Functional expression of the rat liver canalicular isoform of the multidrug resistance‐associated protein

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

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