Biliary excretion of tauroursodeoxycholate-3-sulfate in the rat

Biliary organic anion excretion is mediated by an ATP-dependent primary act ive transporter, multidrug resistance protein 2. On the other hand, a multi plicity of canalicular organic anion transport has been suggested. Ursodeox ycholic acid, the 7 beta -epimer of chenodeoxycholic acid, is clinically us ed for various hepatobiliary diseases. In our previous study, the contribut ion of multidrug resistance protein 2 for biliary excretion of taurine-conj ugated bile acid sulfates depended on the numbers of hydroxyl residue. Ther efore, to further examine the effect of hydrophobicity on the substrate spe cificity of multidrug resistance protein 2, we examined the effect of bile acid conjugates and organic anions on biliary excretion of tauroursodeoxych olate-3-sulfate, taurine and sulfonate-conjugated ursodeoxycholic acid, in rats. Biliary tauroursodeoxycholate-3-sulfate excretions was markedly delay ed in Eisai hyperbilirubinemic rats. Taurolithocholate-3-sulfate inhibited but ursodeoxycholate-3,7-disulfate did not affect biliary tauroursodeoxycho late-3-sulfate excretion. Biliary tauroursodeoxycholate-3-sulfate excretion was inhibited by sulfobromophthalein, but was not inhibited by dibromosulf ophthalein and cefpiramide. These findings indicate that tauroursodeoxychol ate-3-sulfate is very specific for multidrug resistance protein 2. (C) 2001 Elsevier Science Inc. All rights reserved.