The effect of cholecystokinin-receptor antagonists on cholecystokinin-stimulated bile flow in dogs.

Cholecystokinin is a choleretic in dogs. Some of the effects of cholecystokinin in stimulating bile flow in dogs are produced by cholecystokinin stimulating the release of other choleretic hormones such as insulin and glucagon. The purpose of this study was to determine the effects of cholecystokinin receptor antagonists on canine hepatic bile flow and insulin and glucagon release from the pancreas. Cholecystokinin octapeptide (CCK-8) and intraduodenal fat were administered to dogs that had undergone cholecystectomy with chronic biliary fistulas with and without the administration of cholecystokinin receptor antagonists. Bile secretion and systemic venous insulin, glucagon, and cholecystokinin levels were measured. The cholecystokinin receptor antagonists benzotript and CR 1409 had no effect on bile flow or hormone levels when administered without cholecystokinin, whereas proglumide produced a large increase in bile flow without altering hormone levels. The response produced by proglumide may be the result of an osmotic effect produced by the substance being secreted in bile and its stimulating bile salt secretion in bile. CCK-8 and intraduodenal fat increased bile flow, bile chloride secretion, and cholecystokinin, insulin, and glucagon concentrations in venous blood. The cholecystokinin receptor antagonists benzotript and CR 1409 significantly decreased the bile flow and insulin and glucagon changes produced by exogenous CCK-8. The effect of intraduodenal fat on bile flow was not inhibited by the cholecystokinin receptor antagonists, whereas the increased insulin and glucagon levels were decreased significantly. Intraduodenal fat may release other choleretic hormones not affected by cholecystokinin receptor antagonists. The choleresis produced by exogenous CCK-8 is inhibited by cholecystokinin receptor antagonists, perhaps by inhibiting the release of the choleretic hormones insulin and glucagon.