Effects of amphotericin B on membrane permeability--kinetics of spin probe reduction.
The effect of the polyene antibiotic amphotericin B on the permeability of both unilamellar and multilamellar model membranes is investigated. The method measures the loss of the electron paramagnetic resonance signal of a spin probe, trapped in the aqueous compartment of a lipid dispersion, upon addition of ascorbate ions to the bulk aqueous phase. Amphotericin B causes large increases in the permeability of cholesterol-containing egg phosphatidylcholine membranes, whereas the effects are small in the absence of sterol and do not depend on surface charge. The effect of amphotericin depends upon the antibiotic:sterol mole ratio. The antibiotic appears to be unable to cross the membrane, acting only on the outermost bilayer of a multibilayer dispersion. When a phospholipid in the gel phase is used, amphotericin B causes large increases in permeability, independently of the presence or absence of sterol. It is suggested that the mechanism of action of amphotericin B is different for lipids in the liquid crystalline or gel states.
D000666:Amphotericin B / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002784:Cholesterol / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D007700:Kinetics; D008051:Lipid Bilayers / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism; D013499:Surface Properties
D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D000666:Amphotericin B; D002784:Cholesterol; D004121:Dimethyl Sulfoxide