The entire vasoactive intestinal polypeptide molecule is required for the activation of the vasoactive intestinal polypeptide receptor: functional and binding studies on opossum internal anal sphincter smooth muscle.
Chakder. S S; Rattan. S S
Key Findings
- Full‑length VIP is the most potent at lowering tension in opossum internal anal sphincter smooth muscle.
- VIP fragments (VIP 2‑28, VIP 10‑28) and a GRF‑1‑29 analog can bind the VIP receptor (inhibit radiolabeled VIP binding) but have little effect on muscle relaxation.
- The potency order for receptor binding is VIP > VIP analog > VIP 10‑28 = VIP 2‑28 > GRF analog > peptide histidine isoleucine.
- IC50 values range from ~10 nM for VIP to ~10 µM for the GRF analog, indicating weaker binding for the GRF fragment.
Practical Outcomes
- For biohackers, this research suggests that taking GRF‑1‑29 (or similar fragments) is unlikely to influence gut smooth‑muscle function or provide the same effects as full VIP. It does not offer new dosing guidance or a novel benefit for longevity, metabolism, or performance, and the findings are mostly of academic interest.
Summary
The study shows that the full vasoactive intestinal peptide (VIP) molecule is needed to relax gut smooth muscle, while shorter pieces and a growth‑hormone‑releasing‑factor (GRF) analog can stick to the VIP receptor but do not really relax the muscle.
Abstract
Because no significant information exists regarding the structure-activity of vasoactive intestinal polypeptide (VIP) to gut smooth muscle, we performed functional studies in vitro on opossum internal anal sphincter (IAS) smooth muscle strips and supplemented them with binding studies to assess the ability of VIP, its fragments and analogs to inhibit [125I]VIP binding to IAS smooth muscle membranes. Binding of radiolabeled VIP to its receptor was specific, saturable and time- and temperature-dependent. Of all the substances tested, VIP was the most potent in causing a fall in the resting tension of the IAS and inhibiting [125I]VIP binding. VIP 2-28, VIP 10-28 and the putative VIP antagonists (1 x 10(-6) M) [4Cl-D-Phe6,Leu17]VIP (VIP analog) and (N-Ac-Tyr1, D-Phe2)-growth hormone-releasing factor [GRF] (1-29)-NH2 (GRF analog) caused significant inhibition of [125I]VIP binding, but had only minimal effect on the resting tension of the IAS. VIP 9-18 and VIP 1-12 had neither any significant effect nor inhibition of receptor binding. The rank order of potencies for inhibition of binding was VIP > VIP analog > VIP 10-28 = VIP 2-28 > GRF analog > peptide histidine isoleucine > VIP 9-18. The IC50 values for VIP, VIP analog, VIP 10-28, VIP 2-28, GRF analog and peptide histidine isoleucine were 9.6 x 10(-9), 1.6 x 10(-7), 5.5 x 10(-7), 6.2 x 10(-7), 1.2 x 10(-6) and 1.2 x 10(-5) M, respectively. the full action of VIP is critically dependent upon the integrity of the entire VIP molecule.(ABSTRACT TRUNCATED AT 250 WORDS)
Study Information
pubmed
1993