Browse more peptide research, methods and limitations.
Female ICU patients maintained higher GH pulse frequency and IGF-1 levels than males during protracted critical illness, with gender-modulated responses to GHRP-2/GHRH stimulation, potentially explaining women's better ICU survival.
Van den Berghe, G; Baxter, R C; Weekers, F; Wouters, P; Bowers, C Y; Veldhuis, J D · Clinical Trial
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.
Ventura, C; Maioli, M · In Vitro
GHRP-2 pretreatment directly protected against diastolic myocardial stunning in isolated hearts, while recombinant GH did not, demonstrating GH-independent, direct cardiac protection through cardiac GH secretagogue receptors.
Weekers, F; Van Herck, E; Isgaard, J; Van den Berghe, G · Animal Study
Exercise attenuated L-arginine + GHRP-2 synergistic GH release in men but not women, revealing gender-specific modulation of GH secretagogue synergy by physical activity.
Wideman, L; Weltman, J Y; Patrie, J T; Bowers, C Y; Shah, N; Story, S; Veldhuis, J D; Weltman, A · RCT
L-arginine and GHRP-2 produced synergistic (not just additive) GH release at rest, with women showing greater absolute GH responses than men, supporting combined use for maximal GH stimulation.
Wideman, L; Weltman, J Y; Patrie, J T; Bowers, C Y; Shah, N; Story, S; Weltman, A; Veldhuis, J D · RCT
Multiple host-defense peptides including lactoferricin and magainin-related peptides directly inactivated HSV-1 and HSV-2 in a validated microplate screening assay, expanding their known antimicrobial spectrum to include antiviral activity.
Yasin, B; Pang, M; Turner, J S; Cho, Y; Dinh, N N; Waring, A J; Lehrer, R I; Wagar, E A · In Vitro
Thymosin alpha-1 improved virological (HBV DNA clearance) and biochemical (ALT normalization) responses in anti-HBe positive chronic hepatitis B, a treatment-resistant subgroup.
Zavaglia, C; Severini, R; Tinelli, C; Franzone, J S; Airoldi, A; Tempini, S; Bettale, G; Ideo, G · RCT
GHRP-6 and the oral GHS NN703 concentrated in rat gastric tissue containing ghrelin-producing cells, suggesting GH secretagogues may act partly by stimulating endogenous ghrelin release as a secondary mechanism.
Ahnfelt-Rønne, I; Nowak, J; Olsen, U B · Animal Study
Thymosin alpha-1 demonstrates clinical efficacy in chronic hepatitis B and C (combined with interferon), with emerging evidence for cancer immunotherapy, HIV, and vaccine enhancement, showing excellent tolerability.
Ancell, C D; Phipps, J; Young, L · Review
Three months of ipamorelin (SC injection) counteracted methylprednisolone-induced decreases in bone formation rate, bone mineral content, and partially preserved skeletal muscle mass in adult female rats.
Andersen, N B; Malmlöf, K; Johansen, P B; Andreassen, T T; Ørtoft, G; Oxlund, H · Animal Study
Estradiol replacement selectively relieved GH autonegative feedback on GHRP-2-stimulated (not GHRH-stimulated) GH secretion in postmenopausal women, demonstrating pathway-specific estrogen modulation of the somatotropic axis.
Anderson, S M; Wideman, L; Patrie, J T; Weltman, A; Bowers, C Y; Veldhuis, J D · RCT
Thymosin alpha-1 + IFN-alpha shifted Th1/Th2 balance toward Th1 dominance (increased IFN-γ/IL-2, decreased IL-4/IL-10) in HCV patient PBMCs, while IFN-alpha alone produced only partial Th1 enhancement.
Andreone, P; Cursaro, C; Gramenzi, A; Margotti, M; Ferri, E; Talarico, S; Biselli, M; Felline, F; Tuthill, C; Martins, E; Gasbarrini, G; Bernardi, M · In Vitro
Ghrelin stimulated food intake and weight gain in rats through vagal and hypothalamic mechanisms, with ghrelin levels suppressed by feeding and increased by leptin, establishing the ghrelin-leptin axis for appetite regulation.
Asakawa, A; Inui, A; Kaga, T; Yuzuriha, H; Nagata, T; Ueno, N; Makino, S; Fujimiya, M; Niijima, A; Fujino, M A; Kasuga, M · Animal Study
Neuropeptides — particularly tachykinins (substance P, neurokinin A) and calcitonin gene-related peptide (CGRP) — are released from sensory nerves in the airways through axon reflexes and local nerve activation. In rodent models, this neurogenic inflammation clearly contributes to responses against allergens, infections, and irritants. However, direct evidence for sensory neuropeptide involvement in human airway disease is lacking, and initial clinical studies using strategies to block neurogenic inflammation have not shown encouraging results.
