone) and environmental cues to control GnRH pulse frequency and amplitude, making them central regulators of reproductive function..

RPEP-06923Moderateobservational-human-tissue

Nociceptin/Orphanin FQ Opioid Peptide-Receptor Expression in the Endometriosis-Associated Nerve Fibers-Possible Treatment Option?

Guan, Qihui · 2023

NOP receptor expression was detected on peritoneal nerve fibers in both endometriosis patients and healthy controls, but expression was increased in endometriosis-associated nerve fibers.

RPEP-05523Moderateanimal

Interleukin-4 Induces the Release of Opioid Peptides from M1 Macrophages in Pathological Pain.

Labuz, Dominika · 2021

IL-4 via IL-4Rα triggered dose-dependent release of Met-enkephalin, β-endorphin, and dynorphin A from M1 macrophages at injured nerves.

RPEP-05029ModerateReview

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..

RPEP-01314ModerateAnimal Study

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..

RPEP-01378ModerateReview

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..

RPEP-01216ModerateAnimal Study

Potent mitochondria-targeted peptides reduce myocardial infarction in rats.

Cho, Janghyun · 2007

Mitochondria-targeted peptides (SS-31 and analogs) reduced myocardial infarct size by up to 60% in rat ischemia-reperfusion, with efficacy when given before ischemia or at reperfusion — demonstrating potent cardioprotection through preservation of mitochondrial function..

RPEP-01230ModerateAnimal Study

Essential role of mu opioid receptor in the regulation of delta opioid receptor-mediated antihyperalgesia.

Gendron, L · 2007

Mu-opioid receptor function was essential for delta-opioid receptor-mediated anti-hyperalgesia in inflammatory pain, with mu blockade eliminating delta agonist efficacy — demonstrating mu-delta functional dependence and implications for selective opioid drug design..

RPEP-01266ModerateReview

Targeting of opioid-producing leukocytes for pain control.

Machelska, Halina · 2007

Peripheral opioid analgesia from immune cell-derived peptides can be enhanced by: recruiting more opioid-producing leukocytes, increasing per-cell opioid release, or applying peripherally-restricted opioid agonists — achieving pain control without CNS side effects..

RPEP-01295ModerateAnimal Study

Mitochondrial targeting with antioxidant peptide SS-31 prevents mitochondrial depolarization, reduces islet cell apoptosis, increases islet cell yield, and improves posttransplantation function.

Thomas, Dolca A · 2007

SS-31 (mitochondria-targeted peptide) prevented mitochondrial depolarization and apoptosis in pancreatic islet cells, preserved glucose-stimulated insulin secretion, and improved glycemic control in diabetic animals — protecting the beta-cells that diabetes progressively destroys..

RPEP-01145ModerateAnimal Study

Differential involvement of endogenous opioids in sucrose consumption and food reinforcement.

Hayward, Michael D · 2006

Kappa-opioid (dynorphin) and mu-opioid (endorphin/enkephalin) systems differentially regulated sucrose preference versus food-reinforced operant behavior in mice — different opioid families mediate different components of food reward and palatable eating..

RPEP-01032ModerateReview

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..

RPEP-01046ModerateReview

The endogenous opioid system and clinical pain management.

Holden, Janean E · 2005

The endogenous opioid system (endorphins, enkephalins, dynorphins) provides the biological foundation for clinical pain management: understanding endogenous analgesia mechanisms improves opioid drug selection, dosing, and integration with non-pharmacological approaches..

RPEP-01054ModerateReview

Endogenous opioid analgesia in peripheral tissues and the clinical implications for pain control.

Kapitzke, Daniel · 2005

Peripheral endogenous opioid analgesia from immune cell-released peptides at inflammation sites provides clinically significant pain control through peripheral opioid receptors, exploitable with intra-articular, topical, and peripherally-restricted opioid drugs without CNS side effects..

RPEP-01075ModerateReview

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..

RPEP-00922ModerateReview

Acupuncture and endorphins.

Han, Ji-Sheng · 2004

Acupuncture and electroacupuncture produce analgesia through frequency-specific release of endogenous opioid peptides: low frequency releases endorphins/enkephalins (mu/delta) and high frequency releases dynorphins (kappa), confirmed across animal and human studies..

RPEP-00953ModerateReview

Conformational analysis of opioid peptides in the solid states and the membrane environments by NMR spectroscopy.

Naito, Aira · 2004

Opioid peptide conformations in membrane-mimetic environments differed significantly from solution structures, revealing the biologically relevant receptor-interacting conformations for structure-based opioid drug design..

RPEP-00957ModerateReview

Cross-talk of opioid peptide receptor and beta-adrenergic receptor signalling in the heart.

Pepe, Salvatore · 2004

Cardiac opioid peptide receptors (delta, kappa) and beta-adrenergic receptors share G-protein signaling pathways, creating functional cross-talk that modulates contractility, arrhythmia susceptibility, and ischemic preconditioning cardioprotection..

RPEP-00994ModerateReview

Non-opioid actions of opioid peptides.

Wollemann, Mária · 2004

Endogenous opioid peptides have extensive non-opioid receptor activities: immune modulation, cell proliferation control (via OGFr), cardiovascular protection, neuroprotection, and antimicrobial effects — mediated through non-classical receptors and direct physicochemical mechanisms..

RPEP-00822Moderateclinical-trial

Casein and whey exert different effects on plasma amino acid profiles, gastrointestinal hormone secretion and appetite.

Hall, W L · 2003

Whey protein produced greater short-term satiety than casein in humans, with faster amino acid absorption, higher plasma amino acid peaks, and different gastrointestinal hormone (CCK, GLP-1) profiles..

RPEP-00846ModerateAnimal Study

Different mechanisms of intrinsic pain inhibition in early and late inflammation.

Machelska, Halina · 2003

Early inflammatory pain inhibition was mediated by CRF-triggered opioid release from immune cells, while late inflammation used chemokine (CXCL1/2)-stimulated opioid release — the intrinsic pain control mechanism evolves with inflammation maturation..

RPEP-00859Moderatein-vitro

Peptidases prevent mu-opioid receptor internalization in dorsal horn neurons by endogenously released opioids.

Song, Bingbing · 2003

Multiple peptidase inhibition in rat spinal cord slices allowed endogenous opioid peptides to accumulate and trigger mu-opioid receptor internalization, revealing that rapid enzymatic degradation normally prevents full endogenous opioid receptor activation..

RPEP-00728Moderateclinical-trial

beta-Endorphin modulation of pressor response to hyperventilation in hypertensive patients.

Fontana, Fiorella · 2002

Beta-endorphin levels predicted blood pressure response to hyperventilation in hypertensives: high endorphin = BP decrease; low endorphin with high norepinephrine/dynorphin = BP increase — opioids modulate cardiovascular stress response..

RPEP-00754ModerateReview

Endomorphins and related opioid peptides.

Okada, Yoshio · 2002

Endomorphins 1 and 2 are the most mu-opioid selective endogenous peptides, with potent analgesia and distinct pharmacological profiles suggesting separate roles in pain modulation and unique therapeutic potential..

RPEP-00759ModerateAnimal Study

Dietary peptides induce satiety via cholecystokinin-A and peripheral opioid receptors in rats.

Pupovac, Jelena · 2002

Dietary peptides from protein digestion induced satiety through both CCK-A and peripheral opioid receptor pathways, with the relative contribution of each pathway varying by protein source — different foods activate different satiety signals..

RPEP-00648Moderatein-vitro

A single nucleotide polymorphic mutation in the human mu-opioid receptor severely impairs receptor signaling.

Befort, K · 2001

The N40D polymorphism in the human mu-opioid receptor severely impaired beta-endorphin-stimulated G-protein coupling and downstream signaling, potentially explaining ~10% of the population's altered pain sensitivity and opioid drug response..

RPEP-00653ModerateAnimal Study

Methionine-enkephalin-and Dynorphin A-release from immune cells and control of inflammatory pain.

Cabot, Peter J · 2001

Immune cells at sites of inflammation contain and release met-enkephalin, dynorphin A, and beta-endorphin, which activate peripheral opioid receptors on sensory nerves to provide local inflammatory pain control..

RPEP-00663ModerateCross-Sectional

Opioid peptides attenuate blood pressure increase in acute respiratory failure.

Fontana, F · 2001

Elevated plasma beta-endorphin and met-enkephalin in COPD patients with acute respiratory failure inversely correlated with blood pressure, demonstrating endogenous opioid-mediated attenuation of the hypertensive stress response..

RPEP-00693ModerateReview

Opioids in chronic pain.

Przewłocki, R · 2001

Endogenous opioid peptides operate through distinct mu, delta, kappa, and NOP receptor systems with unique distribution and function in chronic pain conditions, offering multiple targets for developing targeted, safer analgesics..

RPEP-00708Moderateclinical-trial

The inhibitory effect of Selank on enkephalin-degrading enzymes as a possible mechanism of its anxiolytic activity.

Zozulya, A A · 2001

Anxiety patients showed accelerated enkephalin degradation, and Selank's anxiolytic effect correlated with inhibition of enkephalin-degrading enzymes, preserving endogenous opioid-mediated anxiety relief..

RPEP-00577ModerateReview

Cardiac opioids.

Barron, B A · 2000

The heart produces and locally utilizes enkephalins, dynorphins, and endorphins as autocrine/paracrine cardioprotective factors, potentially mediating ischemic preconditioning..

RPEP-00618ModerateReview

Effects of milk-derived bioactives: an overview.

Shah, N P · 2000

Milk-derived peptides from casein and whey digestion include opioid peptides (casomorphins), antihypertensive peptides (casokinins), mineral carriers (casein phosphopeptides), and other bioactives with diverse health effects..

RPEP-00517ModerateReview

Role of opioid ligands in the irritable bowel syndrome.

Corazziari, E · 1999

Endogenous opioid peptides regulate visceral pain sensitivity, gastrointestinal motility, and secretion through mu, delta, and kappa receptors in the brain, spinal cord, and enteric nervous system, with dysfunction potentially underlying IBS symptoms..

RPEP-00459Moderateclinical-trial

Endogenous opioid peptides and mental stress in congestive heart failure patients.

Fontana, F · 1998

NYHA class III heart failure patients had elevated resting beta-endorphin and neurohormone levels, with naloxone-modifiable stress responses, confirming active opioid system involvement in cardiovascular stress regulation..

RPEP-00460Moderateclinical-trial

Opioid peptides in response to mental stress in asymptomatic dilated cardiomyopathy.

Fontana, F · 1998

Asymptomatic dilated cardiomyopathy patients had normal resting opioid peptide levels but showed altered opioid peptide responses to mental stress, alongside elevated ANF levels..

RPEP-00499ModerateReview

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..

RPEP-00407Moderateclinical-trial

Opioid peptide modulation of circulatory and endocrine response to mental stress in humans.

Fontana, F · 1997

Low blood pressure responders to mental stress had significantly higher beta-endorphin release than high responders, suggesting endogenous opioids buffer the cardiovascular stress response..

