MECHANISM OF MOTILIN-INDUCED CONTRACTIONS IN ISOLATED-PERFUSED CANINE STOMACH

Background: Motilin is known to induce gastric phase III contractions via neural pathways in vivo, but the local mechanism of action is not clearly determined. Methods: An isolated perfused canine stomach was used to demonstrate the mechanism of motilin. Synthetic canine motilin at doses of 0.1, 0.3, 1.0, and 3.0 μg/h was infused intra-arterially, and effects of several receptor antagonists on motilin-induced contractions were examined. Results: The immunoreactive motilin concentration of venous effluent showed that motilin at doses of 0.1 and 0.3 μg/h was within the physiological range. Each dose of motilin induced phasic contractions in the isolated stomach, and a dose-related increase in frequency was observed, but not their mean amplitude. Atropine, hexamethonium, ICS205-930, BRL43694, phentolamine, yohimbine, and propranolol significantly inhibited motilin-induced contractions. Naloxone, methysergide, and timolol did not affect the response of motilin. Prazosin significantly increased the mean amplitude of motilin-induced contractions. Conclusions: Physiological dose of motilin can initiate phasic contractions in the stomach independently of the presence of the extrinsic nerves. The results suggest that cholinergic pathway, 5-hydroxytryptamine (HT)3 receptors, and α receptors are involved in the motilin-induced contractions. © 1992.