DCCD (N,N'-dicyclohexylcarbodiimide) inhibits biliary secretion of HCO-3.
To study whether a proton pump is an integral part of the mechanism responsible for secretin-dependent biliary secretion of HCO-3 ions, the proton pump inhibitor N,N'-dicyclohexylcarbodiimide (DCCD) was systemically administered to six anesthetized, secretin-infused pigs. Because biliary HCO-3 secretion varies with arterial pH, secretion rate was measured at several different arterial pH values, before and after DCCD (25 mumol/kg). At arterial pH 7.45, bile flow was 2.1 (1.6-2.9) ml/min, and HCO-3 secretion was 224 (157-311) mumol/min. DCCD reduced bile flow and HCO-3 secretion by 30% and 40%, respectively, independent of arterial pH. In contrast, bile acid secretion, 46 (41-59) mumol/min, was not changed by DCCD. The hepatic adenosine triphosphatase (ATP) level, 2.0 (1.8-2.1) mumol/g wet tissue, was not changed by DCCD. DCCD (10(-4) mol/l) affected neither Na,K-ATPase nor carbonic anhydrase activities in separate in vitro assay systems. The reduction in biliary HCO-3 secretion induced by the proton pump inhibitor DCCD may indicate that a proton pump is integrated into the mechanism responsible for secretin-dependent biliary secretion of HCO-3.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism; D001652:Bile Ducts / Q000378:metabolism*; D002234:Carbodiimides / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism; D004024:Dicyclohexylcarbodiimide / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D008099:Liver / Q000378:metabolism; D011522:Protons; D012636:Secretory Rate / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013552:Swine
D001639:Bicarbonates; D001647:Bile Acids and Salts; D002234:Carbodiimides; D011522:Protons; D004024:Dicyclohexylcarbodiimide; D000255:Adenosine Triphosphate; D002256:Carbonic Anhydrases; D000254:Sodium-Potassium-Exchanging ATPase