FUNCTIONAL EXPRESSION OF THE RAT-LIVER CANALICULAR ISOFORM OF THE MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN

The rat hepatocanalicular isoform (called mrp2) of the human multidrug resistance-associated protein (MRP) has been cloned and transiently e xpressed in COS-7 cells and in Xenopus laevis oocytes. In both systems mrp2 expression induced a markedly increased efflux of intracellularl y formed [C-14]2,4- dinitrophenyl-S-glutathione. Injection of mrp2 cRN A into oocytes also stimulated efflux of [H-3(N)]leukotriene C4. Furth ermore, mrp2 mRNA was markedly decreased in the liver of the transport mutant TR(-) rat, which has a congenital defect in the biliary excret ion of glutathione-S conjugates and of other divalent organic anions, The study provides a direct demonstration of mrp2-mediated transport f unction and supports the concept that mrp2 represents the canalicular multispecific organic anion transporter (cMOAT) of mammalian liver. (C ) 1997 Federation of European Biochemical Societies.