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FEBS Lett. 1996 Aug 5;391(1-2):126-30.

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

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Division of Molecular Biology, Netherlands Cancer Institute, Amsterdam, The Netherlands.


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-conjugate 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.

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