Roles of endogenous cholecystokinin in biliary, pancreatic and gastric function: studies with L-364,718, a specific cholecystokinin receptor antagonist.
A new, highly potent antagonist of gut cholecystokinin (CCK) receptors has been examined for effects upon postprandial biliary and exocrine pancreatic secretion in conscious dogs with chronic duodenal pouches. This drug (L-364,718) markedly inhibited the postprandial increases in biliary volume, bile acid and bilirubin secretion. However, even at high p.o. doses relative to its ability to antagonize the effects of exogenous CCK, no effects were observed upon the pancreatic secretion of either fluid volume or amylase and lipase under similar conditions. In additional studies, pretreatment with L-364,718 did not significantly reverse the inhibitory effects of a fatty acid salt (sodium oleate) upon gastric emptying in gastric fistula dogs. Moreover, pretreatment with L-364,718 had no significant effects upon postprandial acid and pepsin secretion in lesser curvature (vagally innervated) pouch dogs or did it affect basal (interdigestive) gastric secretion in rats. These results suggest that endogenous CCK plays a critical physiological role in regulating postprandial biliary outflow, but not pancreatic enzyme secretion or the gastric emptying of at least liquid fatty substances. The latter two findings stand in contrast with classical views regarding the physiological function(s) of this hormone.
D000681:Amylases / Q000378:metabolism; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D001647:Bile Acids and Salts / Q000378:metabolism; D001659:Biliary Tract / Q000187:drug effects*; D001663:Bilirubin / Q000378:metabolism; D002766:Cholecystokinin / Q000502:physiology*; D020109:Devazepide; D005502:Food; D005746:Gastric Emptying / Q000187:drug effects; D008049:Lipase / Q000378:metabolism; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D011949:Receptors, Cholecystokinin / Q000378:metabolism*; D013270:Stomach / Q000187:drug effects*
D001570:Benzodiazepinones; D001647:Bile Acids and Salts; D011949:Receptors, Cholecystokinin; D002766:Cholecystokinin; D008049:Lipase; D000681:Amylases; D020109:Devazepide; D001663:Bilirubin