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Role of multidrug resistance protein (MRP) in glutathione S-conjugate transport in mammalian cells.

The human multidrug resistance protein (MRP), a 190-kDa member of the ABC-protein superfamily, is an ATP-dependent glutathione S-conjugate carrier (GS-X pump) and is present in membranes of many, if not all, cells. Overexpression of MRP in tumor cells contributes to resistance to natural product drugs and oxyanions. The function and specificity of the GS-X pump MRP is very similar to the canalicular multispecific organic union carrier (cMOAT) present in the canalicular membrane domain of hepatocytes and functioning in primary-active excretion of multivalent anionic conjugates into bile. In this review we discuss the function of MRP as GS-X pump in mammalian cells, its putative role in multidrug resistance, its relation to the hepatocyte cMOAT system and its dysfunction in the mutant TR- Wistar rat.