ATP-DEPENDENT EFFLUX OF CALCEIN BY THE MULTIDRUG-RESISTANCE PROTEIN (MRP) - NO INHIBITION BY INTRACELLULAR GLUTATHIONE DEPLETION

In this study we report that the multidrug resistance protein (MRP) tr ansports calcein from the cytoplasmic compartment of tumor cells, in c ontrast to P-glycoprotein which transports calcein acetoxymethyl ester from the plasmamembrane. The transport of calcein by MRP is ATP-depen dent and is inhibited by probenecid and vincristine. Intracellular glu tathione (GSH) depletion which occurred when cells vr ere exposed to b uthionine sulfoximine had no effect on the efflux of calcein, whereas it reversed the daunorubicin accumulation deficit in MRP overexpressin g tumor cells. Tn conclusion, ATP-dependent transport of calcein and p ossibly other organic anions by MRP is not inhibited by a large decrea se of the intracellular GSH concentration, that inhibits daunorubicin efflux by MRP.