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

Abstract

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.