Presence of a Na(+)/H(+) exchanger in acidocalcisomes of Leishmania donovani and their alkalization by anti-leishmanial drugs.
Acidocalcisomes are acidic vacuoles present in trypanosomatids that contain most of the cellular calcium. The data presented here demonstrate that Leishmania donovani acidocalcisomes possess a Na(+)/H(+) exchanger. 3,5-Dibutyl-4-hydroxytoluene, in the concentration range of 0-20 microM, inhibited the Na(+)/H(+) exchanger, and strongly stimulated the activity of the vacuolar H(+)-ATPase responsible for vacuolar acidification. As occurs with Na(+), the cationic anti-leishmanial drugs pentamidine, WR-6026, and chloroquine promoted a fast and extensive alkalization of the L. donovani acidocalcisomes.
Vercesi
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Laboratory of Molecular Parasitology, Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 S. Lincoln Avenue, Urbana, IL, USA.
Rodrigues
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Catisti
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D000165:Acridine Orange; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000634:Aminoquinolines / Q000494:pharmacology; D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D002084:Butylated Hydroxytoluene / Q000031:analogs & derivatives / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007893:Leishmania donovani / Q000187:drug effects* / Q000378:metabolism; D010419:Pentamidine / Q000494:pharmacology; D012965:Sodium Chloride / Q000494:pharmacology; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D014617:Vacuoles / Q000187:drug effects* / Q000378:metabolism
D000634:Aminoquinolines; D000981:Antiprotozoal Agents; D017923:Sodium-Hydrogen Exchangers; D000643:Ammonium Chloride; D002084:Butylated Hydroxytoluene; D012965:Sodium Chloride; D010419:Pentamidine; D002738:Chloroquine; D000255:Adenosine Triphosphate; C037667:3,5-di-tert-butyl-4-hydroxytoluene; D000165:Acridine Orange; C080436:8-aminoquinoline