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.
D000086:Acetazolamide / Q000494:pharmacology*; D000136:Acid-Base Equilibrium; D000138:Acidosis / Q000378:metabolism; D000471:Alkalosis / Q000378:metabolism; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D001646:Bile / Q000187:drug effects / Q000378:metabolism*; D003840:Deoxycholic Acid / Q000031:analogs & derivatives*; D004573:Electrolytes / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010101:Oxygen Consumption; D051381:Rats; D011919:Rats, Inbred Strains; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*
D001639:Bicarbonates; D004573:Electrolytes; D003840:Deoxycholic Acid; D014580:Ursodeoxycholic Acid; D000086:Acetazolamide