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

FEBS Letters

Broxterman, H.J.¹  Pinedo, H.M.¹  Feller, N.¹  Währer, D.C.R.¹ 

[1] Department of Medical Oncology, BR 232, Free University Hospital, PO Box 7057, 1007 MB Amsterdam, The Netherlands

关键词: Multidrug resistance protein;    P-glycoprotein;    Calcein;    Glutathione;    BSO;    DL-buthionine (S;    R)-sulfoximine;    calcein-AM;    calcein acetoxy-methyl ester;    DNR;    daunorubicin;    GSH;    glutathione;    GS-X pump;    GSH-S-conjugate export carrier;    LTC4;    leukotriene C4;    MDR;    multidrug resistance;    MOAT;    multispecific organic anion transporter;    MRP;    multidrug resistance protein;    Pgp;    P-glycoprotein;    VCR;    vincristine;    Vp;    verapamil;   

DOI  :  10.1016/0014-5793(95)00677-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown