Vasoactive intestinal peptide (VIP) as transmitter of inhibitory motor neurons of the gut: evidence from the use of selective VIP antagonists and VIP antiserum.
Grider. J R JR; Rivier. J R JR
Key Findings
- GRF‑1‑29 acts as a weak antagonist of VIP‑induced intestinal relaxation.
- VIP is confirmed as the main transmitter causing gut muscle relaxation in these animal models.
- The potency order for blocking VIP was: VIP10‑28 > VIP analog > GRF‑1‑29.
Practical Outcomes
- For biohackers using GRF‑1‑29 to boost growth hormone, be aware it may also dampen VIP activity, potentially affecting gut motility or digestion. This could explain occasional gastrointestinal side effects. Adjusting dosage or timing might mitigate any unwanted gut effects, but more human data are needed.
Summary
The study shows that a peptide called GRF‑1‑29, normally known for stimulating growth hormone, can also block the action of another peptide, VIP, which relaxes the gut. In lab experiments on guinea pig and rat intestines, GRF‑1‑29 reduced VIP‑driven muscle relaxation, though it was less potent than other VIP blockers.
Abstract
The role of vasoactive intestinal peptide (VIP) in neurally mediated relaxation of guinea pig and rat intestine was examined with three putative VIP antagonists: a C-terminal sequence of VIP (VIP10-28), substituted analogs of VIP ([4-Cl-D-Phe6, Leu17]VIP) and growth hormone releasing factor (GRF) ([Ac-Tyr1, D-Phe2] GRF1-29). The three agents inhibited selectively relaxation induced by VIP and its homolog, peptide histidine isoleucine. Inhibition of VIP-induced relaxation in tenia coli and gastric fundic strips was consistent with competitive antagonism. Relaxation induced by field stimulation (80 V; 1 msec; 0.1-16 Hz) which is accompanied by a stoichiometric increase in VIP release was inhibited by the three antagonists in the following order of potency: VIP10-28 greater than VIP analog greater than GRF analog. The descending relaxation component of the peristaltic reflex induced by graded stretch of the orad end of a rat colonic segment which is also accompanied by an increase in VIP release, was inhibited by the three VIP antagonists in the same order of potency: VIP10-28 greater than VIP analog greater than GRF analog. The most potent antagonist, VIP10-28, abolished descending relaxation at the lowest grades of stretch (2 and 4 g) and inhibited relaxation at the highest grades of stretch (10 g) by 79%. The results indicate that VIP (and peptide histidine isoleucine) is the transmitter responsible for neurally induced gastric and intestinal relaxation.
Study Information
pubmed
1990