Increased P-type ATPase activity in Leishmania tropica resistant to methotrexate.

In the present report, we show evidence that the membrane from the protozoan parasite Leishmania tropica (LRC-L39), in vitro resistant to 1 mM of methotrexate (MTX), has a significative increased ATPase activity with respect to wild-type line. This ATPase activity is vanadate sensitive, a characteristic of the P-type ATPases included in the ATP-binding casette (ABC) superfamily of transporters, such as P-glycoprotein involved in the multidrug resistance in mammalian cells. Also, this ATPase activity is not modified by MTX, ammonium molybdate and other detergents such as Triton X-100, Brij 58 and lysophosphatidylcholine. However, unlike the P-glycoprotein, we have observed that the ATPase activity is not stimulated by the drugs verapamil and puromycin. This significative ATPase activity could be related to the overexpressed putative P-glycoprotein, with unknown function in these MTX-resistant parasites.