Barnes, P J ·
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.
Befort, K; Filliol, D; Decaillot, F M; Gaveriaux-Ruff, C; Hoehe, M R; Kieffer, B L · In Vitro
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.
Berman, Y; Mzhavia, N; Polonskaia, A; Devi, L A · Animal Study
TFA contamination from peptide synthesis inactivated thymosin alpha-1's clonal growth inhibition activity, demonstrating the need for rigorous purification and biological activity testing of therapeutic peptide preparations.
Bianco-Batlles, D; Naylor, C W; Moshier, J A; Dosescu, J; Naylor, P H · In Vitro
BPC-157, omeprazole, and bromocriptine healed haloperidol-induced gastric lesions, while atropine, lansoprazole, and cimetidine failed, demonstrating the lesions are dopamine-mediated and BPC-157 acts through dopaminergic mechanisms.
Bilic, I; Zoricic, I; Anic, T; Separovic, J; Stancic-Rokotov, D; Mikus, D; Buljat, G; Ivankovic, D; Aralica, G; Prkacin, I; Perovic, D; Mise, S; Rotkvic, I; Petek, M; Rucman, R; Seiwerth, S; Sikiric, P · Animal Study
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.
Cabot, Peter J; Carter, Laurenda; Schäfer, Michael; Stein, Christoph · Animal Study
Functional ghrelin and synthetic GHS receptors were identified on human breast, prostate, and lung cancer cells, with receptor subtypes potentially different from those in normal pituitary tissue.
Cassoni, P; Papotti, M; Ghè, C; Catapano, F; Sapino, A; Graziani, A; Deghenghi, R; Reissmann, T; Ghigo, E; Muccioli, G · In Vitro
BNP was the strongest predictor of left ventricular hypertrophy and cardiac mortality in 112 ESRD dialysis patients, outperforming ANP for cardiovascular risk stratification in this high-risk population.
Cataliotti, A; Malatino, L S; Jougasaki, M; Zoccali, C; Castellino, P; Giacone, G; Bellanuova, I; Tripepi, R; Seminara, G; Parlongo, S; Stancanelli, B; Bonanno, G; Fatuzzo, P; Rapisarda, F; Belluardo, P; Signorelli, S S; Heublein, D M; Lainchbury, J G; Leskinen, H K; Bailey, K R; Redfield, M M; Burnett, J C · Cross Sectional
Acute vasopeptidase inhibition in experimental mild heart failure raised ANP/BNP, increased renal sodium excretion, suppressed aldosterone, and avoided renin-angiotensin activation — harnessing endogenous peptide defenses.
Chen, H H; Lainchbury, J G; Matsuda, Y; Harty, G J; Burnett, J C · Animal Study
MK-677 at 10 and 25 mg/day increased GH and IGF-1 dose-dependently over 4 weeks in GH-deficient adults with acceptable safety, supporting its potential as oral GH replacement therapy.
Codner, E; Cassorla, F; Tiulpakov, A N; Mericq, M V; Avila, A; Pescovitz, O H; Svensson, J; Cerchio, K; Krupa, D; Gertz, B J; Murphy, G · Clinical Trial
Vasopeptidase inhibitors simultaneously enhance protective natriuretic peptides/bradykinin and block harmful angiotensin II, showing superior cardiovascular benefits over ACE inhibitors alone, despite angioedema risk as a limitation.
Corti, R; Burnett, J C; Rouleau, J L; Ruschitzka, F; Lüscher, T F · Review
Somatostatin octapeptides (lanreotide, octreotide, vapreotide) showed significant binding to GHRP receptors in human pituitary membranes, revealing unexpected cross-reactivity between somatostatin and GH secretagogue receptor systems.
Deghenghi, R; Papotti, M; Ghigo, E; Muccioli, G; Locatelli, V · In Vitro
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.
Fontana, F; Bernardi, P; Tartuferi, L; Boschi, S; Di Toro, R; Spampinato, S · Cross Sectional
Pro-BNP and NT-proBNP are strong biochemical markers for heart failure with practical advantages over mature BNP, including longer stability and higher circulating levels, supporting their clinical adoption.
Gøtze, J P; Kastrup, J · Review
NN703-ipamorelin hybrid GH secretagogues showed low nanomolar in vitro potency in pituitary cell assays and effective GH release in pigs in vivo, validating the hybrid design approach.
Hansen, T K; Ankersen, M; Raun, K; Hansen, B S · In Vitro
Oral GHRP-2 stimulated GH release in adult goats when absorbed through the intestines (not rumen), demonstrating post-gastric oral peptide bioactivity in adult large animals with mature digestive systems.
Hashizume, T; Tanabe, Y; Ohtsuki, K; Mori, A; Matsumoto, N; Hara, S · Animal Study
Appetite regulation involves two integrated time scales: acute meal-by-meal gut peptide signals (CCK, GLP-1, ghrelin, PYY) and chronic body weight signals (leptin, insulin), converging on hypothalamic and brainstem integration centers.