RPEP-00408Moderateclinical-trial

Pressor effects of endogenous opioid system during acute episodes of blood pressure increases in hypertensive patients.

Fontana, F · 1997

Beta-endorphin, met-enkephalin, and dynorphin B levels changed significantly during acute blood pressure increases in hypertensive patients, alongside ANF and endothelin-1 alterations..

RPEP-00410ModerateReview

Endogenous opioid systems and alcohol addiction.

Herz, A · 1997

Mu and delta opioid receptors mediate alcohol's rewarding properties while kappa receptors oppose them, with all three endogenous opioid peptide families playing distinct roles in addiction..

RPEP-00355ModerateReview

Opiate receptor-mediated mechanisms in the regulation of cerebral blood flow.

Benyó, Z · 1996

Endogenous opioid peptides in cerebral perivascular nerves and CSF actively regulate cerebral blood flow through opiate receptors, with concentrations changing in response to perfusion pressure and oxygen tension..

RPEP-00366ModerateAnimal Study

Activation of mu-opioid receptors are required for the conditioned enhancement of NK cell activity.

Hsueh, C M · 1996

Conditioned enhancement of NK cell activity depends on mu-opioid receptor activation, with beta-endorphin and met-enkephalin as the key mediating peptides..

RPEP-00367ModerateAnimal Study

Chronic intracerebroventricular administration of beta-endorphin augments natural killer cell cytotoxicity in rats.

Jonsdottir, I H · 1996

Chronic intracerebroventricular beta-endorphin infusion significantly enhanced in vivo NK cell cytotoxicity and altered splenic and peripheral blood lymphocyte phenotypes..

RPEP-00374Moderatein-vitro

Opioid receptor agonists activate pertussis toxin-sensitive G proteins and inhibit adenylyl cyclase in canine cardiac sarcolemma.

Niroomand, F · 1996

Mu, delta, and kappa opioid receptors in cardiac sarcolemma activate pertussis toxin-sensitive G proteins and inhibit adenylyl cyclase, confirming a complete opioid signaling pathway in the heart..

RPEP-00385ModerateReview

Endogenous opioid regulation of hippocampal function.

Simmons, M L · 1996

Proenkephalin-derived peptides increase hippocampal excitability via mu/delta receptors, while prodynorphin-derived peptides decrease it via kappa receptors, providing opposing regulation of memory circuits..

RPEP-00388ModerateAnimal Study

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..

RPEP-00389ModerateAnimal Study

Inhibition of dynorphin-converting enzymes prolongs the antinociceptive effect of intrathecally administered dynorphin in the mouse formalin test.

Tan-No, K · 1996

Peptidase inhibitors significantly prolonged the antinociceptive effect of intrathecally administered dynorphin A (0.5-2 nmol) and dynorphin B (2-8 nmol) in the formalin test..

RPEP-00394ModerateAnimal Study

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..

RPEP-00317ModerateReview

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..

RPEP-00320ModerateAnimal Study

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..

RPEP-00332ModerateReview

A role for hippocampal opioids in long-term functional plasticity.

Morris, B J · 1995

Hippocampal dynorphins and enkephalins regulate synaptic transmission efficiency at granule cell synapses, with opioid levels changing dramatically under different physiological and pathological conditions..

RPEP-00337ModerateAnimal Study

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..

RPEP-00342Moderatein-vitro

Specific N- or C-terminus modified dynorphin and beta-endorphin peptides can selectively block excitatory opioid receptor functions in sensory neurons and unmask potent inhibitory effects of opioid agonists.

Shen, K F · 1995

N- or C-terminus modified dynorphin and beta-endorphin selectively blocked excitatory opioid receptor functions, dramatically enhancing the pain-relieving effects of opioid agonists..

RPEP-00345ModerateAnimal Study

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..

RPEP-00349ModerateAnimal Study

Brain and plasma levels of opioid peptides are altered in rats with thioacetamide-induced fulminant hepatic failure: implications for the treatment of hepatic encephalopathy with opioid antagonists.

Yurdaydin, C · 1995

Fulminant hepatic failure significantly altered Met-enkephalin, Leu-enkephalin, dynorphin A, and beta-endorphin levels in multiple brain regions and plasma..

RPEP-00285ModerateRCT

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..

RPEP-00299ModerateAnimal Study

Effects of a mixture of peptidase inhibitors (amastatin, captopril and phosphoramidon) on Met-enkephalin-, beta-endorphin-, dynorphin-(1-13)- and electroacupuncture-induced antinociception in rats.

Kishioka, S · 1994

Peptidase inhibitor mixture enhanced antinociception from met-enkephalin, beta-endorphin, and electroacupuncture, but not dynorphin-(1-13)..

RPEP-00300ModerateCross-Sectional

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..

RPEP-00301ModerateCross-Sectional

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..

RPEP-00308ModerateReview

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..

RPEP-00256ModerateReview

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..

RPEP-00258ModerateCross-Sectional

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.

RPEP-00261ModerateAnimal Study

Endogenous opioid regulation of oxytocin secretion through pregnancy in the rat.

Douglas, A J · 1993

Naloxone significantly increased plasma oxytocin on days 15, 18, and 21 of pregnancy but not in non-pregnant, early pregnant, or post-partum rats..

RPEP-00263ModerateCross-Sectional

Relationship between plasma atrial natriuretic factor and opioid peptide levels in healthy subjects and in patients with acute congestive heart failure.

Fontana, F · 1993

ANF, beta-endorphin, met-enkephalin, dynorphin, and noradrenaline were all elevated in acute CHF.

RPEP-00265ModerateCross-Sectional

Decreased cerebrospinal fluid beta-endorphin and increased pain sensitivity in patients with functional abdominal pain.

Jørgensen, L S · 1993

CSF beta-endorphin was significantly decreased in functional abdominal pain patients.

RPEP-00267ModerateReview

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..

RPEP-00268Moderatein-vitro

A single residue, aspartic acid 95, in the delta opioid receptor specifies selective high affinity agonist binding.

Kong, H · 1993

Asp95Asn mutation in delta opioid receptor eliminated selective high-affinity agonist binding while preserving antagonist binding.

RPEP-00276ModerateCross-Sectional

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

Samuelsson, H · 1993

Cancer pain patients had altered CSF neuropeptide profiles.

RPEP-00220ModerateReview

Properties and functions of human placental opioid system.

Ahmed, M S · 1992

Human placenta contains exclusively kappa opioid receptors (MW ~63,000).

RPEP-00223ModerateCross-Sectional

Plasma endogenous opioid levels in acute myocardial infarction patients, with and without pain.

Bernardi, P · 1992

Transient plasma beta-endorphin elevation in painful AMI (Group II, n=16) that normalized when pain ceased.

RPEP-00244ModerateReview

Opioid peptide drug development: transport of opioid chimeric peptides through the blood-brain barrier.

Pardridge, W M · 1992

Chimeric peptides coupling opioid peptides to BBB transport vectors allow brain delivery of enkephalin and dynorphin analogs in vivo.

RPEP-00246ModerateAnimal Study

Gene expression and localization of opioid peptides in immune cells of inflamed tissue: functional role in antinociception.

Przewłocki, R · 1992

All three opioid precursor mRNAs detected in inflamed tissue.

RPEP-00202ModerateReview

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..

RPEP-00213ModerateReview

Opiate tolerance and dependence: recent findings and synthesis.

Trujillo, K A · 1991

Opiate tolerance involves multiple mechanisms: environmental learning, NMDA receptor involvement, second messenger system adaptations, and altered intracellular signaling.

RPEP-00215ModerateCross-Sectional

No evidence for endorphin deficiency in fibromyalgia following investigation of cerebrospinal fluid (CSF) dynorphin A and Met-enkephalin-Arg6-Phe7.

Vaerøy, Henning · 1991

CSF dynorphin A (14.3 fmol/ml) and met-enkephalin-Arg-Phe (35.1 fmol/ml) were normal in fibromyalgia.

RPEP-00147Moderatein-vitro

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.

RPEP-00158Moderatein-vitro

Enkephalins modulate inhibitory neuromuscular transmission in circular muscle of human colon via delta-opioid receptors.

Hoyle, C H · 1990

Enkephalins inhibit non-adrenergic, non-cholinergic inhibitory neurotransmission in human colon through prejunctional delta-opioid receptors with high selectivity..

RPEP-00162ModerateAnimal Study

The occurrence and receptor specificity of endogenous opioid peptides within the pancreas and liver of the rat. Comparison with brain.

Khawaja, X Z · 1990

Pancreas and liver contain substantial opioid peptide levels exceeding brain content, with functional delta and kappa receptors on pancreatic islets.

RPEP-00164Moderatein-vitro

Opioid and nicotine receptors affect growth regulation of human lung cancer cell lines.

Maneckjee, R · 1990

Lung cancer cells have an opioid-based growth suppression system that nicotine can override.

RPEP-00170ModerateAnimal Study

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.

RPEP-00171ModerateAnimal Study

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.

RPEP-00172ModerateAnimal Study

Opioids from immunocytes interact with receptors on sensory nerves to inhibit nociception in inflammation.

Stein, C · 1990

Immune cells in inflamed tissue release opioid peptides that activate receptors on sensory nerve terminals, producing local pain relief.

RPEP-00175ModerateAnimal Study

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..

RPEP-00177Moderatein-vitro

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.

RPEP-00110ModerateReview

The neurobiology of pain and its modulation.

Dubner, R · 1989

Pain modulation involves three opioid peptide families plus serotonin and norepinephrine.

RPEP-00134Moderatein-vitro

Lack of effect of opioid peptides, morphine and naloxone on superoxide formation in human neutrophils and HL-60 leukemic cells.

Seifert, R · 1989

No opioid peptide or morphine, across a wide concentration range, affected superoxide formation in human neutrophils or HL-60 cells under defined experimental conditions..

RPEP-00143ModerateAnimal Study

Induction of the gene encoding pro-dynorphin by experimentally induced arthritis enhances staining for dynorphin in the spinal cord of rats.

Weihe, E · 1989

Chronic arthritis activates the prodynorphin gene in spinal cord neurons, increasing both mRNA and peptide levels.

RPEP-00064ModerateAnimal Study

Levels of endogenous opioids and effects of an opiate antagonist during regional cerebral ischemia in rats.

Andrews, B T · 1988

After middle cerebral artery occlusion (a stroke model) in rats, the opioid antagonist WIN at doses of 0.4 to 400 micrograms/kg produced several benefits. All WIN doses significantly increased mean arterial blood pressure compared to saline controls.

RPEP-00079ModerateReview

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.

RPEP-00081ModerateAnimal Study

Inflammation of the hind limb as a model of unilateral, localized pain: influence on multiple opioid systems in the spinal cord of the rat.

Millan, M J · 1988

Within 24 hours of inflammation, dynorphin increased specifically in the ipsilateral (same-side) dorsal horn of the spinal cord.

RPEP-00040ModerateCross-Sectional

Expression of opioid peptides in tumors.

Bostwick, D G · 1987

Using a "pan-opioid" antibody that detects all opioid peptides, researchers screened 108 tumors.

