title: ATPase activity of purified plasma membranes and digestive vacuoles from Plasmodium falciparum.
abstract: The ATPase activity of the human malaria parasite, Plasmodium falciparum was investigated using two experimental systems, (i) digestive vacuoles, and (ii) purified plasma membranes isolated from a chloroquine-sensitive and a chloroquine-resistant strain. No correlation between the level of ATPase activity and chloroquine sensitivity could be detected. In both systems, the ATPase activity of the chloroquine-resistant and -sensitive strain was decreased in the presence of the P-glycoprotein inhibitor vanadate. Susceptibility to inhibition by vanadate together with the lack of effect of ouabain implies a P-type ATPase activity in the plasma membrane. Furthermore, the inhibition of Fac8 ATPase activity by oligomycin both in the digestive vacuoles and the plasma membranes would be consistent with higher levels of Pgh1 in Fac8. Our data are consistent with the presence of a V-type H+-ATPase in the parasite food vacuole. Bafilomycin A1 and N-ethylmaleimide decreased the vacuolar ATPase activity in both chloroquine-resistant and -sensitive strains. Interestingly, a 30% decrease was observed between the ATPase activity of plasma membranes isolated from Fac8 and D10 in the presence of bafilomycin A1, suggesting the presence of a V-type ATPase in D10 plasma membrane that is underexpressed or altered in the plasma membrane of the chloroquine-resistant Fac8. The chemosensitisers tested had no effect on the ATPase activity of chloroquine-resistant P. falciparum in both systems suggesting that their activity is not mediated through an ATP-dependent mechanism. No effect was observed on the vacuolar ATPase activity in the presence of the antimalarials tested indicating that an ATP-dependent transport has not been activated.
authors.affiliation: Department of Pharmacology, University of Cape Town, Medical School, Observatory 7925, South Africa.
authors.forename: Laurence M
authors.initials: LM
authors.lastname: Elandalloussi
authors.forename: Bronwen
authors.initials: B
authors.lastname: Adams
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Smith
mesh_terms: D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D037621:Artemisinins / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D002738:Chloroquine / Q000494:pharmacology; D004351:Drug Resistance; D015767:Mefloquine / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D011803:Quinine / Q000494:pharmacology; D012717:Sesquiterpenes / Q000494:pharmacology; D013347:Subcellular Fractions / Q000378:metabolism; D014617:Vacuoles / Q000187:drug effects / Q000201:enzymology
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; D002738:Chloroquine; C031327:artemisinin; D011803:Quinine; D000251:Adenosine Triphosphatases; D015767:Mefloquine