DCCD (N, N′-Dicyclohexylcarbodiimide) Inhibits Biliary Secretion of HCO₃

Abstract

To study whether a proton pump is an integral part of the mechanism responsible for secretin-dependent biliary secretion of HCO₃ ions, the proton pump inhibitor N, N-dicyclohexylcarbodiimide (DCCD) was systemically administered to six anesthetized, secretin-infused pigs. Because biliary HCO₃ secretion varies with arterial pH, secretion rate was measured at several different arterial pH values, before and after DCCD (25 pmol/kg). At arterial pH 7.45, bile flow was 2.1 (1.6–2.9) ml/min, and HCO₃ secretion was 224 (157–311) μwol/min. DCCD reduced bile flow and HCO; secretion by 30% and 40%, respectively, independent of arterial pH. In contrast, bile acid secretion, 46 (41–59) μmol/min, was not changed by DCCD. The hepatic adenosine triphosphatase (ATP) level, 2.0 (1.8–2.1) μmol/g wet tissue, was not changed by DCCD. DCCD (10⁻⁴mol/l) affected neither Na, K-ATPase nor carbonic anhydrase activities in separate in vitro assay systems. The reduction in biliary HCO₃ 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 HCO₃.

Key Words:

• H⁺-ATPase
• Na, K-ATPase
• carbonic anhydrase
• proton pump
• secretin