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.