THE KAPPA-AGONIST FEDOTOZINE MODULATES COLONIC DISTENSION-INDUCED INHIBITION OF GASTRIC-MOTILITY AND EMPTYING IN DOGS

Background/Aims: Gastric motor disturbances, associated with a delay i n gastric emptying, occur in patients with the irritable bowel syndrom e. The influence of fedotozine and kappa agonists on the cologastric r eflex produced by nonpainful colonic distention was evaluated in consc ious dogs. Methods: Colonic distention was applied in dogs fitted with either strain gauges or gastric cannula to assess its influence on ga strointestinal motility and gastric emptying, respectively. Results: C olonic distention delayed the occurrence of gastric migrating motor co mplex by 141%, an effect blocked by intravenous fedotozine, U 50 488 ( 25 and 50 mu g/kg), and hexamethonium (0.5 mg/kg) but not by D-Ala(2), N-methyl, Phe(4), Gly(5)-ol enkephalin (1, 5, and 10 mu g/kg), granis etron (50 and 100 mu g/kg), or bretylium tosylate (5 mg/kg). Nor-binal torphimine hydrochloride (1 mg/kg intravenously) eliminated the suppre ssive action of fedotozine. Colonic distention reduced the 1-hour gast ric emptying of solids by 40.1%, an effect blocked by fedotozine and U 50 488 (50 and 100 mu g/kg); nor-binaltorphimine hydrochloride (1 mg/ kg) antagonized the blocking effect of fedotozine. Conclusions: Fedoto zine acts through kappa receptors to block the colonic distention-indu ced delay on gastric motility and emptying. The cologastric reflex inv olves nicotinic ganglionic receptors but not adrenergic pathway and 5- hydroxytryptamine 3 receptors.