Vasoactive intestinal polypeptide provokes acetylcholine release from the myenteric plexus.

Effects of vasoactive intestinal polypeptide (VIP) on the release of acetylcholine (ACh) from longitudinal muscle strips with myenteric plexus (LM) preparations were examined in the guinea pig small intestine. VIP (10(-10) to 10(-6) M) induced a concentration-dependent contraction of LM preparation. The VIP-induced contractions seem to be related to three components, the scopolamine-sensitive, the scopolamine-insensitive, the tetrodotoxin-sensitive, and the tetrodotoxin-insensitive contractions. VIP (10(-10) to 10(-6) M) induced a concentration-dependent increase in the release of [3H]ACh from LM preparations preloaded with [3H]choline. The VIP-evoked [3H]ACh release was inhibited by removal of Ca2+ from the perfusion medium and by treatment with tetrodotoxin but not by scopolamine and hexamethonium. The spontaneous and VIP-evoked [3H]ACh release was not affected by phentolamine, propranolol, methysergide, diphenhydramine, cimetidine, bicuculline, or [D-Pro2, D-Trp7,9]substance P. The result demonstrates that VIP induces contractions of longitudinal smooth muscle directly and indirectly by the stimulation of both cholinergic neurons and noncholinergic excitatory neurons.