Currently, a major problem in the management of visceral leishmaniasis or kala-azar, especially in the Indian subcontinent, is the growing unresponsiveness to conventional antimonial therapy. Membrane bound pyrophophatase (PPases) do not exist in plasma membrane from mammals. Thus, H+
-PPases from Leishmania
plasma membrane might be potential target in rational chemotherapy of the disease caused by Leishmania parasites.
To characterize the activities of inorganic pyrophophatase (PPase) in the plasma membrane of Leishmania donovani
promastigote and amastigote.
Culture method of promastigote and amastigote were developed. We assayed PPase activity in isolated plasma membrane of L. donovani
We characterized K+
-PPase present in the plasma membrane of Leishmania donovani
and investigated its possible role in the survival of promastigote and amastigote. PPase activity was stimulated by K+
ions and sodium orthovanadate, inhibited by pyrophosphate analogs imidodiphosphate and alendronate, KF, DCCD, thiol reagent parachloromercuribenzenesulfonate (PCMBS), N-ethylmaliemide (NEM), phenylarsineoxide, ABC superfamily transport modulator verapamil and was also by F1
-ATPase inhibitor quercetin.
We conclude that there are significant differences within promastigote, amastigote and mammalian host in cytosolic pH homeostasis to merit the inclusion of PPase transporter as putative targets for rational drug design.