Reduced ouabain-sensitive potassium entry as a possible mechanism of multidrug-resistance in P388 cells.
Multidrug-resistant P388 cells were found to be resistant also to a variety of ammonium, phosphonium and arsonium compounds. As previously shown for anthracyclines and vinca alkaloids, the resistance to the permanently charged lipophilic cationic compounds could be circumvented by verapamil. Relative to drug-sensitive cells, K+ uptake and plasma membrane Mg-ATPase activity in multidrug-resistant cells are ouabain resistant. The intracellular K+ concentration in drug-resistant cells is maintained at a normal level by increased activity of the furosemide sensitive transport system. It is suggested that the reduced activity of the electrogenic Na(+)-K+ pump in multidrug-resistant, cells could result in a lower transmembrane potential and therefore reduced accumulation of cationic lipophilic compounds.
Department of Oncology, Hadassah University Hospital, Jerusalem, Israel.
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Ramu
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Ramu
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Gorodetsky
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects; D004351:Drug Resistance / Q000502:physiology*; D007941:Leukemia P388 / Q000378:metabolism*; D008564:Membrane Potentials; D051379:Mice; D010042:Ouabain / Q000494:pharmacology*; D010619:Phenazines / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
D010619:Phenazines; D010042:Ouabain; D014700:Verapamil; D011188:Potassium