Bile salt-dependent inhibition of gallbladder emptying

Little is known about the inhibitory controls of gallbladder emptying. Since cholestyramine, a binding agent that reduces luminal concentration of bile salt, has been reported to accelerate gallbladder emptying, suggesting that bile salt is inhibitory, we hypothesized that fat-stimulated gallbladder emptying is inhibited by a bile salt-dependent mechanism. To test this idea, we compared gallbladder emptying in 10 dogs equipped with duodenal and jejunal fistulas that allowed for complete diversion of the native bile while varying concentrations of bile salt were perfused into the small intestine. In six dogs, 30 mM oleate and 5, 10, or 20 mM sodium taurocholate was perfused into the whole intestine. Since bile salt availability alters fat absorption, in a separate experiment in seven dogs we also compared gallbladder emptying while 30 mM oleate and 5 mM taurocholate were perfused between fistula and 0, 5, 10, or 20 mM taurocholate were perfused beyond jejunal fistula to separate fat from varying concentrations of bile salt. We found that intestinal taurocholate inhibited fat-stimulated gallbladder emptying in a dose-dependent fashion (P < 0.01; analysis of variance, significant linear dose effect) and that the inhibitory effect of bile salt persisted when 5-20 mM taurocholate was perfused beyond the jejunal fistula (0 vs. average of 5-20 mM taurocholate, P < 0.05, paired t-test). We conclude that fat-stimulated gallbladder emptying is inhibited by a bile salt-dependent inhibitory mechanism.