Vasoactive intestinal polypeptides induce guinea-pig ileum contraction by causing release of endogenous acetylcholine

Two vasoactive intestinal polypeptide (VIP) analogues were observed to induce a concentration-dependent contraction of guinea-pig ileum, which was blocked by atropine but not by tubocurarine. The analogue from guinea-pig, VIP [VIP(gp)], was the most potent inducer of ileum contraction, followed by human-porcine-rat VIP [VIP(hpr)], which differs from VIP(gp) by 4 nonpolar amino acid substitutions. VIP(1-15), composed of only the first 15 of the 28 amino acids of VIP(hpr), was without effect. The relative potency of VIP(gp), VIP(hpr), and acetylcholine was 50 to 100 times more potent in inducing contraction in ileums of which the acetylcholinesterase was inactivated by paraoxon than in the controls. The VIP analogues which induced contraction of ileum also induced secretion of endogenous acetylcholine. The secreted acetylcholine was quantified by high-performance liquid chromatography using electrochemical detection and an immobilized-enzyme column consisting of choline oxidase and acetylcholinesterase. The induction of ileum contraction by VIP(gp), from 10nM to 1 microM VIP, was correlated with the amounts of ACh secreted from ileum. VIP(hpr) induced less acetylcholine secretion than VIP(gp), and was also less potent in causing ileum contraction. VIP(1-15), even at 10 microM, caused neither acetylcholine release nor ileum contraction.