GHRP-6
Growth Hormone Releasing Peptide-6, Growth hormone-releasing hexapeptide, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2
Ghrelin acts in the brain to block colonic hyperpermeability in response to lipopolysaccharide through the vagus nerve.
Ishioh. Masatomo M; Nozu. Tsukasa T; Igarashi. Sho S; Tanabe. Hiroki H; Kumei. Shima S; Ohhira. Masumi M; Okumura. Toshikatsu T
Key Findings
- Central (brain) administration of ghrelin blocks LPS‑induced colonic hyperpermeability in a dose‑dependent manner.
- The protective effect requires an intact vagus nerve and cholinergic signaling; vagotomy or atropine removes the benefit.
- Blocking the ghrelin receptor with (D‑Lys3)-GHRP‑6 or blocking orexin‑1 receptors stops the gut‑protective effect, indicating involvement of ghrelin and orexin pathways.
Practical Outcomes
- For biohackers, the data hint that boosting central ghrelin activity—potentially via GHRP‑6 or other secretagogues—might help maintain gut barrier integrity and lower systemic inflammation. However, the study used direct brain injections in rats, so translating this to oral or sub‑cutaneous use in humans is speculative. If you experiment, consider combining GHRP‑6 with strategies that support vagal tone (e.g., deep breathing, cold exposure) and monitor gut health markers.
Summary
In rats, giving ghrelin directly into the brain stops the gut lining from becoming leaky after an inflammatory trigger (LPS). This protective effect needs the vagus nerve and orexin signaling, and it doesn't happen when ghrelin is given just into the body or when a ghrelin blocker is used.
Abstract
Brain ghrelin plays a role in gastrointestinal functions. Among them, ghrelin acts centrally to stimulate gastrointestinal motility and induce visceral antinociception. Intestinal barrier function, one of important gastrointestinal functions, is also controlled by the central nervous system. Little is, however, known about a role of central ghrelin in regulation of intestinal permeability. The present study was performed to clarify whether brain ghrelin is also involved in regulation of intestinal barrier function and its mechanism. Colonic permeability was estimated in vivo by quantifying the absorbed Evans blue in colonic tissue in rats. Intracisternal injection of ghrelin dose-dependently abolished increased colonic permeability in response to LPS while intraperitoneal injection of ghrelin at the same dose or intracisternal injection of des-acyl-ghrelin failed to block it. Carbachol potently attenuated LPS-induced intestinal hyperpermeability, and atropine or bilateral subdiaphragmatic vagotomy prevented the improvement of intestinal hyperpermeability by central ghrelin. Intracisternal (D-Lys3)-GHRP-6, a selective ghrelin receptor antagonist, significantly blocked improvement of intestinal barrier function by intravenously administered 2-deoxy-d-glucose, central vagal stimulant. Intracisternal injection of orexin 1 receptor antagonist, SB-334867 blocked intracisternal ghrelin-induced improvement of colonic hyperpermeability. These results suggest that exogenously administered or endogenously released ghrelin acts centrally to improve a disturbed intestinal barrier function through orexinergic signaling and the vagal cholinergic pathway. Central ghrelin may be involved in the pathophysiology and be a novel therapeutic option in not only gastrointestinal diseases such as irritable bowel syndrome but also non-gastrointestinal diseases associated with the altered intestinal permeability.
Study Information
pubmed
2020
2020-05-19T00:00:00.000Z
10.1016/j.neuropharm.2020.108116
22
56