Title
Transport of the glutathione conjugate of ethacrynic acid by the human multidrug resistance protein MRP
Author
Zaman, G.J.R.
Cnubben, N.H.P.
van Bladeren, P.J.
Evers, R.
Borst, P.
Instituut CIVO-Toxicologie en Voeding TNO
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 (1-2), 126-130
Document type
article