Regulation of the release of cholecystokinin by bile salts in dogs and humans

The objective of these studies was to investigate the role of bile salts in the regulation of release of cholecystokinin in response to nutrients in dogs and humans. In dogs, the intraduodenal administration of a bile salt sequestrant, cholestyramine (2, 4, or 8 g/h), resulted in a dose-related enhancement of the release of cholecystokinin- 33 39 and pancreatic protein secretion in response to intraduodenal administration of amino acids. Intraduodenal administration of cholestyramine alone did not affect basal levels of cholecystokinin- 33 39 or pancreatic protein secretion. Total diversion of bile also significantly increased the release of cholecystokinin and pancreatic protein secretion in response to intraduodenal administration of amino acids. Replacement of the bile salt pool by intraduodenal administration of taurocholate completely reversed the enhancement effect of both cholestyramine and bile diversion. In humans, oral ingestion of cholestyramine (12 g) significantly increased the release of cholecystokinin- 33 39 and gallbladder contraction in response to the oral ingestion of either a triglyceride or amino acids. These results support a physiologic role of bile salts in the negative feedback regulation of release of cholecystokinin in response to luminal nutrients.