Exogenous motilin stimulates endogenous release of motilin through cholinergic muscarinic pathways in the dog.

BACKGROUND & AIMS: Exogenous motilin is believed to stimulate endogenous release of motilin, but this has not been studied in detail. The aim of this study was to investigate whether and by what mechanism exogenous motilin stimulates endogenous release of motilin in the dog.

METHODS

Gastric and duodenal contractile activity in conscious dogs was monitored by chronically implanted force transducers. Plasma canine motilin (c-motilin) concentrations in response to exogenous porcine motilin (p-motilin) were determined by specific radioimmunoassay for c-motilin. The release of motilin from motilin cells obtained from canine duodenal mucosa was studied in vitro using a perifusion system.

RESULTS

In vitro, c-motilin release was stimulated by carbachol but not by p-motilin, and the carbachol-induced c-motilin release was inhibited by atropine. In vivo, exogenous p-motilin stimulated endogenous c-motilin release and gastric and duodenal phase III-like contractions; this motilin-induced motilin release was inhibited by atropine, hexamethonium, and a 5-hydroxy-tryptamine 3 receptor antagonist.

CONCLUSIONS

In the dog, exogenous motilin stimulates endogenous motilin release through muscarinic receptors on motilin-producing cells via preganglionic pathways involving 5-hydroxytryptamine 3 receptors.