title: The water and ionic permeability induced by polyene antibiotics across plasma membrane vesicles from Leishmania sp.
abstract: An osmotic method has been used to study the effect of the polyene antibiotics amphotericin B, nystatin and candicidin on the water permeability of plasma membranes prepared from Leishmania sp. The effect of amphotericin B on the permeability of Leishmania membranes to a salt such as potassium nitrate was also investigated. A non-linear and saturable enhancement of water and salt permeability was measured with increasing polyene concentrations, which could be adjusted to Hill cooperativity equation. The antibiotic concentrations that induce at 30 degrees C half-maximal effects on the water permeability of Leishmania vesicles were 0.021 microM for candicidin, 0.21 microM for amphotericin B and 1.4 microM for nystatin. At 30 degrees C, the concentration of amphotericin B required to induce half of the maximal effect on the permeability of Leishmania vesicles to potassium nitrate was 1.8 microM. The temperature dependence for amphotericin B, nystatin and candicidin enhancement of the water permeability of Leishmania vesicles was determined by using Q10 data at 20 and 30 degrees C. The estimated activation energies at increasing polyene concentrations display the same general pattern for all three polyene antibiotics investigated, that is, a maximal positive value at about the polyene concentrations required for half-maximal effect. The significance of these results for understanding the mechanisms of action of polyene antibiotics on natural membranes is discussed.
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology*; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D002174:Candicidin / Q000494:pharmacology*; D002458:Cell Fractionation; D002463:Cell Membrane Permeability / Q000187:drug effects; D002474:Cell-Free System; D004305:Dose-Response Relationship, Drug; D004875:Ergosterol / Q000502:physiology; D066298:In Vitro Techniques; D007891:Leishmania / Q000187:drug effects*; D009566:Nitrates / Q000378:metabolism; D009761:Nystatin / Q000494:pharmacology*; D017680:Potassium Compounds; D014882:Water-Electrolyte Balance / Q000187:drug effects
chemical_list: D000935:Antifungal Agents; D009566:Nitrates; D017680:Potassium Compounds; D009761:Nystatin; D002174:Candicidin; D000666:Amphotericin B; C023844:potassium nitrate; D004875:Ergosterol