Motilin regulates interdigestive gastric blood flow in dogs

Background & Aims: Gastric blood flow exhibits cyclical increases in phase with the interdigestive contractions and secretion of the stomach in dogs. The aim of this study is to clarify the regulatory role of motilin in interdigestive gastric blood flow in dogs. Methods: Blood flow of the left gastric (LGA) and superior mesenteric (SMA) arteries were measured by ultrasound transit-time blood-flow meters in 5 conscious dogs. Motilin was infused intravenously with or without Phe-cyclo[Lys-Tyr(3-tBu)-betaAla-] . trifluoroacetate (GM-109; motilin antagonist), granisetron (5-HT3 antagonist), atropine, hexamethonium (C6), phenoxybenzamine, propranolol, or cimetidine. Results: Motilin (12.5, 25, 50, and 100 pmol . kg(-1) . h(-1)) induced LGA blood-flow responses, consisting of a sustained increase and a rapid phasic change coupled with a contraction, without affecting the blood pressure, heart rate, and SMA blood flow. GM-109 completely abolished the LGA, motility, and secretory responses to motilin (100 pmol . kg(-1) . h(-1)). Atropine abolished motilin-induced gastric contractions, secretion, and phasic changes of LGA blood flow but failed to affect the sustained flow increase. However, atropine partially inhibited the LGA responses to lower doses of motilin. The LGA flow responses to motilin were not inhibited by granisetron, C6, alpha-adrenergic, beta-adrenergic, or H-2 blockers. Motilin induced significantly larger gastric vasodilatation than the equivalent doses of VIP. Conclusions: Motilin has a potent and selective gastric vasodilator effect, which appears to be mediated by both cholinergic and noncholinergic mechanisms. Motilin plays an important role in the regulation of interdigestive gastric blood flow in dogs.