Effect of acid-base balance and acetazolamide on ursodeoxycholate-induced biliary bicarbonate secretion

Biliary bicarbonate secretion may play an important role in canalicular bile flow. The aim of this study was to examine the effect of disturbances in acid-base balance on ursodeoxycholate (UDCA)-induced choleresis and bicarbonate secretion. Isolated rat livers were perfused with an erythrocyte-free solution in a recirculating system. In the absence of bile acid infusion, bicarbonate concentration in bile varied in parallel with that in the perfusate (15.6-35.1 mM), irrespective of the perfusate pH (7.26-7.55). Bicarbonate concentration in bile was not significantly different from that in the perfusate. Under UDCA infusion (2 mumol/min), bicarbonate concentration in bile and perfusate was correlated (P less than 0.001). Bicarbonate concentration in bile was always higher than that in the perfusate. Perfusate pH changes (7.25-7.56) induced by changes in perfusate carbon dioxide tension had no significant effect on bicarbonate secretion or bile flow. A significant correlation was found between bile flow and bicarbonate secretion both with and without UDCA. Acetazolamide (1 mM) significantly decreased both UDCA-stimulated bile flow (-27.7%) and bicarbonate concentration (-51.8%). These results suggest that canalicular bicarbonate secretion includes an equilibrative component that is possibly linked to diffusion of plasmatic CO2 or HCO3- and a concentrative transport that is stimulated by UDCA, is independent of plasma pH, and involves carbonic anhydrase.