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) transports calcein from the cytoplasmic compartment of tumor cells, in contrast to P-glycoprotein which transports calcein acetoxymethyl ester from the plasmamembrane. The transport of calcein by MRP is ATP-dependent and is inhibited by probenecid and vincristine. Intracellular glutathione (GSH) depletion which occurred when cells were exposed to buthionine sulfoximine had no effect on the efflux of calcein, whereas it reversed the daunorubicin accumulation deficit in MRP overexpressing tumor cells. In conclusion, ATP-dependent transport of calcein and possibly other organic anions by MRP is not inhibited by a large decrease of the intracellular GSH concentration, that inhibits daunorubicin efflux by MRP.
Feller
N
N
Department of Medical Oncology, Free University Hospital, Amsterdam, The Netherlands.
Broxterman
H J
HJ
Währer
D C
DC
Pinedo
H M
HM
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000502:physiology*; D001693:Biological Transport, Active / Q000187:drug effects; D019328:Buthionine Sulfoximine; D003593:Cytoplasm / Q000378:metabolism; D003630:Daunorubicin / Q000378:metabolism; D005452:Fluoresceins / Q000378:metabolism*; D005978:Glutathione / Q000502:physiology*; D006801:Humans; D007202:Indicators and Reagents / Q000378:metabolism*; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins / Q000378:metabolism*; D011339:Probenecid / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D000255:Adenosine Triphosphate; D019328:Buthionine Sulfoximine; D003630:Daunorubicin; D005452:Fluoresceins; D005978:Glutathione; D007202:Indicators and Reagents; D008717:Methionine Sulfoximine; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D011339:Probenecid; C085925:calcein AM; C007740:fluorexon