title: Effects of organic anions and bile acid conjugates on biliary excretion of LTC4 in the rat.
abstract: Biliary organic anion excretion is mediated by an ATP-dependent primary active transporter, so-called canalicular multispecific organic anion transporter (cMOAT). On the other hand, a multiplicity of canalicular organic anion transport has been suggested. Therefore, to examine the substrate specificity of cMOAT using inhibition of excretion of [3H] LTC4-derived radioactive products in the bile as a marker, we examined the effects of various organic anions and bile acid conjugates on the biliary excretion of LTC4 in rats. Biliary excretion of the metabolites of [3H] LTC4, which was injected via the femoral vein, was markedly inhibited by sulfobromophthalein-glutathione, taurolithocholate-3-sulfate, and ursodeoxycholate-3-O-glucuronide. In contrast, dibromosulfophthalein and cefpiramide slightly inhibited, and pravastatin, taurocholate, and 3,7-sul-UDC did not affect biliary LTC4 excretion. Furthermore, vinblastine and phenothiazine, a P-glycoprotein substrate and inducer, did not affect biliary LTC4 excretion. Among various organic anions and bile acid conjugates, LTC4, sulfobromophthalein-glutathione, taurolithocholate-3-sulfate, and ursodeoxycholate-3-O-glucuronide may be good substrates for cMOAT.
authors.affiliation: Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kitaura
authors.forename: H
authors.initials: H
authors.lastname: Takikawa
authors.forename: M
authors.initials: M
authors.lastname: Yamanaka
mesh_terms: D000818:Animals; D027321:Anion Transport Proteins; D001646:Bile / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000494:pharmacology*; D001659:Biliary Tract / Q000187:drug effects / Q000378:metabolism*; D001692:Biological Transport; D002352:Carrier Proteins / Q000494:pharmacology*; D006933:Hyperbilirubinemia, Hereditary / Q000378:metabolism; D017997:Leukotriene C4 / Q000378:metabolism*; D008297:Male; D010640:Phenothiazines / Q000494:pharmacology; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley
chemical_list: D027321:Anion Transport Proteins; D001647:Bile Acids and Salts; D002352:Carrier Proteins; D010640:Phenothiazines; D017997:Leukotriene C4