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Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany [G. J., I. L., U. B., D. K.], and Division of Biology, Kansas State University, Manhattan, Kansas 66506 [M. C.]
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[
-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.
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.).
2 To whom requests for reprints should be addressed.
Received 7/ 8/94. Accepted 8/ 3/94.
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M. Saxena and G. B. Henderson ATP-dependent Efflux of 2,4-Dinitrophenyl-S-glutathione J. Biol. Chem., March 10, 1995; 270(10): 5312 - 5319. [Abstract] [Full Text] [PDF]
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G. Jedlitschky, B. Burchell, and D. Keppler The Multidrug Resistance Protein 5 Functions as an ATP-dependent Export Pump for Cyclic Nucleotides J. Biol. Chem., September 22, 2000; 275(39): 30069 - 30074. [Abstract] [Full Text] [PDF]
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K.-i. Ito, S. L. Olsen, W. Qiu, R. G. Deeley, and S. P. C. Cole Mutation of a Single Conserved Tryptophan in Multidrug Resistance Protein 1 (MRP1/ABCC1) Results in Loss of Drug Resistance and Selective Loss of Organic Anion Transport J. Biol. Chem., May 4, 2001; 276(19): 15616 - 15624. [Abstract] [Full Text] [PDF]
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J. Wijnholds, C. A. A. M. Mol, L. van Deemter, M. de Haas, G. L. Scheffer, F. Baas, J. H. Beijnen, R. J. Scheper, S. Hatse, E. De Clercq, et al. Multidrug-resistance protein 5 is a multispecific organic anion transporter able to transport nucleotide analogs PNAS, June 20, 2000; 97(13): 7476 - 7481. [Abstract] [Full Text] [PDF]
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