Title
Transport of the glutathione conjugate of ethacrynic acid by the human multidrug resistance protein MRP
Author
Instituut CIVO-Toxicologie en Voeding TNO
Zaman, G.J.R.
Cnubben, N.H.P.
van Bladeren, P.J.
Evers, R.
Borst, P.
Publication year
1996
Abstract
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
Subject
Adenosine Monophosphate
ATP-Binding Cassette Transporters
Biological Transport
Carcinoma, Non-Small-Cell Lung
Cell Membrane
Drug Resistance, Multiple
Ethacrynic Acid
Glutathione
Humans
Kinetics
Lung Neoplasms
Multidrug Resistance-Associated Proteins
Recombinant Proteins
Saccharomyces cerevisiae
Sulfinpyrazone
Transfection
Tumor Cells, Cultured
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DOI
https://doi.org/10.1016/0014-5793(96)00718-1
TNO identifier
38407
ISSN
0014-5793
Source
FEBS Letters, 391 (391), 126-130
Document type
article