Transport of the glutathione conjugate of ethacrynic acid by the human multidrug resistance protein MRP
article
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.
Chemicals/CAS: Adenosine Monophosphate, 61-19-8; ATP-Binding Cassette Transporters; Ethacrynic Acid, 58-54-8; Glutathione, 70-18-8; Multidrug Resistance-Associated Proteins; Recombinant Proteins; Sulfinpyrazone, 57-96-5
Chemicals/CAS: Adenosine Monophosphate, 61-19-8; ATP-Binding Cassette Transporters; Ethacrynic Acid, 58-54-8; Glutathione, 70-18-8; Multidrug Resistance-Associated Proteins; Recombinant Proteins; Sulfinpyrazone, 57-96-5
Topics
Adenosine MonophosphateATP-Binding Cassette TransportersBiological TransportCarcinoma, Non-Small-Cell LungCell MembraneDrug Resistance, MultipleEthacrynic AcidGlutathioneHumansKineticsLung NeoplasmsMultidrug Resistance-Associated ProteinsRecombinant ProteinsSaccharomyces cerevisiaeSulfinpyrazoneTransfectionTumor Cells, Cultured
TNO Identifier
38407
ISSN
00145793
Source
FEBS Letters, 391(1-2), pp. 126-130.
Pages
126-130