Increased cytosolic pH in multidrug-resistant human lung tumor cells: effect of verapamil.
In a set of four increasingly multidrug-resistant variants of SW-1573 human lung tumor cells, the pHi (i.e., steady-state cytosolic pH) increased up to 0.44 U as a function of the level of doxorubicin resistance. The elevated pHi in the most resistant (2,000-fold) variant dropped to the control level upon addition of verapamil, a known inhibitor of P-glycoprotein activity. These data suggest that, in the absence of xenobiotic substrates, P-glycoprotein activity can affect cellular pHi. This finding may be important for the elucidation of the physiological function of this protein.
Keizer
H G
HG
Department of Toxicology, Duphar B.V., Weesp, The Netherlands.
Joenje
H
H
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins / Q000032:analysis; D003600:Cytosol / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D004351:Drug Resistance; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008175:Lung Neoplasms / Q000473:pathology; D008562:Membrane Glycoproteins / Q000032:analysis*; D017923:Sodium-Hydrogen Exchangers; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D017923:Sodium-Hydrogen Exchangers; D004317:Doxorubicin; D014700:Verapamil; D013755:Tetradecanoylphorbol Acetate