Secretory actions of vasoactive intestinal polypeptide, peptide histidine isoleucine and helodermin in rat small intestine: the effects of putative VIP antagonists upon VIP-induced ion secretion.
Cox. H M HM; Cuthbert. A W AW
Key Findings
- VIP, PHI, and helodermin all trigger ion secretion in rat jejunum with similar potency (EC50 ~12‑100 nM).
- Cross‑desensitisation shows these peptides probably share the same receptor.
- Four putative VIP antagonists (including two GRF peptides) showed no intrinsic activity and were not competitive antagonists; only weak inhibition was seen with two of them.
Practical Outcomes
- For biohackers, these GRF‑derived peptides should not be used as VIP blockers for gut or metabolic effects, as they lack antagonistic activity in this model. The study provides no actionable dosing or protocol guidance for humans.
Summary
In rats, three gut peptides (VIP, PHI, helodermin) cause the intestine to release ions, and they likely work through the same receptor. Scientists tried two growth‑hormone‑releasing‑factor (GRF) peptides and two other compounds to block VIP, but none acted as true blockers, so they aren't useful as selective VIP antagonists in this tissue.
Abstract
Vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), and helodermin stimulate electrogenic anion secretion in preparations of rat jejunum stripped of muscularis propria. Concentration-response curves to exogenously applied peptides yielded EC50 values of 12 nM, 12 nM and 100 nM for VIP, PHI and helodermin respectively. These secretory responses were most probably mediated via the same receptor population given that cross-desensitisation was observed between all 3 analogues. Four putative VIP antagonists, namely, two growth hormone releasing factors (GRF); [AcTyr1, D-Phe2]GRF-(1-29)-NH2 and [AcTyr1]hGRF-(1-40)-OH as well as [4Cl-D-Phe6,Leu17]VIP and VIP-(10-28) were tested for their ability to inhibit VIP induced electrogenic ion secretion. None of the above exhibited any intrinsic agonist activity nor were they competitive antagonists, although some inhibition was observed with [AcTyr1]hGRF-(1-40)-OH and VIP-(10-28). Their use as selective VIP antagonists is therefore limited in rat jejunal mucosa.
Study Information
pubmed
1989
1989-09-01T00:00:00.000Z
10.1016/0167-0115(89)90004-9
30
26