CHOLECYSTOKININ-INDUCED CONTRACTION OF OPOSSUM SPHINCTER OF ODDI - MECHANISM OF ACTION

In this study, we evaluated the mechanism of action whereby cholecystokinin increases spike-burst rate of the opossum sphincter of Oddi (SO). Each spike burst corresponds to a peristaltic SO contraction. Two types of animal preparations were evaluated: (1) awake chronic animal preparations and (2) anesthetized animals. A total of 19 chronic animals were prepared by implantation of electrodes on the SO, gastric antrum, duodenum, and jejunum. SO spike-burst rate was stimulated by intravenous infusion of CCK-OP (10 ng/kg/min), feeding, or intraduodenal infusion of fat-containing nutrient. Each stimulus was begun 20 min after cessation of phase III duodenal MMC activity and caused an increase in SO spike-burst rate from about 2 to 6/min that lasted for 1hr. Such increases were antagonized substantially by hexamethonium, atropine, or methysergide. The CCK antagonist, L364718, antagonized the excitatory SO response to CCK-OP infusion or intraduodenal infusion of fat-containing nutrient (Isocal) but did not antagonize the response to feeding; CR1409 had no antagonistic effect on SO response to any of the three types of stimuli. In the acute studies in anesthetized animals, an intravenous bolus dose of CCK-OP (800 ng/kg) caused a substantial increase in SO spikeburst rate that was antagonized by CR1409 but not by atropine, hexamethonium, methysergide, L364718, or TTX. From these results we conclude that: (1) SO excitatory responses evoked by exogenous or endogenous CCK in awake animals are elicited by an action on cholinergic and tryptaminergic nerves with negligible direct effect on SO smooth muscle, (2) actions of bolus doses in the acute studies are evoked mainly by a direct effect of CCK-OP on SO smooth muscle, and (3) different subtypes of CCK receptors antagonized by L364718 and CR1409, respectively, exist on SO cholinergic nerves and SO smooth muscle. © 1990 Plenum Publishing Corporation.