Functional implications from the effects of 1-chloro-2,4-dinitrobenzene and ethacrynic acid on efflux routes for methotrexate and cholate in L1210 cells.

摘要: 1-Chloro-2,4-dinitrobenzene (CDNB) and ethacrynic acid were examined for the ability to inhibit unidirectional efflux routes in L1210 cells that extrude both methotrexate cholate (system I) alone II). These electrophiles selected study because of their known undergo rapid intracellular conversion glutathione conjugates. CDNB produced typical inhibitor kinetics was a moderate system I (IC50 = 4.8 microM) II 7.5 with as substrate. However, complex response observed when employed an alternative substrate I. Cholate stimulated initially at low levels CDNB, but then slowed net inhibition concentrations exceeded 10 microM. The latter characteristics not acid, which comparable regardless 4.6 microM). Efflux measurements L1210/C7 variant lacks confirmed stimulates activity substantial unique III). by reversed wash step required removal subsequent incubation 37 degrees C. This slow reversal attributed time-dependent clearance inhibitory A correlation between systems anions anionic conjugates demonstrated further prostaglandin A1 indomethacin, two potent inhibitors efflux, 2,4-dinitrophenyl-S-glutathione. results support hypothesis are part family pumps function vivo various