title: Mechanism of action of amphotericin B on Leishmania donovani promastigotes.
abstract: The growth of Leishmania donovani promastigotes in a liquid medium was completely inhibited by amphotericin B at a concentration of 0.3 microgram ml-1 (0.3 microM). Continuous release of small molecules that absorb at 260 nm and 280 nm was observed after contact with the drug. Uptake of [U-14C]glucose was inhibited in cells treated with the drug. An immediate release of isotopic glucose and its metabolites from preloaded cells could be demonstrated after incubation with amphotericin B (0.4 microM). Inhibition of respiration by the drug was a comparatively slower process. All the above effects could be effectively prevented in the presence of either cholesterol or ergosterol. The primary site of action of amphotericin B on L. donovani promastigote cells appears to be membrane sterols that result in a loss of the permeability barrier to small metabolites. An interesting biochemical similarity, thus, emerges between flagellated protozoa and fungi.
mesh_terms: D000666:Amphotericin B / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D002784:Cholesterol / Q000494:pharmacology; D004875:Ergosterol / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D007893:Leishmania donovani / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects
chemical_list: D000666:Amphotericin B; D002784:Cholesterol; D005947:Glucose; D004875:Ergosterol