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 secr etion from bile acid secretion (uncoupling). As bile lipids originate from liver microsomes and are transported by carrier proteins and/or transcytoti c vesicles, such a reduction of biliary lipid secretion may lead to cytosol ic accumulation of vesicles. This study investigated whether bilirubin conj ugate, a physiologically important organic anion, caused uncoupling and whe ther hepatic retention of compounds carried by transcytotic vesicles occurr ed subsequently, using bilirubin ditaurate, a synthetic commercially availa ble compound. Methods: Cannulation of the bile duct and femoral vein was done in male Spr ague-Dawley rats. Sodium taurocholate was infused intravenously at a consta nt 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 lipid, total protein and immunoglobulin A. Results: Biliary bile acid secretion was not changed significantly by infus ion of bilirubin ditaurate in contrast, the secretion of cholesterol, phosp holipids and immunoglobulin A was decreased by 57.3, 48.7 and 44.8%, respec tively The biliary cholesterol:phospholipid ratio was increased by 19%. Unc oupling was caused by bilirubin ditaurate and biliary immunoglobulin A secr etion was decreased. Conclusions: As immunoglobulin A is a major protein carried by intrahepatic transcytotic vesicles, uncoupling may involve impairment of intrahepatic v esicular transport. Also, a reduction of immunoglobulin A secretion into bi le by organic anion-induced uncoupling may weaken biliary immunity. (C) 199 9 Blackwell Science Asia Pty Ltd.