TRANSPORT OF THE GLUTATHIONE CONJUGATE OF ETHACRYNIC-ACID BY THE HUMAN MULTIDRUG-RESISTANCE PROTEIN MRP

The multidrug resistance protein MRP has been shown to mediate the tra nsport of glutathione S-conjugates across membranes, In this study me demonstrate that the glutathione S-conjugate of the diuretic drug etha crynic acid, which is an efficient inhibitor of glutathione S-transfer ases, 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 glu tathione S-transferase activity, but also by inhibiting the export of drug conjugates from the cell by MRP.