leukotriene-c4 and Hyperbilirubinemia--Hereditary

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.

Topics: Animals; Anion Transport Proteins; Bile; Bile Acids and Salts; Biliary Tract; Biological Transport; Carrier Proteins; Hyperbilirubinemia, Hereditary; Leukotriene C4; Male; Phenothiazines; Rats; Rats, Mutant Strains; Rats, Sprague-Dawley