RPEP-00052ModerateAnimal Study

Endogenous opioids may mediate secondary damage after experimental brain injury.

McIntosh, T K · 1987

Dynorphin A accumulated in injured brain regions after fluid-percussion brain injury in cats.

RPEP-00059ModerateAnimal Study

Peptide opioid antagonist separates peripheral and central opioid antitransit effects.

Shook, J E · 1987

Peripheral mu-opioid receptors in the gut can independently slow gastrointestinal transit.

RPEP-12838Preliminaryin-vitro

Receptor-mediated Gi-3 activation in mammalian and human brain membranes: Reestablishment method and its application to nociceptin/orphanin FQ opioid peptide (NOP) receptor/Gi-3 interaction.

Odagaki, Yuji · 2025

Researchers reestablished a specialized lab assay (GTPγS binding/immunoprecipitation) to measure how the nociceptin/orphanin FQ peptide activates a specific signaling protein called Gαi-3 in brain tissue.

RPEP-01347PreliminaryAnimal Study

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..

RPEP-01358Preliminaryin-vitro

Transport of micro-opioid receptor agonists and antagonist peptides across Caco-2 monolayer.

Iwan, Małgorzata · 2008

Mu-opioid peptide agonists and antagonists showed variable Caco-2 monolayer permeability, with some achieving transcellular transport — assessing oral bioavailability potential and identifying which opioid peptide structures achieve gut barrier crossing..

RPEP-01365PreliminaryAnimal Study

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..

RPEP-01372PreliminaryAnimal Study

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..

RPEP-01416PreliminaryAnimal Study

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..

RPEP-01425Preliminaryin-vitro

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..

RPEP-01429PreliminaryAnimal Study

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..

RPEP-01214PreliminaryAnimal Study

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..

RPEP-01215Preliminaryin-vitro

Dynorphin peptides differentially regulate the human kappa opioid receptor.

Chen, Yong · 2007

Different prodynorphin-derived peptides (dynorphin A, dynorphin B, alpha-neoendorphin) showed differential kappa receptor regulation: distinct patterns of internalization, signaling efficacy, and receptor recycling — demonstrating biased agonism from endogenous ligands..

RPEP-01225PreliminaryAnimal Study

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..

RPEP-01237PreliminaryAnimal Study

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..

RPEP-01249PreliminaryReview

Polymorphism of bovine beta-casein and its potential effect on human health.

Kamiński, Stanisław · 2007

A1 beta-casein releases more beta-casomorphin-7 (BCM-7) during digestion than A2, with BCM-7 showing opioid, immunomodulatory, and GI effects that may explain the health differences attributed to A1 versus A2 milk consumption..

RPEP-01268PreliminaryAnimal Study

Involvement of endogenous opioid peptides in the antinociception induced by the novel dermorphin tetrapeptide analog amidino-TAPA.

Mizoguchi, Hirokazu · 2007

Amidino-TAPA, a novel dermorphin tetrapeptide analog, produced antinociception partly mediated by endogenous opioid peptide release (confirmed by antiserum blocking), extending the drug-endogenous amplification mechanism to a new opioid drug class..

RPEP-01308Preliminaryin-vitro

Opioids and migration, chemotaxis, invasion, and adhesion of human cancer cells.

Zagon, Ian S · 2007

Opioid peptides modulated cancer cell migration, chemotaxis, invasion, and adhesion in a peptide-type and cancer-type dependent manner, suggesting the opioid system influences metastatic behavior — with implications for opioid drug use in cancer patients..

RPEP-01150PreliminaryAnimal Study

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..

RPEP-01163PreliminaryAnimal Study

Naloxone-blocked depriming effect of anxiolytic selank on apomorphine-induced behavioral manifestations of hyperfunction of dopamine system.

Meshavkin, V K · 2006

Naloxone blocked Selank's depriming effect on apomorphine-induced dopaminergic behavioral manifestations, directly confirming opioid system involvement in Selank's anxiolytic mechanism — linking its anti-anxiety action to enkephalin protection..

RPEP-01167PreliminaryAnimal Study

Contribution of spinal mu(1)-opioid receptors and dynorphin B to the antinociception induced by Tyr-d-Arg-Phe-Sar.

Mizoguchi, Hirokazu · 2006

Tyr-d-Arg-Phe-Sar analgesia at the spinal level involved both direct mu-1 opioid receptor activation and endogenous dynorphin B release, with anti-dynorphin antibodies partially blocking the effect — confirming dual direct + endogenous amplification mechanism..

RPEP-01195Preliminaryin-vitro

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..

RPEP-01196PreliminaryAnimal Study

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..

RPEP-01197PreliminaryAnimal Study

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..

RPEP-01019PreliminaryAnimal Study

Morphine-induced changes in the activity of proopiomelanocortin and prodynorphin systems in zymosan-induced peritonitis in mice.

Chadzinska, M · 2005

Morphine modified proopiomelanocortin and prodynorphin system activity in immune cells during zymosan-induced peritonitis, demonstrating that exogenous opioid drugs alter the endogenous opioid-immune pain control system at inflammation sites..

RPEP-01090PreliminaryAnimal Study

Differential mechanisms of antianalgesia induced by endomorphin-1 and endomorphin-2 in the ventral periaqueductal gray of the rat.

Terashvili, Maia · 2005

High-dose endomorphin-1 anti-analgesia in ventral PAG was mediated by direct NMDA receptor activation, while endomorphin-2 worked through dynorphin A release → kappa/NMDA pathways — two endogenous mu-agonists producing pain through distinct mechanisms..

RPEP-01106Preliminaryin-vitro

Opioids and differentiation in human cancer cells.

Zagon, Ian S · 2005

Met-enkephalin (OGF) through the OGFr receptor promoted differentiation of human cancer cells toward more mature phenotypes, reducing proliferative capacity — adding differentiation induction to its known growth-inhibitory anti-cancer mechanism..

RPEP-00884PreliminaryAnimal Study

The effect of CNS opioid on autonomic nervous and cardiovascular responses in diet-induced obese rats.

Barnes, Maria J · 2004

ICV beta-endorphin decreased blood pressure in lean rats but increased it in diet-induced obese rats, with enhanced sympathetic activation and reduced vagal tone — demonstrating a fundamental opioid-cardiovascular control reversal in obesity..

RPEP-00914Preliminaryclinical-trial

Opioid peptide response to spinal cord stimulation in chronic critical limb ischemia.

Fontana, Fiorella · 2004

Spinal cord stimulation in chronic critical limb ischemia patients increased CSF beta-endorphin levels, correlating with improved microvascular flow and wound healing — an endogenous opioid mechanism for SCS therapeutic effects..

RPEP-00926PreliminaryAnimal Study

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..

RPEP-00932Preliminaryin-vitro

The influence of opioid peptides on steroidogenesis in porcine granulosa cells.

Kaminski, T · 2004

Opioid peptides differentially modulated granulosa cell steroidogenesis: inhibiting progesterone while stimulating estradiol through kappa and mu receptor subtypes, revealing a complex opioid regulatory layer in ovarian hormone production..

RPEP-00946PreliminaryAnimal Study

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..

RPEP-00963PreliminaryAnimal Study

Opioid receptors and acetaminophen (paracetamol).

Raffa, Robert B · 2004

Acetaminophen's spinal/supraspinal antinociceptive self-synergy was attenuated by opioid receptor antagonists in mice, demonstrating an opioid receptor component to acetaminophen's pain-relieving mechanism..

RPEP-00968PreliminaryAnimal Study

Relative contribution of endogenous opioids to myocardial ischemic tolerance.

Romano, Matthew A · 2004

Selective opioid receptor and peptide antibody blocking revealed delta-opioid (enkephalin) and kappa-opioid (dynorphin) systems as the primary contributors to myocardial ischemic tolerance, with quantified relative contributions of each endogenous opioid family..

RPEP-00996PreliminaryAnimal Study

Nonopioidergic mechanism mediating morphine-induced antianalgesia in the mouse spinal cord.

Wu, Hsiang-En · 2004

High-dose IT morphine produced anti-analgesia mediated by spinal dynorphin release and NMDA receptor activation (blocked by MK-801 and anti-dynorphin), demonstrating a universal opioid-induced hyperalgesia mechanism across both synthetic and endogenous opioids..

RPEP-00795PreliminaryAnimal Study

Purification and quantification of opioid peptides in bone and joint tissues--a methodological study in the rat.

Bergström, J · 2003

Met-enkephalin-Arg-Phe and dynorphin B were quantified in rat cortical bone, periosteum, bone marrow, joint cartilage, and synovial membrane, establishing a local opioid peptide system in musculoskeletal tissues..

RPEP-00800Preliminaryin-vitro

Activation of delta- and kappa-opioid receptors by opioid peptides protects cardiomyocytes via KATP channels.

Cao, Zhiping · 2003

Delta-opioid (met-enkephalin) and kappa-opioid (dynorphin A) receptor activation protected cardiomyocytes from simulated ischemia through KATP channel opening, confirming the opioid-KATP cardioprotection pathway..

RPEP-00829Preliminaryin-vitro

Identification of a novel Na+- and Cl--coupled transport system for endogenous opioid peptides in retinal pigment epithelium and induction of the transport system by HIV-1 Tat.

Hu, Huankai · 2003

A novel Na+/Cl--coupled opioid peptide transport system was identified in retinal pigment epithelial cells, enabling active regulation of local opioid peptide concentrations at the blood-retinal barrier..

RPEP-00831PreliminaryAnimal Study

Close apposition of dynorphin-positive nerve fibres to lymphocytes in the liver suggests opioidergic neuroimmunomodulation.

Kaiser, Matthias J T · 2003

Dynorphin-positive nerve fibers were found in close apposition to lymphocytes in the rat liver, providing anatomical evidence for direct opioidergic neuroimmunomodulation of hepatic immune responses..

RPEP-00832Preliminaryin-vitro

The regulation of steroidogenesis by opioid peptides in porcine theca cells.

Kaminski, T · 2003

Mu-opioid receptor agonists inhibited basal and LH-stimulated progesterone and androstenedione production in porcine theca cells in a dose-dependent manner, demonstrating direct opioid peptide control of ovarian steroidogenesis..

RPEP-00840Preliminaryin-vitro

Developmental changes in the inhibition of cultured rat uterine cell proliferation by opioid peptides.

Környei, J L · 2003

Opioid peptides directly inhibited uterine cell proliferation in a developmental stage-dependent manner: strongest in immature tissue, diminishing with maturation, with different receptor subtypes active at different stages..

RPEP-00844PreliminaryAnimal Study

State-dependent modulation of feeding behavior by proopiomelanocortin-derived beta-endorphin.

Low, Malcolm J · 2003

POMC-derived beta-endorphin selectively modulated the appetitive (wanting/seeking) phase of feeding behavior in a deprivation-state-dependent manner, separating opioid reward from hunger-driven consumption..

RPEP-00855PreliminaryAnimal Study

Long-term effects of short and long periods of maternal separation on brain opioid peptide levels in male Wistar rats.

