ROLE OF MULTIDRUG-RESISTANCE PROTEIN (MRP) IN GLUTATHIONE S-CONJUGATETRANSPORT 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 c arrier (GS-X pump) and is present in membranes of many, if not all, ce lls, 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 org anic anion carrier (cMOAT) present in the canalicular membrane domain of hepatocytes and functioning in primary-active excretion of multival ent anionic conjugates into bile. In this review we discuss the functi on of MRP as GS-X pump in mammalian cells, its putative role in multid rug resistance, its relation to the hepatocyte cMOAT system and its dy sfunction in the mutant TR(-) Wistar rat. (C) European Association for the Study of the Liver.