The MRP gene encodes an ATP-dependent export pump for leukotriene C4 and structurally related conjugates.

摘要: The multidrug resistance-associated protein (MRP) is the product of an ATP-binding cassette transporter gene overexpressed in some tumor cells resistant to antineoplastic agents. We studied transport function MRP membrane vesicles prepared from HeLa transfected with expression vector and overexpressing this 190-kDa glycoprotein. ATP-dependent primary-active into was demonstrated for leukotriene C4 (LTC4), LTD4, LTE4, S-(2,4-dinitrophenyl)glutathione relative rates, at a substrate concentration 50 nM, 1.0, 0.27, 0.14, 0.16, respectively. endogenous glutathione conjugate LTC4 had highest affinity Km 97 nM. ATP 19 microM. Direct photoaffinity labeling [3H]LTC4 labeled predominantly MRP-transfected cells. effectively inhibited by LTD4 receptor antagonist MK 571, whereas cyclosporin A and, particularly, its analog PSC 833 were much less potent. respective Ki values 0.6, 5, 27 microM, In addition, 571 preferentially transfectants. Our results provide direct evidence that encodes export pump conjugates lipophilic compounds several other anionic residues. conclude biosynthetic release mediated gene.