Ploj, Karolina · 2003

Both short and long maternal separation produced distinct, persistent alterations in brain opioid peptide levels (dynorphin, met-enkephalin) across reward and stress regions in adult rats, demonstrating lasting neurochemical consequences of early life experience..

RPEP-00863PreliminaryAnimal Study

Endogenous opioid peptides contribute to antinociceptive potency of intrathecal [Dmt1]DALDA.

Szeto, Hazel H · 2003

Intrathecal [Dmt1]DALDA analgesia was partly mediated by endogenous opioid peptide release (confirmed by opioid antiserum blocking), demonstrating drug-induced amplification through the endogenous opioid system..

RPEP-00864PreliminaryAnimal Study

Aggression and the three opioid families (endorphins, enkephalins, and dynorphins) in mice.

Tordjman, Sylvie · 2003

All three endogenous opioid peptide families (endorphins, enkephalins, dynorphins) inversely correlated with aggression across brain regions, with each acting through distinct receptor systems (mu, delta, kappa) and neural circuits..

RPEP-00865PreliminaryAnimal Study

Milk bioactive peptides and beta-casomorphins induce mucus release in rat jejunum.

Trompette, Aurélien · 2003

Beta-casomorphin-7 and casein hydrolysate stimulated mucus release in rat jejunum through mu-opioid receptor activation, providing a direct mechanism for dairy-derived gut protection through opioid peptide signaling..

RPEP-00867Preliminaryin-vitro

Dynorphin B is an agonist of nuclear opioid receptors coupling nuclear protein kinase C activation to the transcription of cardiogenic genes in GTR1 embryonic stem cells.

Ventura, Carlo · 2003

Dynorphin B activated nuclear opioid receptors coupling to nuclear PKC activation, which induced cardiac transcription factors (GATA-4, Nkx-2.5) for cardiogenesis in embryonic stem cells — a novel nuclear signaling mechanism..

RPEP-00868Preliminaryin-vitro

Protein kinase C signaling transduces endorphin-primed cardiogenesis in GTR1 embryonic stem cells.

Ventura, Carlo · 2003

Opioid-primed cardiogenesis in GTR1 embryonic stem cells was mediated by PKC epsilon nuclear translocation, which activated GATA-4 and Nkx-2.5 cardiac transcription — mapping the complete opioid-to-cardiac differentiation signaling cascade..

RPEP-00871PreliminaryAnimal Study

Peripheral opioidergic regulation of the tracheobronchial mucociliary transport system.

Wang, Lian · 2003

Peripheral opioid receptor activation in airway mucosa increased net water absorption, affecting mucociliary transport — identifying an opioidergic regulation of tracheobronchial respiratory defense mechanisms..

RPEP-00874PreliminaryAnimal Study

Dynorphinergic mechanism mediating endomorphin-2-induced antianalgesia in the mouse spinal cord.

Wu, Hsiang-En · 2003

High-dose intrathecal endomorphin-2 produced anti-analgesia through spinal dynorphin release activating NMDA receptors, demonstrating a dose-dependent flip from opioid analgesia to opioid-induced pain generation..

RPEP-00875Preliminaryin-vitro

Opioids and the apoptotic pathway in human cancer cells.

Zagon, Ian S · 2003

Met-enkephalin (OGF) inhibited cancer proliferation through OGFr nuclear translocation and activation of p16/p21 cell cycle inhibitors across pancreatic, colon, and squamous cell cancers — a non-classical opioid anti-cancer mechanism..

RPEP-00747Preliminaryin-vitro

The alpha9/alpha10-containing nicotinic ACh receptor is directly modulated by opioid peptides, endomorphin-1, and dynorphin B, proposed efferent cotransmitters in the inner ear.

Lioudyno, M I · 2002

Endomorphin-1 and dynorphin A directly modulated alpha9/alpha10 nicotinic ACh receptors (not through opioid receptors), providing a molecular mechanism for opioid peptide modulation of auditory and vestibular function..

RPEP-00774PreliminaryAnimal Study

Effects of Selank on behavioral reactions and activities of plasma enkephalin-degrading enzymes in mice with different phenotypes of emotional and stress reactions.

Sokolov, O Yu · 2002

Selank reduced anxiety behavior in naturally anxious BALB/c mice while modifying enkephalin-degrading enzyme activity, with the anxiolytic effect phenotype-dependent — working most in animals with the greatest enkephalin degradation..

RPEP-00775PreliminaryAnimal Study

Alteration in endogenous opioid systems due to chronic inflammatory pain conditions.

Spetea, Mariana · 2002

Chronic arthritic pain produced region-specific alterations in dynorphin B, met-enkephalin, and opioid receptor levels across brain, spinal cord, and pituitary, demonstrating multi-level opioid system adaptation to chronic inflammatory pain..

RPEP-00778PreliminaryAnimal Study

Intrathecally administered big dynorphin, a prodynorphin-derived peptide, produces nociceptive behavior through an N-methyl-D-aspartate receptor mechanism.

Tan-No, Koichi · 2002

Intrathecal big dynorphin at femtomole doses caused nociceptive behavior through NMDA receptor activation (blocked by MK-801) but not through opioid receptors (not blocked by naloxone), with higher doses causing reversible paralysis..

RPEP-00784PreliminaryAnimal Study

Roles of endogenous opioid peptides in modulation of nocifensive response to formalin.

Wu, Hsiang-En · 2002

Phase- and level-specific pain modulation: beta-endorphin supraspinal/early phase; enkephalins spinal/late phase; dynorphin both levels/both phases — the most detailed mapping of endogenous opioid pain control organization..

RPEP-00649PreliminaryAnimal Study

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..

RPEP-00673PreliminaryAnimal Study

Rostral ventrolateral medullary opioid receptor subtypes in the inhibitory effect of electroacupuncture on reflex autonomic response in cats.

Li, P · 2001

Electroacupuncture inhibited cardiovascular pressor reflexes through mu and delta (not kappa) opioid receptors in the RVLM, demonstrating endogenous opioid peptide release in the brain's blood pressure control center..

RPEP-00695PreliminaryAnimal Study

Generation of dynorphin knockout mice.

Sharifi, N · 2001

Prodynorphin knockout mice were viable and fertile with altered pain and reward responses, providing a definitive genetic tool for studying dynorphin's specific roles across pain, addiction, mood, and immune function..

RPEP-00706PreliminaryAnimal Study

Antisera against endogenous opioids increase the nocifensive response to formalin: demonstration of inhibitory beta-endorphinergic control.

Wu, H · 2001

ICV anti-beta-endorphin increased acute phase formalin pain, anti-leu-enkephalin increased late inflammatory phase pain, and anti-dynorphin affected both phases, demonstrating peptide-specific roles in endogenous pain modulation..

RPEP-00582PreliminaryAnimal Study

Role of brain dynorphin in nitrous oxide antinociception in mice.

Branda, E M · 2000

Intracerebroventricular dynorphin antibodies completely blocked nitrous oxide antinociception, proving that N2O analgesic effect is mediated by neuronal release of endogenous dynorphin activating kappa opioid receptors..

RPEP-00584PreliminaryAnimal Study

Antagonism of nitrous oxide antinociception in mice by intrathecally administered antisera to endogenous opioid peptides.

Cahill, F J · 2000

Intrathecal anti-dynorphin antibodies blocked nitrous oxide antinociception, while anti-enkephalin and anti-endorphin antibodies did not, confirming spinal dynorphin release mediates N2O analgesia at the spinal cord level..

RPEP-00595Preliminaryin-vitro

Interleukin-2: structural and biological relatedness to opioid peptides.

Jiang, C L · 2000

IL-2 contains a structural domain resembling opioid peptides around its 45th Tyr residue that mediates analgesic effects, blocked by anti-opioid antibodies, revealing molecular overlap between immune and opioid signaling..

RPEP-00596PreliminaryAnimal Study

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..

RPEP-00598PreliminaryAnimal Study

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..

RPEP-00601PreliminaryAnimal Study

Repeated ethanol administration induces short- and long-term changes in enkephalin and dynorphin tissue concentrations in rat brain.

Lindholm, S · 2000

Repeated ethanol produced both short-term (24h) and persistent (2-week) alterations in enkephalin and dynorphin tissue concentrations in mesolimbic reward regions, providing a neurochemical basis for alcohol craving and relapse..

RPEP-00609PreliminaryAnimal Study

Differential mechanisms mediating descending pain controls for antinociception induced by supraspinally administered endomorphin-1 and endomorphin-2 in the mouse.

Ohsawa, M · 2000

Endomorphin-2 produces analgesia through both direct mu-opioid receptor activation and indirect dynorphin A release activating kappa receptors via descending pain pathways, while endomorphin-1 uses only the mu pathway..

RPEP-00613PreliminaryAnimal Study

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..

RPEP-00616PreliminaryAnimal Study

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..

RPEP-00625PreliminaryAnimal Study

Involvement of dynorphin in immobilization stress-induced antinociception in the mouse.

Suh, H W · 2000

ICV and intrathecal anti-dynorphin antibodies blocked immobilization stress-induced analgesia, while anti-enkephalin and anti-endorphin antibodies did not, establishing dynorphin as the specific mediator at both brain and spinal levels..

RPEP-00631Preliminaryin-vitro

Opioid peptide gene expression primes cardiogenesis in embryonal pluripotent stem cells.

Ventura, C · 2000

Opioid peptide gene expression (prodynorphin, proenkephalin) preceded cardiac transcription factor activation (GATA-4, Nkx-2.5) during cardiogenesis in embryonic stem cells, suggesting opioid peptides prime heart cell development..

RPEP-00508PreliminaryAnimal Study

Growth hormone-releasing hormone and morphine attenuate growth hormone secretagogue-induced activation of the arcuate nucleus in the male rat.

Bailey, A R · 1999

GHRH pretreatment and morphine both attenuated GH secretagogue-induced Fos expression in the arcuate nucleus, demonstrating negative feedback and opioid-GH system crosstalk in GH secretagogue signaling..

RPEP-00511Preliminaryin-vitro

Dynorphin A processing enzyme: tissue distribution, isolation, and characterization.

Berman, Y · 1999

A prodynorphin processing enzyme was isolated and characterized, revealing tissue-specific processing that generates different bioactive dynorphin peptides in brain versus peripheral tissues like adrenal gland and gut..

RPEP-00531PreliminaryAnimal Study

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..

RPEP-00545Preliminaryin-vitro

Dynorphin A enhances mitogen-induced proliferative response and interleukin-2 production of rat splenocytes.

Ni, X · 1999

Dynorphin A enhanced mitogen-induced proliferation of rat splenocytes and increased IL-2 production, demonstrating immunostimulatory activity for this previously undercharacterized opioid peptide..

RPEP-00553PreliminaryReview

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..

RPEP-00446PreliminaryAnimal Study

Altered release of prostaglandins by opioids contributes to impaired cerebral hemodynamics following brain injury.

Al-Turki, A · 1998

Fluid percussion brain injury in newborn pigs impaired opioid-mediated cerebral artery dilation by disrupting prostaglandin release pathways, blunting the normal vasodilatory response..