Havel, P J · Review
Heart failure involves coordinated activation of multiple neurohormonal systems, and measuring these provides diagnostic, prognostic, and therapeutic guidance, with BNP/NT-proBNP showing the strongest clinical utility.
Kjaer, A; Hesse, B · Review
Adrenomedullin contributes to both phases of sepsis: beneficial vasodilation during early compensation and harmful cardiovascular collapse during late decompensation, driven by progressive ADM accumulation from reduced clearance and increased tissue production.
Koo, D J; Zhou, M; Chaudry, I H; Wang, P · Review
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.
Li, P; Tjen-A-Looi, S; Longhurst, J C · Animal Study
Oral CP-424,391 (25 mg/kg/day for 7 days) reduced myocardial infarct size by ~50% in an in-vivo rabbit ischemia-reperfusion model, demonstrating significant cardioprotection from an orally available GH secretagogue.
MacAndrew, J T; Ellery, S S; Parry, M A; Pan, L C; Black, S C · Animal Study
Long-term NEP inhibition (2 weeks) in heart failure rats improved cardiac function, reduced ventricular remodeling, and paradoxically lowered ANP/BNP — the decrease reflecting improved cardiac status rather than drug failure.
Maki, T; Nasa, Y; Yamaguchi, F; Yoshida, H; Mori, M; Takada, T; Horikawa, E; Okano, K; Takeo, S · Animal Study
Optimized ghrelin tetrapeptide derivatives showed structural similarity to synthetic peptidyl GH secretagogues like GHRP-1, demonstrating convergent molecular solutions between the natural ligand and designed drugs.
Matsumoto, M; Kitajima, Y; Iwanami, T; Hayashi, Y; Tanaka, S; Minamitake, Y; Hosoda, H; Kojima, M; Matsuo, H; Kangawa, K · In Vitro
In 1,640 randomly sampled urban adults, BNP predicted mortality from left ventricular dysfunction, supporting population-level screening with natriuretic peptides to identify undiagnosed cardiac disease.
McDonagh, T A; Cunningham, A D; Morrison, C E; McMurray, J J; Ford, I; Morton, J J; Dargie, H J · Cohort
Topical BPC-157 cream accelerated burn wound healing (faster re-epithelialization and contraction) while simultaneously attenuating distant burn-associated gastric lesions in mice, demonstrating both local and systemic effects from topical application.
Mikus, D; Sikiric, P; Seiwerth, S; Petricevic, A; Aralica, G; Druzijancic, N; Rucman, R; Petek, M; Pigac, B; Perovic, D; Kolombo, M; Kokic, N; Mikus, S; Duplancic, B; Fattorini, I; Turkovic, B; Rotkvic, I; Mise, S; Prkacin, I; Konjevoda, P; Stambuk, N; Anic, T · Animal Study
125I-ghrelin bound to human hypothalamus and pituitary with high affinity but showed different binding characteristics than synthetic GHS (hexarelin, MK-0677), suggesting distinct receptor interaction modes or subtypes.
Muccioli, G; Papotti, M; Locatelli, V; Ghigo, E; Deghenghi, R · In Vitro
MK-677 combined with alendronate maintained higher bone formation markers than alendronate alone over 12 months in postmenopausal women, demonstrating complementary mechanisms: IGF-1-stimulated bone building plus anti-resorptive bone protection.
Murphy, M G; Weiss, S; McClung, M; Schnitzer, T; Cerchio, K; Connor, J; Krupa, D; Gertz, B J · RCT
SM-130686, a structurally novel oxindole GH secretagogue, showed potent in-vitro and in-vivo GH-releasing activity, increased IGF-1 and body weight in rats, and was orally active, demonstrating a new chemical class for GHS-R targeting.
Nagamine, J; Nagata, R; Seki, H; Nomura-Akimaru, N; Ueki, Y; Kumagai, K; Taiji, M; Noguchi, H · Animal Study
Three weeks of twice-daily ghrelin injections improved multiple measures of heart function in rats with heart failure caused by coronary artery ligation. Ghrelin-treated heart failure rats had significantly higher cardiac output (315 vs 266 mL/min/kg, P<0.05), stronger heart contractions (dP/dtmax 5,738 vs 4,363 mmHg/s, P<0.05), and improved fractional shortening (19% vs 15%, P<0.05) compared to placebo-treated heart failure rats. Ghrelin also attenuated cardiac cachexia — the dangerous muscle wasting that accompanies heart failure. Treated rats gained 10% body weight versus only 3% for placebo. Additionally, ghrelin inhibited left ventricular enlargement (remodeling) and increased the thickness of surviving heart muscle. These benefits occurred alongside significantly elevated growth hormone and IGF-1 levels.
