GHRP-6
Growth Hormone Releasing Peptide-6, Growth hormone-releasing hexapeptide, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2
Endogenous ghrelin and 5-HT regulate interdigestive gastrointestinal contractions in conscious rats.
Taniguchi. Hiroshi H; Ariga. Hajime H; Zheng. Jun J; Ludwig. Kirk K; Mantyh. Christopher C; Pappas. Theodore N TN; Takahashi. Toku T
Key Findings
- Blocking the ghrelin receptor with (d‑lys3)GHRP‑6 reduces the frequency and strength of stomach (antral) phase‑III‑like contractions in rats.
- Blocking 5‑HT4 receptors (but not 5‑HT3) lowers spontaneous phase‑III‑like contractions in the jejunum, showing serotonin’s role in intestinal motility.
- During intestinal phase‑III‑like contractions, the lumen’s serotonin concentration rises significantly compared to low‑activity phases.
Practical Outcomes
- For biohackers using GHRP‑6, the data suggest the peptide may boost stomach motility and appetite by enhancing ghrelin signaling. While the study doesn’t give dosing guidance, it highlights potential GI side‑effects (e.g., stronger stomach contractions) to watch for when using ghrelin‑mimicking peptides.
Summary
The study shows that the hormone ghrelin (which GHRP‑6 mimics) helps trigger strong stomach contractions between meals, while serotonin (5‑HT) does the same in the small intestine. Blocking ghrelin stops these stomach movements, and blocking a specific serotonin receptor stops intestinal movements.
Abstract
Endogenous ghrelin causes interdigestive contractions of the stomach in rats. In contrast, previous studies showed that 5-HT(3) and 5-HT(4) receptors were involved in regulating intestinal interdigestive contractions. We studied the possible role of endogenous ghrelin and 5-HT regulating interdigestive gastrointestinal (GI) contractions in rats. Four strain gauge transducers were implanted on the antrum, duodenum, and proximal and distal jejunum. After an overnight fast, GI contractions were recorded in freely moving conscious rats and ghrelin receptor antagonists [(d-lys3)GHRP6; 1 micromol/kg], 5-HT(3) antagonists (Ondansetron; 0.5 mg/kg) and 5-HT(4) antagonists (GR 125,487; 1 mg/kg) were administered (bolus iv). To evaluate the relationship between the luminal concentrations of 5-HT and phase III-like contractions of the duodenum, duodenal juice was collected via the intraduodenal catheter. 5-HT content of the duodenal juice was measured by HPLC. (d-lys3)GHRP6 significantly attenuated the occurrence and amplitude of phase III-like contractions of the antrum, but not the duodenum and jejunum. 5-HT(4) antagonists significantly reduced spontaneous phase III-like contractions of the jejunum, without affecting those of the antrum and duodenum. In contrast, 5-HT(3) antagonists did not affect phase III-like contractions in GI tract. Luminal concentration of 5-HT at the phase III-like contraction (36.0 +/- 13.3 ng/ml, n = 9) was significantly higher than that at the phase I-like contractions of the duodenum (4.9 +/- 1.6 ng/ml, n = 9, P < 0.05). It is suggested that released ghrelin from the gastric mucosa mediates gastric phase III-like contractions, whereas 5-HT released from enterochromaffin cells of the duodenal mucosa mediates intestinal phase III-like contractions via 5-HT(4) receptors.
Study Information
pubmed
2008
2008-06-19T00:00:00.000Z
10.1152/ajpgi.90260.2008
34
67