RPEP-00467Preliminaryin-vitro

Glucose stimulation of pancreatic beta-cell lines induces expression and secretion of dynorphin.

Josefsen, K · 1998

Glucose stimulation induced prodynorphin gene expression in pancreatic beta-cell lines, with dynorphin peptides being processed and secreted, suggesting a novel opioid-mediated feedback mechanism in glucose regulation..

RPEP-00475Preliminaryin-vitro

Properties of mu 3 opiate alkaloid receptors in macrophages, astrocytes, and HL-60 human promyelocytic leukemia cells.

Makman, M H · 1998

The mu3 receptor on immune cells selectively binds opiate alkaloids (not endogenous opioid peptides), triggers nitric oxide release via constitutive nitric oxide synthase, and is present on macrophages, astrocytes, and leukemia cells..

RPEP-00489Preliminaryin-vitro

Beta-casomorphin-5 stimulates neurite outgrowth in a mouse neuroblastoma cell line (Neuro-2a).

Sakaguchi, M · 1998

Beta-casomorphin-5 stimulated neurite outgrowth in Neuro-2a cells at picomolar concentrations via mu-opioid receptors, demonstrated by naloxone reversibility and DAMGO replication of the effect..

RPEP-00494Preliminaryin-vitro

Characterization of immunoreactive dynorphin B and beta-endorphin in human plasma.

Silberring, J · 1998

Dynorphin B and beta-endorphin were confirmed in human plasma by HPLC and mass spectrometry, while dynorphin A was undetectable due to rapid enzymatic conversion to leu-enkephalin in blood..

RPEP-00503PreliminaryAnimal Study

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..

RPEP-00412PreliminaryAnimal Study

Immunoneutralization of beta-endorphin blocks prolactin release during suckling without affecting tuberoinfundibular dopaminergic neural activity.

Jaworski, R P · 1997

Anti-beta-endorphin antibodies blocked suckling-induced prolactin release without affecting tuberoinfundibular dopaminergic neurons, proving beta-endorphin is an essential mediator..

RPEP-00416PreliminaryAnimal Study

Effect of enkephalins and endorphins on cytotoxic activity of natural killer cells and macrophages/monocytes in mice.

Kowalski, J · 1997

All five tested opioid peptides enhanced both NK cell and macrophage/monocyte cytotoxic activity when administered by single IP injection in mice..

RPEP-00419PreliminaryAnimal Study

[Met5]enkephalin and delta2-opioid receptors in the spinal cord are involved in the cold water swimming-induced antinociception in the mouse.

Mizoguchi, H · 1997

Cold water swimming-induced analgesia is mediated by met-enkephalin acting on spinal delta-2 opioid receptors, as shown by selective receptor antagonist studies..

RPEP-00420Preliminaryin-vitro

Enkephalins modulate differentiation of normal human keratinocytes in vitro.

Nissen, J B · 1997

Enkephalins directly modulate the differentiation of normal human keratinocytes in vitro, establishing opioid peptides as regulators of skin cell biology..

RPEP-00432PreliminaryAnimal Study

Levels of dynorphin peptides in the central nervous system and pituitary gland of the spontaneously hypertensive rat.

Tan-No, K · 1997

Spontaneously hypertensive rats had significantly lower dynorphin A and B levels in the hypothalamus and pituitary compared to normotensive rats..

RPEP-00438Preliminaryin-vitro

Opioid peptide gene expression in the primary hereditary cardiomyopathy of the Syrian hamster. III. Autocrine stimulation of prodynorphin gene expression by dynorphin B.

Ventura, C · 1997

Dynorphin B induces dose-dependent autocrine stimulation of its own gene expression in cardiac myocytes, creating a self-amplifying loop that is exaggerated in cardiomyopathy..

RPEP-00440PreliminaryAnimal Study

[Met]enkephalin in the spinal cord is involved in the antinociception induced by intracerebroventricularly-administered etorphine in the mouse.

Xu, J Y · 1997

Intracerebroventricular etorphine increases met-enkephalin release in the spinal cord, and this spinal opioid mechanism accounts for a significant portion of the observed pain relief..

RPEP-00377Preliminaryin-vitro

Opioid peptide participates in post-tetanic twitch inhibition in guinea pig isolated ileum.

Ozaki, M · 1996

Endogenous opioid peptides contribute to post-tetanic inhibition of gut muscle contractions, and peptidase inhibitors enhance this effect by protecting naturally released peptides from degradation..

RPEP-00318Preliminaryin-vitro

Endogenous opioid peptides suppress cytokine-mediated upregulation of HIV-1 expression in the chronically infected promonocyte clone U1.

Chao, C C · 1995

Met-enkephalin, dynorphin, and kappa agonist U50,488 suppressed IL-6-induced HIV-1 expression by over 40% in chronically infected monocyte cells..

RPEP-00322Preliminaryin-vitro

[3H]naloxone binding sites in porcine ovarian follicles and corpora lutea during the ovarian cycle.

Hamada, H · 1995

Specific opioid receptors were found in pig granulosa cells and corpora lutea, with receptor numbers increasing during follicular maturation..

RPEP-00323Preliminaryin-vitro

Enhancement of phagocytosis by dynorphin A in mouse peritoneal macrophages.

Ichinose, M · 1995

Dynorphin A dose-dependently enhanced macrophage phagocytosis through a naloxone-insensitive (non-opioid receptor) mechanism..

RPEP-00327Preliminaryin-vitro

Effects of endogenous opioid peptides and their analogs on the activities of hypothalamic arcuate neurons in brain slices from diestrous and ovariectomized rats.

Lin, J Y · 1995

All tested opioid peptides inhibited arcuate neuron firing, with beta-endorphin affecting 55% of neurons, consistent across different hormonal states..

RPEP-00328PreliminaryAnimal Study

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..

RPEP-00336Preliminaryin-vitro

Processing of prodynorphin-derived peptides in striatal extracts. Identification by electrospray ionization mass spectrometry linked to size-exclusion chromatography.

Nylander, I · 1995

Dynorphin B was processed to leu-enkephalin at a 10,000-fold higher rate than dynorphin A in rat striatal extracts..

RPEP-00338Preliminaryin-vitro

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..

RPEP-00340Preliminaryin-vitro

Effects of ethanolic extracts from Eschscholtzia californica and Corydalis cava on dimerization and oxidation of enkephalins.

Reimeier, C · 1995

Eschscholtzia californica and Corydalis cava extracts inhibited peroxidase- and tyrosinase-mediated dimerization and oxidation of enkephalin peptides..

RPEP-00346Preliminaryin-vitro

Phorbol ester regulation of opioid peptide gene expression in myocardial cells. Role of nuclear protein kinase.

Ventura, C · 1995

Phorbol ester induced a concentration- and time-dependent increase in prodynorphin mRNA in cardiac myocytes, peaking at 4 hours and mediated through protein kinase C..

RPEP-00350PreliminaryAnimal Study

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..

RPEP-00286Preliminaryin-vitro

Delta-opioid receptor agonists inhibit neuromuscular transmission in human colon.

Chamouard, P · 1994

Delta opioid receptor agonists selectively inhibited nerve-stimulated contractions in human colon tissue without affecting spontaneous contractile activity..

RPEP-00287Preliminaryin-vitro

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..

RPEP-00290PreliminaryCross-Sectional

Endogenous opioid system and atrial natriuretic factor in normotensive offspring of hypertensive parents at rest and during exercise test.

Fontana, F · 1994

Normotensive offspring of hypertensive parents showed altered opioid-ANF interactions during exercise, suggesting early neurohumoral changes before hypertension onset..

RPEP-00292Preliminaryin-vitro

Augmenting effect of opioid peptides on murine macrophage activation.

Hagi, K · 1994

Dynorphin-A enhanced macrophage tumoricidal activity under suboptimal activation conditions but not when fully activated..

RPEP-00293PreliminaryAnimal Study

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..

RPEP-00296PreliminaryAnimal Study

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..

RPEP-00302Preliminaryin-vitro

Voltage-dependent effects of opioid peptides on hippocampal CA3 pyramidal neurons in vitro.

Moore, S D · 1994

Opioid peptides including dynorphins produced voltage-dependent changes in potassium currents in CA3 neurons, resolving contradictory findings from prior studies..

RPEP-00310PreliminaryAnimal Study

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..

RPEP-00311PreliminaryAnimal Study

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..

RPEP-00313Preliminaryin-vitro

Autoradiographic localization of beta-endorphin binding in the pancreas.

Zhang, M · 1994

Specific beta-endorphin binding sites were localized to pancreatic islet cells, blocked by mu and delta receptor ligands, confirming opioid receptors on insulin-producing cells..

RPEP-00260Preliminaryin-vitro

Pharmacological characterization of an opioid receptor in the ciliate Tetrahymena.

Chiesa, R · 1993

Tetrahymena has a functional opioid receptor that inhibits phagocytosis.

RPEP-00262Preliminaryin-vitro

Characterization of non-opioid [3H]dynorphin A-(1-13) binding sites in the rat heart.

Dumont, M · 1993

Rat heart has a non-opioid dynorphin A(1-13) binding site: Kd 285 nM, Bmax 215 pmol/mg protein.

RPEP-00270PreliminaryAnimal Study

Changes in the levels of several endogenous opioid peptides in dog cerebrospinal fluid following morphine administration.

Natsuki, R · 1993

Morphine produced distinct changes in multiple CSF opioid peptide species, with patterns differing from plasma changes.

RPEP-00271PreliminaryAnimal Study

Modulation of non-adrenergic non-cholinergic inhibitory transmission in rat duodenum: role of opiates and 5-hydroxytryptamine.

Postorino, A · 1993

Opioid peptides acting through all three receptor types (mu, delta, kappa) enhance non-adrenergic non-cholinergic inhibitory responses in the duodenum, while serotonin reduces them..

RPEP-00273PreliminaryAnimal Study

Chronic intracerebroventricular infusion of the antiopioid peptide, Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 (NPFF), downregulates mu opioid binding sites in rat brain.

Rothman, R B · 1993

Chronic ICV NPFF (5 micrograms/h for 10 days) downregulated mu opioid binding sites.

RPEP-00274PreliminaryAnimal Study

Phenylpiperidine opioid antagonists that promote weight loss in rats have high affinity for the kappa 2B (enkephalin-sensitive) binding site.

Rothman, R B · 1993

Weight-loss-promoting phenylpiperidine antagonists like LY255582 had high affinity for the kappa-2B binding site.

RPEP-00275PreliminaryAnimal Study

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.

RPEP-00277Preliminaryin-vitro

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..

RPEP-00281PreliminaryAnimal Study

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..

RPEP-00282PreliminaryAnimal Study

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..

RPEP-00283PreliminaryAnimal Study

Possible opioid receptor function changes in isolated atria of the spontaneously hypertensive rat.

Wong, S C · 1993

Leu-enkephalin at 0.2 micromolar increased spontaneous beating rate in SHR atria but not in normal rat atria, across ages 4 to 16 weeks..

