Transport of glutathione, glucuronate, and sulfate conjugates by the MRP gene-encoded conjugate export pump.

摘要: Previous studies have identified the ATP-dependent export of glutathione conjugates as a physiological function multidrug resistance protein (MRP). The involvement MRP in transport endogenous and xenobiotic was investigated further using membrane vesicles from -transfected HeLa cells. [3H]leukotriene C4, S -(2,4-dinitrophenyl)-[3H]glutathione, 3H-labeled oxidized characterized by determination efficiency Vmax: K m amounting to 1031, 114, 7.1 ml × mg protein-1 min-1, respectively. Additional substrates for MRP-mediated included steroid conjugate 17β-glucuronosyl [3H]estradiol bile salt [6α-14C]glucuronosylhyodeoxycholate 3α-sulfatolithocholyl [3H]taurine. value 1.5 ± 0.3 µm, with ratio 42 i 0.7 µm leukotriene receptor antagonist MK 571. observed anticancer drug glucuronosyl [3H]etoposide monochloro-mono[3H]glutathionyl melphalan, but not unmodified [14C]doxorubicin, [3H]daunorubicin, or [3H]vinblastine. Our results establish that functions an pump only also glucuronidated sulfated well exogenous compounds.