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.
Kajihara
T
T
First Department of Internal Medicine, Hiroshima University School of Medicine, Japan.
Tazuma
S
S
Yamashita
G
G
Kajiyama
G
G
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D001659:Biliary Tract / Q000187:drug effects* / Q000378:metabolism*; D001663:Bilirubin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D050356:Lipid Metabolism; D008297:Male; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013654:Taurine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
D001647:Bile Acids and Salts; D011506:Proteins; D013654:Taurine; C054146:bilirubin ditaurine; D001663:Bilirubin