RPEP-00284PreliminaryAnimal Study

Dynorphin modulates prolactin secretion in the turkey.

Youngren, O M · 1993

Big dynorphin (prodynorphin 209-240) caused a 5.1-fold increase in serum prolactin in turkeys, mediated through kappa opioid receptors..

RPEP-00221PreliminaryAnimal Study

Hypothalamic corticotropin-releasing hormone and opioid peptide neurons: functional changes after adrenalectomy and/or castration.

Almeida, O F · 1992

Adrenalectomy and castration independently and interactively regulated hypothalamic CRH mRNA, CRH peptide, opioid peptide content, and CRF-stimulated opioid release..

RPEP-00222PreliminaryAnimal Study

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.

RPEP-00226Preliminaryin-vitro

Selectivity and potency of opioid peptides in regulating human chorionic gonadotropin release from term trophoblast tissue.

Cemerikic, B · 1992

Order of potency for hCG release: kappa >>> mu > delta.

RPEP-00228Preliminaryin-vitro

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.

RPEP-00229PreliminaryAnimal Study

Effects of beta-endorphin on spontaneous uterine contractions. Prostaglandins production and 45Ca2+ uptake in uterine strips from ovariectomized rats.

Faletti, A · 1992

Beta-endorphin (10^-6 M) reduced uterine contractions, prostaglandin synthesis, and calcium uptake.

RPEP-00230PreliminaryAnimal Study

Interaction of opioid peptide-containing terminals with dopaminergic perikarya in the rat hypothalamus.

Fitzsimmons, M D · 1992

Electron microscopy demonstrated direct contact between opioid peptide-containing terminals and tyrosine hydroxylase-positive (dopaminergic) cell bodies in the rat hypothalamus..

RPEP-00231Preliminaryin-vitro

Kappa opioid agonists inhibit transmitter release from guinea pig hippocampal mossy fiber synaptosomes.

Gannon, R L · 1992

Kappa agonists U-62,066E and ethylketocyclazocine inhibited potassium-evoked glutamate and dynorphin B release from mossy fiber synaptosomes.

RPEP-00232PreliminaryAnimal Study

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..

RPEP-00234PreliminaryAnimal Study

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..

RPEP-00236PreliminaryAnimal Study

Dynorphin, a preferential ligand for kappa-opioid receptors, is present in nerve fibers and immune cells within inflamed tissue of the rat.

Hassan, A H · 1992

Dynorphin immunoreactivity detected in both inflammatory cells and cutaneous sensory nerve fibers in Freund's adjuvant-inflamed rat paw tissue..

RPEP-00237PreliminaryAnimal Study

Hippocampal opioid peptides and seizures.

Hong, J S · 1992

Both seizure types caused initial opioid release.

RPEP-00238PreliminaryAnimal Study

Endorphins do not affect behavioral stress responses in mice.

Katoh, A · 1992

ICV alpha-endorphin (2.5-10 nmol), beta-endorphin (0.38-1.5 nmol), and gamma-endorphin (2.5-10 nmol) did not affect conditioned suppression or forced swim immobility in mice..

RPEP-00239PreliminaryAnimal Study

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.

RPEP-00240PreliminaryAnimal Study

Dynorphin-(1-13): antinociceptive action and its effects on morphine analgesia and acute tolerance.

Kishioka, S · 1992

Dynorphin(1-13) ICV produced dose-dependent antinociception.

RPEP-00241PreliminaryAnimal Study

Age-related changes in opioid peptide concentrations in brain and pituitary of spontaneously hypertensive rats. Effect of antihypertensive drugs and comparison with deoxycorticosterone acetate and salt hypertension.

Li, S J · 1992

SHR rats had distinct age-dependent opioid peptide profiles in brain regions linked to blood pressure control.

RPEP-00242Preliminaryin-vitro

Characterization of opioid receptors mediating stimulation of adenylate cyclase activity in rat olfactory bulb.

Olianas, M C · 1992

Delta opioid receptors primarily mediate adenylate cyclase stimulation in olfactory bulb.

RPEP-00243PreliminaryAnimal Study

Inhibition of oestradiol-induced DNA synthesis by opioid peptides in the rat uterus.

Ordög, T · 1992

DMEPA (enkephalin analog) inhibited estradiol-induced uterine DNA synthesis by ~50% when given 1-2 hours before measurement.

RPEP-00245PreliminaryAnimal Study

Differential effects of opioid receptor agonists on nociception and cAMP level in the spinal cord of monoarthritic rats.

Przewłocka, B · 1992

Intrathecal mu and delta agonists produced enhanced antinociception in monoarthritic rats with greater cAMP inhibition.

RPEP-00250Preliminaryin-vitro

Reciprocal effects between opioid peptides and human polymorphonuclear leukocytes--II. Enhancement of phorbol myristate acetate-induced respiratory burst in human polymorphonuclear leukocyte by opioid peptides previously exposed to activated oxygen species.

Slaoui-Hasnaoui, A · 1992

Native opioid peptides did not affect PMN respiratory burst.

RPEP-00251Preliminaryin-vitro

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.

RPEP-00253PreliminaryAnimal Study

Modulation of peristalsis in the guinea-pig isolated small intestine by exogenous and endogenous opioids.

Waterman, S A · 1992

Exogenous opioids increased peristaltic threshold volume.

RPEP-00180PreliminaryAnimal Study

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.

RPEP-00181PreliminaryAnimal Study

Stereoselective effect of morphine on antinociception and endogenous opioid peptide levels in plasma but not cerebrospinal fluid of dogs.

Adams, M L · 1991

Active morphine raised blood levels of all four opioid peptides in dogs.

RPEP-00182PreliminaryAnimal Study

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.

RPEP-00184PreliminaryCross-Sectional

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.

RPEP-00185PreliminaryAnimal Study

Effect of opioid peptides on circular muscle of canine duodenum.

Bauer, A J · 1991

Met-enkephalin, leu-enkephalin, and dynorphin decreased inhibitory junction potentials in canine duodenal circular muscle via delta and mu receptors..

RPEP-00186PreliminaryAnimal Study

The effects of bilateral intranigral microinjection of selective opioid agonists on behavioral responses to noxious thermal stimuli.

Baumeister, A A · 1991

Mu-selective agonist DAGO injected into the substantia nigra produced antinociception comparable to the periaqueductal gray.

RPEP-00188PreliminaryAnimal Study

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..

RPEP-00189PreliminaryAnimal Study

Electrically-induced release of opioid peptides from the guinea-pig myenteric plexus preparation.

Corbett, A D · 1991

Pro-enkephalin fragments were released at 29-43% of tissue content loss.

RPEP-00190PreliminaryAnimal Study

Systemic administration of kainic acid differentially regulates the levels of prodynorphin and proenkephalin mRNA and peptides in the rat hippocampus.

Douglass, J · 1991

Kainic acid seizures increased hippocampal prodynorphin and proenkephalin mRNA while decreasing dynorphin A and met-enkephalin peptide levels, both proportional to seizure severity..

RPEP-00191PreliminaryAnimal Study

Up-regulation of opioid gene expression in spinal cord evoked by experimental nerve injuries and inflammation.

Draisci, G · 1991

Chronic constriction injury and inflammation both upregulated spinal preprodynorphin mRNA rapidly and sustainably.

RPEP-00192PreliminaryAnimal Study

Endogenous opioids tonically inhibit the depressor neurones in the caudal ventrolateral medulla of rabbits: mediation through delta- and kappa-receptors.

Drolet, G · 1991

Naloxone injection into the caudal ventrolateral medulla caused dose-dependent blood pressure drops.

RPEP-00194PreliminaryAnimal Study

mu-receptor mediates elevated glucose and corticosterone after third ventricle injection of opioid peptides.

Gunion, M W · 1991

Mu receptor agonists raised blood glucose and corticosterone.

RPEP-00195PreliminaryAnimal Study

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.

RPEP-00196PreliminaryAnimal Study

Neuropeptide regulation of feeding in dogs.

Inui, A · 1991

Pancreatic polypeptides and dynorphin A stimulated feeding in satiated dogs.

RPEP-00197PreliminaryAnimal Study

Increases in opioid-mediated swim antinociception following endopeptidase 24.15 inhibition.

Kest, B · 1991

Central administration of an endopeptidase 24.15 inhibitor enhanced opioid-mediated swim stress antinociception.

RPEP-00198PreliminaryAnimal Study

Regulation of proopiomelanocortin messenger RNA concentrations by opioid peptides in primary cell cultures of rat hypothalamus.

l'Héreault, S · 1991

Beta-endorphin inhibited POMC mRNA by 65% via delta receptors.

RPEP-00200PreliminaryAnimal Study

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.

RPEP-00201PreliminaryAnimal Study

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.

RPEP-00203Preliminaryin-vitro

Enkephalin hydrolysis by human serum biotinidase.

Oizumi, J · 1991

Human serum biotinidase hydrolyzes enkephalins and dynorphin A (<10-mer) with kcat/Km values similar to its biotin substrate biocytin..

RPEP-00204Preliminaryin-vitro

Naturally occurring opioid receptor agonists stimulate adenylate cyclase activity in rat olfactory bulb.

Onali, P · 1991

All three opioid peptides stimulated adenylate cyclase in olfactory bulb by ~40% above baseline.

RPEP-00205PreliminaryAnimal Study

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.

RPEP-00206PreliminaryAnimal Study

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.

RPEP-00207PreliminaryAnimal Study

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..

RPEP-00208PreliminaryAnimal Study

Effects of dexfenfluramine and opioid peptides, alone or in combination, on food intake and brain serotonin turnover in rats.

Robert, J J · 1991

Dexfenfluramine's anorectic effect dominated over opioid agonist feeding stimulation.

RPEP-00209PreliminaryAnimal Study

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.

RPEP-00211PreliminaryAnimal Study

Diethylstilbesterol- and pregnancy-induced changes in rat neurointermediate lobe oxytocin, arginine vasopressin, methionine enkephalin and dynorphin.

Schriefer, J A · 1991

Pregnancy and DES treatment altered pituitary met-enkephalin and dynorphin content in patterns paralleling oxytocin and vasopressin changes..

RPEP-00212PreliminaryAnimal Study

Prolonged inflammatory pain modifies corticotropin-releasing factor-induced opioid peptide release in the hypothalamus.

Shippenberg, T S · 1991

Chronic inflammation increased basal enkephalin release but abolished CRF-stimulated release of all three opioid peptides from the hypothalamus.

RPEP-00216PreliminaryAnimal Study

Endogenous opioid peptides and blood pressure regulation during controlled, stepwise hemorrhagic hypotension.

van den Berg, M H · 1991

Central and peripheral naloxone increased bleeding volumes before pressure dropped.

RPEP-00217PreliminaryAnimal Study

Effects of dynorphin A(1-13) and of fragments of beta-endorphin on blood pressure and heart rate of anesthetized rats.

van Giersbergen, P L · 1991

Full beta-endorphin caused naltrexone-reversible hypotension and bradycardia.

RPEP-00145PreliminaryAnimal Study

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.