Nagaya, N; Uematsu, M; Kojima, M; Ikeda, Y; Yoshihara, F; Shimizu, W; Hosoda, H; Hirota, Y; Ishida, H; Mori, H; Kangawa, K · Preclinical (Animal Study)
In 12 patients with chronic heart failure, IV ghrelin infusion at 0.1 µg/kg/min produced significant hemodynamic improvements compared to placebo: • Mean arterial pressure decreased by 9 mmHg (p<0.05) • Cardiac index increased by 25% (p<0.05) • Stroke volume index increased by 30% (p<0.05) • Heart rate did not significantly change • Pulmonary arterial pressure and pulmonary capillary wedge pressure were not significantly altered Ghrelin also triggered a 15-fold increase in serum growth hormone levels, with slight increases in epinephrine, ACTH, cortisol, and prolactin. Kidney function markers — urine volume, sodium excretion, and creatinine clearance — were unaffected. Placebo infusion produced no changes in any parameter.
Nagaya, N; Miyatake, K; Uematsu, M; Oya, H; Shimizu, W; Hosoda, H; Kojima, M; Nakanishi, N; Mori, H; Kangawa, K ·
In 1,637 postmenopausal women with prior vertebral fractures treated for a median of 21 months: **Fracture reduction:** - New vertebral fractures: 14% (placebo) vs 5% (20 μg) vs 4% (40 μg) - Relative risk reduction: 65% (20 μg) and 69% (40 μg) for vertebral fractures - Nonvertebral fragility fractures: 6% (placebo) vs 3% (both PTH groups) — 53-54% relative risk reduction **Bone density gains vs placebo:** - Lumbar spine: +9 percentage points (20 μg), +13 percentage points (40 μg) - Femoral neck: +3 percentage points (20 μg), +6 percentage points (40 μg) - Total body bone mineral: +2 to 4 percentage points The 40 μg dose increased bone density more but didn't reduce fractures more than 20 μg, and had more side effects. The 40 μg dose also decreased bone density at the radial shaft by 2 percentage points.
Neer, R M; Arnaud, C D; Zanchetta, J R; Prince, R; Gaich, G A; Reginster, J Y; Hodsman, A B; Eriksen, E F; Ish-Shalom, S; Genant, H K; Wang, O; Mitlak, B H ·
Gut peptides (ghrelin, CCK, GLP-1, PYY) regulate appetite through neural and hormonal pathways that are significantly disrupted by gastrointestinal surgery, requiring surgical awareness for optimal patient management.
Näslund, E; Hellström, P M; Kral, J G · Review
Thymosin alpha-1 restored T-cell proliferation, NK cell cytotoxicity, and Th1 cytokine production (IL-2, IFN-γ) in cyclophosphamide-immunosuppressed mice, demonstrating broad immune reconstitution capacity.
Ohmori, H; Kamo, M; Yamakoshi, K; Nitta, M H; Hikida, M; Kanayama, N · Animal Study
Spiro(indoline-piperidine) small molecules mimicking ghrelin's N-terminal active core showed potent GHS-R binding and functional calcium signaling activation, validating small-molecule ghrelin mimicry.
Palucki, B L; Feighner, S D; Pong, S; McKee, K K; Hreniuk, D L; Tan, C; Howard, A D; Van der Ploeg, L H; Patchett, A A; Nargund, R P · In Vitro
BPC-157 provided sustained chronic cytoprotection against alcohol-induced gastric lesions, with effectiveness maintained throughout prolonged alcohol exposure alongside liver protection documented in companion study.
Prkacin, I; Aralica, G; Perovic, D; Separovic, J; Gjurasin, M; Lovric-Bencic, M; Stancic-Rokotov, D; Ziger, T; Anic, T; Sikiric, P; Seiwerth, S; Staresinic, M; Mise, S; Rotkvic, I; Jagic, V; Rucman, R; Petek, M; Turkovic, B; Marovic, A; Sjekavica, I; Sebecic, B; Boban-Blagaic, A; Ivasovic, Z · Animal Study
BPC-157 both prevented (when co-administered) and reversed (when given after damage) chronic alcohol-induced portal hypertension and liver lesions in rats, measured by direct portal vein pressure and histological assessment.
Prkacin, I; Separovic, J; Aralicia, G; Perovic, D; Gjurasin, M; Lovric-Bencic, M; Stancic-Rokotov, D; Staresinic, M; Anic, T; Mikus, D; Sikiric, P; Seiwerth, S; Mise, S; Rotkvic, I; Jagic, V; Rucman, R; Petek, M; Turkovic, B; Marovic, A; Sebecic, B; Boban-Blagaic, A; Kokic, N · Animal Study
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.
Przewłocki, R; Przewłocka, B · Review