Mechanism of Ursodeoxycholic Acid- and Canrenoate-Induced Biliary Bicarbonate Secretion and the Effect on Glucose- and Amino Acid-Induced Cholestasis

Abstract

The mechanism of ursodeoxycholic acid (UDCA)- and canrenoate-induced bicarbonate choleresis was studied before and during the administration of glucose or amino acids in anaesthetized pigs. Previous studies have shown that the canalicular secretion has, on a molar basis, a relationship among the secretion of chloride, bicarbonate, and bile acids of 0.9, 0.3, and 1, respectively. Ductular secretion is associated with the transport of 0.25 mol chloride per 1 mol bicarbonate. In control experiments UDCA was associated with a biliary secretion of about 1.3 mol chloride and 0.5 mol bicarbonate per 1 mol bile acid, and canrenoate caused the secretion of 1.2 mol chloride per 1 mol bicarbonate. Intravenous infusion of glucose or amino acids increased these relationships, and after administration of UDCA or canrenoate, these relationships were still increased by at least 70% on average when compared with the control experiments. A reduction in bile secretion after glucose or amino acid infusion is opposed by UDCA or canrenoate. The effect of UDCA or canrenoate on bile secretion is not disturbed by glucose or amino acids. Both substances stimulate canalicular bicarbonate secretion and could be of importance in improving cholestatic conditions.

Key Words:

• Bile acids
• bile flow
• canaliculi
• chloride
• ductuli
• Na/H exchange
• proton pump