EFFECT OF BILE-SALT BINDING OR PROTEASE INACTIVATION ON PLASMA CHOLECYSTOKININ AND GALLBLADDER RESPONSES TO BOMBESIN

Background/Aims: Bombesin-stimulated plasma cholecystokinin levels dec rease after an initial increase despite continuous infusion of bombesi n. The aim of this study was to determine if a feedback mechanism, med iated by bile salts or proteolytic enzymes, is responsible for this de cline. Methods: Bombesin (1.0 ng.kg(-1).min(-1)) was infused into volu nteers for 180 minutes on separate occasions. Cholestyramine, colestip ol, camostate, or saline were perfused intraduodenally during the seco nd hour of the tests. Cholestyramine was also administered without inf usion of bombesin. Results: Colestipol and cholestyramine, dependent o n their bile salt-binding capacity, markedly enhanced (P < 0.05) bombe sin-stimulated plasma cholecystokinin from 2.1 +/- 0.5 pmol/L to 6.4 /- 2.2 pmol/L and 12.1 +/- 3.3 pmol/L (P < 0.05 vs. colestipol), respe ctively, and further decreased gallbladder volume (P < 0.05) from 9.4 +/- 1.6 mt to 2.0 +/- 0.4 mL and 2.2 +/- 0.5 mL, respectively. The pro tease inhibitor camostate had no effect. Bile salt precipitation also enhanced plasma pancreatic polypeptide responses (P < 0.01) but did no t alter gastrin responses. Plasma cholecystokinin responses to cholest yramine without bombesin infusion varied considerably, but increments were highly correlated to decreases in gallbladder volume (r = 0.91; P < 0.005). Conclusions: Bile salt sequestration but not protease inact ivation enhances plasma cholecystokinin and gallbladder responses to b ombesin infusion in humans.