Effects of bilirubin ditaurate on biliary secretion of proteins and lipids: Influence on the hepatic vesicle transport system

BACKGROUND: Several organic anions cause dissociation of biliary lipid secretion from bile acid secretion (uncoupling). As bile lipids originate from liver microsomes and are transported by carrier proteins and/or transcytotic vesicles, such a reduction of biliary lipid secretion may lead to cytosolic accumulation of vesicles. This study investigated whether bilirubin conjugate, a physiologically important organic anion, caused uncoupling and whether hepatic retention of compounds carried by transcytotic vesicles occurred subsequently, using bilirubin ditaurate, a synthetic commercially available compound. METHODS: Cannulation of the bile duct and femoral vein was done in male Sprague-Dawley rats. Sodium taurocholate was infused intravenously at a constant rate of 100 nmol/min per 100 g bodyweight. Bilirubin ditaurate (50 nmol/min per 100 g bodyweight) was infused concomitantly, followed by periodical bile collection for analysis of lipids, total protein and immunoglobulin A. RESULTS: Biliary bile acid secretion was not changed significantly by infusion of bilirubin ditaurate. In contrast, the secretion of cholesterol, phospholipids and immunoglobulin A was decreased by 57.3, 48.7 and 44.8%, respectively. The biliary cholesterol:phospholipid ratio was increased by 19%. Uncoupling was caused by bilirubin ditaurate and biliary immunoglobulin A secretion was decreased. CONCLUSIONS: As immunoglobulin A is a major protein carried by intrahepatic transcytotic vesicles, uncoupling may involve impairment of intrahepatic vesicular transport. Also, a reduction of immunoglobulin A secretion into bile by organic anion-induced uncoupling may weaken biliary immunity.