EXOGENOUS MOTILIN STIMULATES ENDOGENOUS RELEASE OF MOTILIN THROUGH CHOLINERGIC MUSCARINIC PATHWAYS IN THE DOG

Background & Aims: Exogenous motilin is believed to stimulate endogeno us release of motilin, but this has not been studied in detail. The ai m of this study was to investigate whether and by what mechanism exoge nous motilin stimulates endogenous release of motilin in the dog, Meth ods: Gastric and duodenal contractile activity in conscious dogs was m onitored by chronically implanted force transducers. Plasma canine mot ilin (c-motilin) concentrations in response to exogenous porcine motil in (p-motilin) were determined by specific radioimmunoassay for c-moti lin. The release of motilin from motilin cells obtained from canine du odenal 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 mo tilin-induced motilin release was inhibited by atropine, hexamethonium , and a 5-hydroxytryptamine 3 receptor antagonist, Conclusions: in the dog, exogenous motilin stimulates endogenous motilin release through muscarinic receptors on motilin-producing cells via preganglionic path ways involving 5-hydroxytryptamine 3 receptors.