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Transport of the glutathione conjugate of ethacrynic acid by the human multidrug resistance protein MRP
Author(s) -
Zaman Guido J.R.,
Cnubben Nicole H.P.,
van Bladeren Peter J.,
Evers Raymond,
Borst Piet
Publication year - 1996
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(96)00718-1
Subject(s) - glutathione , conjugate , chemistry , multiple drug resistance , multidrug resistance associated proteins , biochemistry , glutathione s transferase , pharmacology , enzyme , transporter , biology , atp binding cassette transporter , mathematical analysis , mathematics , gene , antibiotics
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 ‐transferase activity, but also 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.