Arsenite-resistant Leishmania donovani promastigotes express an enhanced membrane P-type adenosine triphosphatase activity that is sensitive to verapamil treatment

An arsenite-resistant strain of Leishmania donovani was generated in vitro by sequential exposure to higher concentrations of sodium m-arsenite. The r esistant strain displayed a low level of cross-resistance to structurally u nrelated drugs such as doxorubicin and pentamidine. This cross-resistance w as sensitive to the calcium-channel blocker verapamil. The membrane-associa ted P-type adenosine triphosphatase (ATPase) activity detected in crude mem brane fractions of the resistant strain was 3-fold that found in the wild-t ype parasites. The enhanced ATPase activity was unaffected by the presence of verapamil in the reaction mixture. However, when cells were grown in the presence of verapamil the membrane-associated ATPase activity of the resis tant strain showed significant inhibition.