Cholinergic control mechanisms for immunoreactive motilin release and motility in the canine duodenum

Abstract

The relationship of immunoreactive (IR) motilin release from the duodenum to duodenal motility changes was investigated in anesthetized dogs. Stimulation of 1 or both vagi at 5 or 15 Hz or field stimulation of intrinsic duodenal nerves produced significant increases in duodenal vein IR motilin concentrations and accompanying increases in duodenal motility. Only stimulation of both vagi at 15 Hz produced significant changes in peripheral venous concentrations of IR motilin. These occurred after a delay at a time when both the duodenum and the antrum were quiescent. Either hexamethonium or atropine blocked IR motilin release induced by stimulation of intrinsic or extrinsic nerves, while only atropine inhibited the release induced by intraarterial carbachol. The response stimulated by carbachol and blocked by atropine was tetrodotaxin insensitive and the msucarinic receptor involved was presumably located on a nonneural structure. The site sensitive to hexamethonium was presumably the neural pathway which terminated at the muscarinic receptor. Concomitant studies of duodenal motility responses to vagal and field stimulation suggested a conventional neural pathway with preganglionic cholinergic nerves in the vagus, postganglionic cholinergic nerves in the duodenum (activated by field stimulation) and a smooth muscle muscarinic receptor. Activation of antral motility by stimulation of the abdominal vagus or intraarterial carbachol injections to the antrum increased duodenal IR motilin release in the absence of duodenal motility. Thus, activation of the intrinsic nerves which cross the pylorous initiated IR motilin release and inhibited duodenal motility. Aside from this motility-independent release, there was a close correlation between increased duodenal motility and IR motilin release. The rise in endogenous IR motilin levels associated with the passage of the activity front of the migrating motor complex through the duodenum may be initiated by the combined effects of increased vagal activity and increased gastric and duodenal motor activity.