title: Uptake of the antileishmania drug tafenoquine follows a sterol-dependent diffusion process in Leishmania.
abstract: OBJECTIVE
  The present study was designed to elucidate the mechanism of tafenoquine uptake in Leishmania and its sterol dependence.
  
  
  METHODS
  Because tafenoquine is a fluorescent compound, spectrofluorimetric analysis allowed us to monitor its uptake by Leishmania promastigotes and intracellular amastigotes, and to evaluate the effect of temperature, energy and H+ gradient on drug entry. The influence of sterols on tafenoquine uptake in Leishmania parasites was determined in experiments using sterol-depleting agents such as methyl-β-cyclodextrin or cholesterol oxidase.
  
  
  RESULTS
  Tafenoquine exhibited fast entry kinetics into Leishmania in an energy-independent, but pH- and temperature-dependent, non-saturable process. Furthermore, sterol depletion decreased tafenoquine uptake.
  
  
  CONCLUSIONS
  These findings suggest that Leishmania takes up tafenoquine by a diffusion process and that decreases in membrane sterol content may induce a decrease in drug uptake.
authors.affiliation: Instituto de Parasitología y Biomedicina López-Neyra, CSIC (IPBLN-CSIC), Parque Tecnológico de Ciencias de la Salud, Avda. del Conocimiento s/n, 18100 Armilla, Granada, Spain.
authors.forename: José Ignacio
authors.initials: JI
authors.lastname: Manzano
authors.forename: Luis
authors.initials: L
authors.lastname: Carvalho
authors.forename: Raquel
authors.initials: R
authors.lastname: García-Hernández
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Poveda
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Ferragut
authors.forename: Santiago
authors.initials: S
authors.lastname: Castanys
authors.forename: Francisco
authors.initials: F
authors.lastname: Gamarro
mesh_terms: D000634:Aminoquinolines / Q000378:metabolism* / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000378:metabolism* / Q000494:pharmacology; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D002789:Cholesterol Oxidase / Q000378:metabolism; D004058:Diffusion; D006863:Hydrogen-Ion Concentration; D018320:Leishmania major / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D013261:Sterols / Q000378:metabolism; D013696:Temperature; D047392:beta-Cyclodextrins / Q000494:pharmacology
chemical_list: D000634:Aminoquinolines; D000981:Antiprotozoal Agents; D013261:Sterols; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; C055852:tafenoquine; D002789:Cholesterol Oxidase