ATP-dependent efflux of calcein by the multidrug resistance protein (MRP): no inhibition by intracellular glutathione depletion

• Published in: FEBS letters Vol. 368; no. 2; pp. 385 - 388
• Main Authors: Feller, N., Broxterman, H.J., Währer, D.C.R., Pinedo, H.M.
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 17.07.1995
• Subjects: Adenosine Triphosphate - physiology; ATP Binding Cassette Transporter, Subfamily B, Member 1 - physiology; ATP-Binding Cassette Transporters - metabolism; Biological Transport, Active - drug effects; BSO; Buthionine Sulfoximine; Calcein; calcein acetoxy-methyl ester; calcein-AM; Cytoplasm - metabolism; daunorubicin; Daunorubicin - metabolism; DL-buthionine (S,R)-sulfoximine; DNR; Fluoresceins - metabolism; Glutathione; Glutathione - physiology; GS-X pump; GSH; GSH-S-conjugate export carrier; Humans; Indicators and Reagents - metabolism; leukotriene C4; LTC4; MDR; Methionine Sulfoximine - analogs & derivatives; Methionine Sulfoximine - pharmacology; MOAT; MRP; multidrug resistance; Multidrug resistance protein; Multidrug Resistance-Associated Proteins; multispecific organic anion transporter; Neoplasm Proteins - metabolism; P-glycoprotein; Pgp; Probenecid - pharmacology; Tumor Cells, Cultured; VCR; verapamil; vincristine; VCR; GS-X pump; DNR; MRP; P-glycoprotein; MOAT; calcein-AM; Multidrug resistance protein; Pgp; LTC 4; MDR; Vp; Calcein; GSH; Glutathione; BSO
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(95)00677-2

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.