Concentration and time dependence of amphotericin B-induced permeability changes across plasma membrane vesicles from Leishmania sp.
The main purpose of this paper is to show that the polyene antibiotic amphotericin B may form two types of channels in plasma membrane vesicles from Leishmania sp.: ionic and aqueous. The experimental design was to follow the light scattering changes of a suspension of membrane vesicles under an osmotic shock. The results show that a low concentration of amphotericin B(0.2 to 0.8 microM) led to an enhancement of urea and salt permeability without affecting the total osmotic response of Leishmania vesicles. Such an increment of solute permeability induced by low concentrations of amphotericin B was 100% blocked by tetraethylammonium. Low concentrations of amphotericin B were also able to induce an enhancement of glucose permeability but only after Leishmania membrane vesicles were incubated for 15 min with the antibiotic, previous to mixing. On the other hand, high amphotericin B concentrations (greater than 0.8 microM) induced a decrease in the total extent of shrinkage of membrane vesicles immediately after its mixing with urea solutions. At this high concentration of amphotericin B the blocking of tetraethylammonium was reduced by 50%. These results support the authors' previous conclusion (1) that in ergosterol-containing membranes, amphotericin B may form two different types of channels differing in internal diameter.
Department of Cell Biology, Faculty of Sciences, Central University of Venezuela, Caracas.
B E
BE
Cohen
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Gamargo
D000666:Amphotericin B / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D007891:Leishmania / Q000187:drug effects*; D011188:Potassium / Q000378:metabolism; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013997:Time Factors; D014508:Urea / Q000378:metabolism
D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D000666:Amphotericin B; D014508:Urea; D005947:Glucose; D011188:Potassium