Abstract
The ATP-dependent transport of the endogenous glutathione conjugate leukotriene C4 (LTC4) was more than 25-fold higher in membrane vesicles prepared from human leukemia cells (HL60/ADR) overexpressing the multidrug resistance-associated protein than from drug-sensitive parental HL60 cells or revertant cells. Similar results were obtained with S-(2,4-dinitrophenyl)glutathione as substrate. Photoaffinity labeling detected preferentially in the HL60/ADR membranes a 190-kilodalton protein binding [3H]LTC4 and 8-azido[α-32P]ATP. The [3H]LTC4-labeled 190-kilodalton protein was immunoprecipitated by an antiserum against the COOH-terminal sequence of multidrug resistance-associated protein. Our results indicate that multidrug resistance-associated protein mediates the ATP-dependent transport of LTC4 and structurally related anionic amphiphilic conjugates.
Footnotes
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↵1 This work was supported in part by the Deutsche Forschungsgemeinschaft through SFB 352, Heidelberg (D. K.), and by USPHS Grant CA-37585 from the National Cancer Institute (M. C.).
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↵2 To whom requests for reprints should be addressed.
- Received July 8, 1994.
- Accepted August 3, 1994.
- ©1994 American Association for Cancer Research.
Volume 54, Issue 18