RPEP-00146PreliminaryAnimal Study

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.

RPEP-00148Preliminaryin-vitro

Stimulation of hypothalamic opioid peptide release by lithium is mediated by opioid autoreceptors: evidence from a combined in vitro, ex vivo study.

Burns, G · 1990

Lithium releases all three opioid peptides by inhibiting autoreceptors.

RPEP-00149PreliminaryAnimal Study

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..

RPEP-00152Preliminaryin-vitro

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.

RPEP-00153Preliminaryin-vitro

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..

RPEP-00155PreliminaryAnimal Study

Spinal dynorphin A (1-17): possible mediator of antianalgesic action.

Fujimoto, J M · 1990

Dynorphin A(1-17) mediates an antianalgesic (pain-relief-opposing) system in the spinal cord.

RPEP-00156PreliminaryAnimal Study

Systemic single dose morphine pretreatment desensitizes mice to the spinal antianalgesic action of dynorphin A (1-17).

Fujimoto, J M · 1990

Single-dose morphine pretreatment desensitizes the spinal antianalgesic dynorphin system for up to 18 hours, possibly by triggering dynorphin release that leads to receptor desensitization..

RPEP-00157Preliminaryin-vitro

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.

RPEP-00159Preliminaryin-vitro

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.

RPEP-00160Preliminaryin-vitro

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..

RPEP-00161PreliminaryAnimal Study

Behavioral changes induced by stressful situations: effects of enkephalins, dynorphin, and their interactions.

Katoh, A · 1990

Enkephalin and dynorphin systems have opposing effects on stress behavior.

RPEP-00165Preliminaryin-vitro

Peptide opioids and morphine effects on inflammatory process.

Mazzone, A · 1990

Morphine has anti-inflammatory effects on granulocytes through both opioid receptor-dependent (aggregation, ATP) and independent (arachidonic acid metabolism) mechanisms.

RPEP-00166Preliminaryin-vitro

Specific binding of beta-endorphin to the isolated renal basolateral membranes in vitro.

Sato, H · 1990

Beta-endorphin binds to kidney membranes through both opioid (high-affinity, low-capacity) and non-opioid (low-affinity, high-capacity) sites.

RPEP-00168PreliminaryAnimal Study

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).

RPEP-00169PreliminaryAnimal Study

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..

RPEP-00173PreliminaryAnimal Study

Differentiation of acupuncture and nonacupuncture points by difference of associated opioids in the spinal cord in production of analgesia by acupuncture and nonacupuncture point stimulation, and relations between sodium and those opioids.

Takeshige, C · 1990

Acupuncture and non-acupuncture point stimulation produce analgesia through distinct opioid systems: met-enkephalin/mu pathway for acupuncture points, dynorphin/kappa pathway for non-acupuncture points..

RPEP-00174PreliminaryAnimal Study

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.

RPEP-00178PreliminaryAnimal Study

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..

RPEP-00179Preliminaryin-vitro

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..

RPEP-00102PreliminaryAnimal Study

Effects of beta-endorphin, met-enkephalin, and dynorphin A on basal and stimulated insulin secretion in the mouse.

Ahrén, B · 1989

Beta-endorphin had a dose-dependent biphasic effect on insulin secretion.

RPEP-00103PreliminaryCross-Sectional

Regional distribution of opioidergic nerves in human and canine prostates.

Aumüller, G · 1989

Prostatic opioid innervation comes exclusively from proenkephalin-derived peptides.

RPEP-00104PreliminaryReview

Ethanol ingestive behavior as a function of central neurotransmission.

Blum, K · 1989

The opioidergic system (beta-endorphin, enkephalin, dynorphin) is involved in both the pharmacological actions of alcohol and the craving/genetic predisposition toward alcohol abuse..

RPEP-00106PreliminaryAnimal Study

The involvement of opioid peptides in stress-induced analgesia in the slug Arion ater.

Dalton, L M · 1989

Stress-induced analgesia in slugs appears mediated by endogenous opioid peptides, particularly enkephalins and beta-endorphin.

RPEP-00107PreliminaryAnimal Study

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..

RPEP-00108Preliminaryin-vitro

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.

RPEP-00109PreliminaryAnimal Study

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..

RPEP-00111PreliminaryAnimal Study

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..

RPEP-00112PreliminaryReview

The effect of ethanol on the biosynthesis and regulation of opioid peptides.

Gianoulakis, C · 1989

Ethanol modifies the biosynthesis, post-translational processing, and release of all three opioid peptide families differently depending on acute versus chronic exposure..

RPEP-00113Preliminaryin-vitro

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.

RPEP-00114PreliminaryCross-Sectional

Opioid-like activity in the cerebrospinal fluid of pain patients treated by electroacupuncture.

Ho, W K · 1989

Electroacupuncture increased measurable opioid activity in spinal fluid, including beta-endorphin (80% of patients) and dynorphin (60% of patients), plus an unidentified opioid substance..

RPEP-00118PreliminaryCross-Sectional

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.

RPEP-00119PreliminaryCross-Sectional

Lidocaine treatment of painful diabetic neuropathy and endogenous opioid peptides in plasma.

Kastrup, J · 1989

Lidocaine increased plasma beta-endorphin equally in patients and controls, but pain relief in diabetic neuropathy was not correlated with beta-endorphin changes..

RPEP-00120PreliminaryAnimal Study

Central mu, delta, and kappa opioid binding sites, and brain and pituitary beta-endorphin and met-enkephalin in genetically obese (ob/ob) and lean mice.

Khawaja, X Z · 1989

Genetically obese mice showed massive increases in opioid peptide levels and shifts in receptor types, with kappa receptors up 2.7-fold and mu receptors down 40%..

RPEP-00122Preliminaryin-vitro

Computer analysis of the effect of beta-endorphin and dynorphin and related compounds on opioid binding to mouse brain membrane.

Landahl, H D · 1989

In a 4-site binding model, both beta-endorphin and dynorphin peptides preferred mu and delta sites, with dynorphin additionally interacting significantly with kappa sites..

RPEP-00123PreliminaryAnimal Study

Beta-endorphin and dynorphin mimic the circadian immunoenhancing and anti-stress effects of melatonin.

Maestroni, G J · 1989

Beta-endorphin and dynorphin replicated melatonin's immunoenhancing and anti-stress effects, but with complementary roles: beta-endorphin for normal conditions, dynorphin for stress states.

RPEP-00125PreliminaryAnimal Study

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.

RPEP-00126Preliminaryin-vitro

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..

RPEP-00127Preliminaryin-vitro

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..

RPEP-00129PreliminaryAnimal Study

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..

RPEP-00130Preliminaryin-vitro

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.

RPEP-00131Preliminaryin-vitro

Presynaptic auto- and allelo-receptor regulation of hypothalamic opioid peptide release.

Nikolarakis, K E · 1989

Opioid peptides regulate each other's release through presynaptic cross-receptor mechanisms.

RPEP-00132Preliminaryin-vitro

Molecular determinants of receptor affinity and selectivity of the natural delta-opioid agonist, dermenkephalin.

Sagan, S · 1989

The C-terminal residues Met6 and Asp7 of dermenkephalin are the primary determinants of delta-opioid receptor selectivity, overriding the mu-preferring N-terminal domain..

RPEP-00133PreliminaryAnimal Study

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.

RPEP-00135Preliminaryin-vitro

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.

RPEP-00136PreliminaryAnimal Study

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.

RPEP-00138PreliminaryAnimal Study

Intrathecal [Met5]enkephalin antibody blocks analgesia induced by intracerebroventricular beta-endorphin but not morphine in mice.

Tseng, L L · 1989

Beta-endorphin produces spinal analgesia by selectively releasing met-enkephalin.

RPEP-00139PreliminaryAnimal Study

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..

RPEP-00140PreliminaryAnimal Study

Participation of opiate receptors located in the nucleus tractus solitarii in the hypotension induced by alpha-methyldopa.

Van Giersbergen, P L · 1989

Alpha-methyldopa's hypotensive effect requires opioid receptor activation in the NTS, specifically through beta-endorphin and not through enkephalins or dynorphin..

RPEP-00141PreliminaryAnimal Study

Possible involvement of beta endorphin(1-31) and dynorphin(1-13) in the central hypotensive mechanism of action of alpha methyldopa.

van Giersbergen, P L · 1989

Both beta-endorphin(1-31) and dynorphin(1-13), but not met-enkephalin, mediate alpha-methyldopa's central hypotensive effect.

RPEP-00142PreliminaryAnimal Study

Possible involvement of brain opioid peptides in clonidine-induced hypotension in spontaneously hypertensive rats.

van Giersbergen, P L · 1989

Clonidine's central hypotensive mechanism involves beta-endorphin and dynorphin only in spontaneously hypertensive rats, not in normotensive Wistar-Kyoto rats..

RPEP-00144PreliminaryAnimal Study

Effects of opiates during baroreceptor and ergoreceptor induced changes in blood pressure.

Williams, C A · 1989

All three opioid peptide families selectively blocked the exercise pressor reflex (ergoreceptor) without affecting the baroreceptor reflex, suggesting a specific opioid-catecholamine pathway for exercise blood pressure responses..

RPEP-00065PreliminaryAnimal Study

Opioid peptides in pituitary gland, brain regions and peripheral tissues of spontaneously hypertensive and Wistar-Kyoto normotensive rats.

Bhargava, H N · 1988

Beta-endorphin was 49% higher in the pituitary of hypertensive rats (SHR) but dramatically lower in peripheral organs: 92% lower in heart, 48% lower in adrenals, and 57% lower in kidneys compared to normal rats (WKY).

RPEP-00066Preliminaryin-vitro

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.

RPEP-00067Preliminaryin-vitro

Tissue content of opioid peptides in the myenteric plexus-longitudinal muscle of guinea-pig small intestine.

Corbett, A D · 1988

The myenteric plexus (the nerve network that controls gut movement) of guinea pig small intestine contained a well-defined mix of opioid peptides. Met-enkephalin dominated at 405 pmol/g of tissue.

RPEP-00068PreliminaryAnimal Study

Effects of morphine and opioid peptides on plasma levels of atrial natriuretic peptide.

Crum, R L · 1988

Morphine injected into the brain (intracerebroventricular) was 10 times more potent than intravenous morphine at increasing plasma ANP (atrial natriuretic peptide), a hormone released by the heart that lowers blood pressure and promotes sodium excretion. Leu-enkephalin decreased plasma ANP concentrations, the opposite effect of morphine. Dynorphin and beta-endorphin (given either into the brain or into the vein) did not change ANP levels at all. All four opioids increased plasma norepinephrine and epinephrine (stress hormones), but morphine caused increases 10 to 50 times greater than the others. Ganglionic blockade (cutting the nerve connection from the brain to the heart) significantly reduced morphine's ability to increase ANP, confirming the effect requires an intact autonomic nervous system..

RPEP-00070PreliminaryReview

Hypothalamic mu-opioid receptors in cardiovascular control: a review.

