Transport of the glutathione conjugate of ethacrynic acid by the human multidrug resistance protein MRP

FEBS Letters

Cnubben, Nicole H.P.¹  van Bladeren, Peter J.¹  Evers, Raymond²  Zaman, Guido J.R.²  Borst, Piet² 

[1] Toxicology Division, TNO Nutrition and Food Research Institute, P.O. Box 360, 3700 AJ Zeist, The Netherlands;Division of Molecular Biology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands

关键词: Multidrug resistance;    Glutathione S-transferase;    Alkylating drug;    Ethacrynic acid;   

DOI  :  10.1016/0014-5793(96)00718-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The multidrug resistance protein MRP has been shown to mediate the transport of glutathione S-conjugates across membranes. In this study we demonstrate that the glutathione S-conjugate of the diuretic drug ethacrynic acid, which is an efficient inhibitor of glutathione S-transferases, is a high-affinity substrate and inhibitor of the glutathione S-transferase activity, but also pump associated with MRP. This implies that ethacrynic acid may modulate drug resistance of tumor cells not only by inhibiting glutathione S-transferase activity, but also by inhibiting the export of drug conjugates from the cell by MRP.

【 授权许可】

Unknown