GHRP-6
Growth Hormone Releasing Peptide-6, Growth hormone-releasing hexapeptide, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2
Food intake and interdigestive gastrointestinal motility in ghrelin receptor mutant rats.
Bülbül. Mehmet M; Babygirija. Reji R; Zheng. Jun J; Ludwig. Kirk K; Xu. Haiyan H; Lazar. Jozef J; Takahashi. Toku T
Key Findings
- Rats with a truncated GHSR (ghrelin receptor) do not increase food intake when given ghrelin, though baseline intake is unchanged.
- In wild‑type rats, ghrelin enhances phase III‑like gastric and duodenal contractions, an effect blocked by the GHSR antagonist (D‑lys3)GHRP‑6.
- Spontaneous phase III‑like gastric contractions persist in mutant rats, indicating compensatory mechanisms independent of the ghrelin receptor.
Practical Outcomes
- For the biohacking community, this study reinforces that the ghrelin‑GHSR pathway drives hunger and gut motility, so agonist peptides like GHRP‑6 may boost appetite and gastric activity. However, the work uses a receptor‑blocking version of GHRP‑6 in rats, so it offers limited direct guidance for dosing or protocols in humans. It mainly confirms existing ideas rather than providing new actionable strategies.
Summary
Scientists made rats with a broken ghrelin receptor and found that ghrelin no longer makes them eat more, but their normal eating stays the same. In normal rats, ghrelin boosts stomach and duodenum contraction waves, and a drug that blocks the receptor (a version of GHRP‑6) stops this effect. Even without a working receptor, the rats still have some natural contraction waves, suggesting the body has backup ways to keep the gut moving.
Abstract
Ghrelin is the endogenous ligand for the growth hormone secretagogue receptor (GHSR). Ghrelin regulates feeding activity and interdigestive contractions of the stomach in rodents. To investigate the role of endogenous ghrelin in the digestive system, we have developed GHSR-mutant rats, named FHH-Ghsr(m1Mcwi), using the Fawn-Hooded Hypertensive (FHH) parental strain. N-ethyl-N-nitrosourea (ENU) was used as a mutagen. Genomic DNA prepared from a tail clip was analyzed using the targeting induced local lesions in genomes (TILLING) approach. The non-synonymous mutation in position 343 (NM_032075) led to the generation of a premature stop codon, causing deletion of the last 22 amino acids at the C-terminal of ghrelin receptor protein. Spontaneous and ghrelin-stimulated food intake was measured in wild-type (WT) FHH and FHH-Ghsr(m1Mcwi) rats. For interdigestive motility recording, two strain gauge transducers were sutured on the antrum and duodenum. Spontaneous gastroduodenal contractions were recorded in freely moving conscious rats. Ghrelin (40 μg/kg) failed to stimulate food intake in the mutant rats, while spontaneous food intake was not significantly different between the WT rats and FHH-Ghsr(m1Mcwi) rats. Phase III-like contractions were observed in stomach and duodenum both in the WT and FHH-Ghsr(m1Mcwi) rats. In the WT rats, ghrelin (12 μg/kg) administration enhanced spontaneous phase III-like contractions, and a GHSR antagonist, (D-lys3)GHRP-6 (0.28 mg/kg), abolished the spontaneous phase III-like contractions. In FHH-Ghsr(m1Mcwi) rats, ghrelin and (D-lys3)GHRP-6 did not affect phase III-like contractions. It is suggested that the intact GHSR structure is essential for the ghrelin-dependent regulation of interdigestive motility and feeding behavior. Even in FHH-Ghsr(m1Mcwi) rats, spontaneous gastric phase III-like contractions were still observed, suggesting the development of a compensatory mechanism to maintain these contractions.
Study Information
pubmed
2011
2011-01-22T00:00:00.000Z
10.1007/s00535-010-0366-6
23
42