Feuerstein, G · 1988

The three families of opioid peptides (dynorphins, endorphins, and enkephalins) all have cardiovascular effects.

RPEP-00071PreliminaryAnimal Study

Roles of central and peripheral mu, delta and kappa opioid receptors in the mediation of gastric acid secretory effects in the rat.

Fox, D A · 1988

Morphine and other mu-opioid agonists decreased gastric acid secretion.

RPEP-00072Preliminaryin-vitro

In vitro degradation of opioid peptides by human placental aminopeptidase M.

Furuhashi, M · 1988

Human placental aminopeptidase M completely degraded Met-enkephalin and Leu-enkephalin into their five constituent amino acids.

RPEP-00073Preliminaryin-vitro

Comparison of the pre-junctional effect of opioids in two blood vessels of the rabbit.

Gan, E A · 1988

In rabbit ear and saphenous (leg) arteries, both delta-selective opioid agonists (leu-enkephalin and met-enkephalin) and kappa-selective agonists (dynorphin-(1-13) and ethylketocyclazocine) inhibited nerve-stimulation-evoked contractions. Delta agonists showed a vessel-specific difference: their maximum inhibitory effect was significantly less in the saphenous artery than in the ear artery.

RPEP-00074PreliminaryAnimal Study

Involvement of mu opioid receptors in the amygdala in the control of feeding.

Gosnell, B A · 1988

The mu-selective opioid agonist DAGO (Tyr-D-Ala-Gly-(Me)Phe-Gly-ol) increased food intake when injected into the central nucleus of the amygdala at doses of 1 and 3 nanomoles. Neither DSLET (a delta-selective agonist) nor dynorphin A (a kappa-selective agonist) affected food intake at the same location, even at the highest dose of 3 nanomoles. Dynorphin A did increase food intake when injected into the medial hypothalamus at 2 nanomoles.

RPEP-00075Preliminaryin-vitro

Endogenous opiates do not influence glucose and lipid metabolism in rat adipocytes.

Hauner, H · 1988

Six opioid-related substances were tested on isolated rat adipocytes (fat cells): - Beta-endorphin, dynorphin, met-enkephalin, leu-enkephalin, and morphine (agonists) - Naloxone (antagonist) None altered insulin binding to fat cells.

RPEP-00076PreliminaryReview

Seizure-induced alterations in the metabolism of hippocampal opioid peptides suggest opioid modulation of seizure-related behaviors.

Hong, J S · 1988

After seizures (from electroshock, kainic acid, or kindling), both dynorphin and enkephalin initially decrease in the hippocampus, indicating release.

RPEP-00077PreliminaryAnimal Study

Prolactin release induced by opiate agonists, effect of glucocorticoid pretreatment in intact and adrenalectomized rats.

Kiem, D T · 1988

Cortisol at 25 mg/kg given 24 hours before testing decreased prolactin release triggered by all four opioid peptides (dynorphin, beta-endorphin, met-enkephalin, D-Met-Pro-enkephalinamide) injected into the brain. Actinomycin D pretreatment blocked cortisol's inhibitory effect.

RPEP-00078Preliminaryin-vitro

Opioids and cytosolic calcium in rat anterior pituitary: dynorphin preparation showed LHRH-like action due to contamination.

Knepel, W · 1988

A commercially purchased synthetic dynorphin A-(1-13) raised cytosolic calcium in rat pituitary cells.

RPEP-00083PreliminaryAnimal Study

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.

RPEP-00084Preliminaryin-vitro

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.

RPEP-00085PreliminaryAnimal Study

Further studies on opioids and hibernation: delta opioid receptor ligand selectively induced hibernation in summer-active ground squirrels.

Oeltgen, P R · 1988

DADLE (D-Ala2-D-Leu5 enkephalin), a delta-opioid receptor agonist, at 1.50 mg/kg/day induced summer hibernation comparable to that caused by natural Hibernation Induction Trigger (HIT). Morphine (1.50 mg/kg/day), morphiceptin (0.82 mg/kg/day), and dynorphin A (0.82 mg/kg/day) did not induce hibernation. Strikingly, morphine, morphiceptin, and dynorphin A actually antagonized HIT-induced hibernation.

RPEP-00086PreliminaryAnimal Study

Effects of naloxone and opioid agonists on gastric excitatory responses to stimulation of the vagus nerve in cats.

Okamoto, T · 1988

Naloxone (100 to 1000 micrograms/kg) did not affect the initial stomach response to vagus nerve stimulation.

RPEP-00087Preliminaryin-vitro

Regulation of human natural cytotoxicity by enkephalins and selective opiate agonists.

Oleson, D R · 1988

Met-enkephalin, leu-enkephalin, dynorphin (1-13), DSLET (delta agonist), and DAGO (mu agonist) were tested on human NK cells from healthy donors after 18-hour incubation. The results were bidirectional: populations with low baseline NK activity showed enhancement.

RPEP-00088PreliminaryAnimal Study

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.

RPEP-00089PreliminaryAnimal Study

The difference in stress-induced analgesia in C57BL/6 and DBA/2 mice: a search for biochemical correlates.

Przewłocka, B · 1988

DBA mice had higher baseline pain thresholds than C57 mice.

RPEP-00090PreliminaryAnimal Study

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.

RPEP-00091PreliminaryAnimal Study

In vivo evidence for the specific binding of human beta-endorphin to the lung and liver of the rat.

Sato, H · 1988

Radioactive beta-endorphin injected intravenously accumulated specifically in the lung and liver but not other tissues.

RPEP-00092Preliminaryin-vitro

Characterization of opioid receptors on isolated canine gallbladder smooth muscle cells.

Severi, C · 1988

Three opioid peptides caused dose-dependent contraction of isolated gallbladder muscle cells: met-enkephalin > dynorphin(1-13) > leu-enkephalin. The contractions were blocked by the opioid antagonists naloxone and MR2266 but not by muscarinic, CCK/gastrin, or tachykinin antagonists.

RPEP-00093PreliminaryAnimal Study

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.

RPEP-00094PreliminaryAnimal Study

Differential effects of opioid peptides administered intracerebrally in loci of self-stimulation reward of lateral hypothalamus and ventral tegmental area--substantia nigra.

Singh, J · 1988

Leu-enkephalin and leu-enkephalinamide inhibited electrical self-stimulation in the substantia nigra/ventral tegmental area (SN-VTA) but not the medial forebrain bundle/lateral hypothalamus (MFB-LH).

RPEP-00095PreliminaryAnimal Study

Antinociceptive action of intracerebroventricularly administered dynorphin and other opioid peptides in the rat.

Tiseo, P J · 1988

Dynorphin A produced dose-related, naloxone-reversible analgesia via intracerebroventricular injection, confirming its function as an endogenous opioid painkiller acting through kappa receptors..

RPEP-00096PreliminaryAnimal Study

Characterization of opioid peptide-like anticonvulsant activity in rat cerebrospinal fluid.

Tortella, F C · 1988

CSF from rats that had just experienced an electroshock seizure significantly raised seizure thresholds in recipient rats when injected into their brain ventricles. This anticonvulsant activity was blocked by high-dose naloxone and by the selective delta-opioid antagonist ICI 174,864.

RPEP-00097PreliminaryAnimal Study

Cold swim stress-induced changes in the levels of opioid peptides in the rat CNS and peripheral tissues.

Vaswani, K K · 1988

Cold swim stress caused opposite changes in opioid peptide levels depending on the body region.

RPEP-00099PreliminaryAnimal Study

Co-localization of proenkephalin- and prodynorphin-derived opioid peptides in laminae IV/V spinal neurons revealed in arthritic rats.

Weihe, E · 1988

Chronic arthritis triggered spinal cord neurons to produce peptides from two different opioid precursor families in the same cells.

RPEP-00045PreliminaryAnimal Study

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.

RPEP-00046PreliminaryAnimal Study

Mu-, delta-, kappa- and epsilon-opioid receptor modulation of the hypothalamic-pituitary-adrenocortical (HPA) axis: subchronic tolerance studies of endogenous opioid peptides.

Iyengar, S · 1987

All four tested opioid peptides (beta-endorphin, dynorphin, MEAP, and DADLE) increased plasma corticosterone (a stress hormone) in normal rats.

RPEP-00049PreliminaryAnimal Study

Diurnal variation in prolactin, adrenocorticotropin and corticosterone release induced by opiate agonists in intact and adrenalectomized rats.

Kiem, D T · 1987

Beta-endorphin (0.5 microgram injected into the brain), dynorphin (1 microgram), and U50-488H (a kappa opioid drug, 10 mg/kg) all stimulated prolactin (PRL) release more in the afternoon (4-5 PM) than in the morning (8-9 AM). Morphine (10 mg/kg subcutaneous), met-enkephalin (200 micrograms), and D-Met-Pro-Enk (0.5 microgram) did not show this daily rhythm.

RPEP-00050PreliminaryAnimal Study

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.

RPEP-00051PreliminaryAnimal Study

Alterations in regional concentrations of endogenous opioids following traumatic brain injury in the cat.

McIntosh, T K · 1987

Severe brain injury (3.0 to 4.0 atmospheres of pressure) caused dynorphin to increase significantly in five brain regions: striatum, frontal cortex, parietal cortex, pons, and medulla.

RPEP-00053PreliminaryAnimal Study

An analysis of the 'tolerance' which develops to analgetic electrical stimulation of the midbrain periaqueductal grey in freely moving rats.

Millan, M J · 1987

Electrical stimulation of the periaqueductal grey (PAG, a brain region that controls pain) initially produced strong pain relief in rats.

RPEP-00054Preliminaryin-vitro

Partial characterization of a novel endogenous opioid in human cerebrospinal fluid.

Miller, B E · 1987

Human cerebrospinal fluid (CSF) from pain-free surgery patients contained Peak B at a concentration equivalent to about 1.4 picomoles of morphine per milliliter. Injected into mouse brains, Peak B produced dose-dependent pain relief at 0.06 and 0.12 picomoles of morphine equivalents.

RPEP-00061Preliminaryin-vitro

Combined high-performance liquid chromatographic-radioimmunoassay method for the analysis of endorphins, enkephalins and other neurotransmitter peptides.

Venn, R F · 1987

The new method combined HPLC (high-performance liquid chromatography) with radioimmunoassay (RIA) to measure opioid peptides in human cerebrospinal fluid, plasma, and tissues. The key advantage: HPLC first separates beta-endorphin from its precursor beta-lipotropin and from other opioid peptides.

RPEP-13153lowAnimal Study

Dopaminergic and Opioid Systems Interact to Produce Peripheral Antinociception in Mice.

Queiroz, Bárbara F G · 2025

Peripheral dopamine and opioid systems interact synergistically to inhibit nociception in mice through local receptor and peptide mechanisms..

RPEP-05397lowin vitro

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..

RPEP-05403n/a (review)Review

New Perspectives in the Pathophysiology and Treatment of Pain in Patients with Dry Eye Disease.

Giannaccare, Giuseppe · 2021

Eye pain in dry eye disease is modulated by endogenous opioid peptides.

RPEP-05506n/a-reviewReview

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..