The action of pimaricin, etruscomycin and amphotericin B on liposomes with varying sterol content

Abstract

1. 1. The effect of pimaricin, etruscomycin and amphotericin B on the K+ release from liposomes is strongly dependent on their sterol concentration.Pimaricin and etruscomycin induce K+ release from egg lecithin liposomes with cholesterol contents of more than 25 and 10 mol%, respectively, at polyene concentrations of 100 and 10 μg/ml, respectively. Amphotericin B shows a maximal effect at a cholesterol content of 20 mol% at a concentration of 0.4 μg/ml.

2. 2. For liposomes containing ergosterol the sensitivity is shifted to a lower sterol content. All three polyenes show activity at 10 mol% ergosterol. The sensitivity for amphothericin B is increased approx. 15 times by the incorporation of ergosterol compared to cholesterol. The increase in sensitivity is much less for pimaricin and etruscomycin. The K+ release is maximal at an ergosterol concentration of 30 mol%.

3. 3. Pimaricin, etruscomycin and amphotericin B can induce K+ release from erythrocytes without the release of haemoglobin at concentrations of 20, 2 and 1 μg/ml, respectively. For these polyenes a selective permeability change is also demonstrated for liposomes since K+ is released but no [14C] dextran. Filipin shows a nonselective release of solutes from erythrocytes and liposomes.

4. 4. At cholesterol concentrations higher than 20 mol% and ergosterol concentrations higher than 10 mol%, etruscomycin, pimaricin and amphotericin B show little dependence of the bilayer thickness and are able to release K+ from didocosenoyl phosphatidylcholine liposomes after addition of the polyene to one side of the membrane.

A possible mechanism is discussed.