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 resistant strain displayed a low level of cross-resistance to structurally unrelated drugs such as doxorubicin and pentamidine. This cross-resistance was sensitive to the calcium-channel blocker verapamil. The membrane-associated P-type adenosine triphosphatase (ATPase) activity detected in crude membrane fractions of the resistant strain was 3-fold that found in the wild-type 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 resistant strain showed significant inhibition.
Prasad
V
V
Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Punjab, India.
Kaur
J
J
Dey
C S
CS
D000251:Adenosine Triphosphatases / Q000187:drug effects*; D000818:Animals; D018053:Arsenites / Q000494:pharmacology*; D001693:Biological Transport, Active / Q000187:drug effects; D004351:Drug Resistance; D007893:Leishmania donovani / Q000187:drug effects*; D008565:Membrane Proteins / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology*
D018053:Arsenites; D008565:Membrane Proteins; D014700:Verapamil; D000251:Adenosine Triphosphatases; C015001:arsenite