The addition of amphotericin methyl ester (AME) to suspensions of is followed by a progressively increasing rate of release of K from within the cell. The time taken for a given rate of release to be reached depends upon the AME concentration (the product of AME concentration and time being approximately constant), the pH and concentration of buffer, the temperature, the suspension density, and the phase of growth of the organisms. The sensitivity of to AME decreases during the growth of a batch culture, rapid decrease occurring after the organisms have reached the stationary phase of growth. The induction of K release does not occur at 0 °C and shows a high temperature coefficient over the range 15 to 30 °C.

Suspensions of mouse LS cells are 10 to 30 times less sensitive than towards AME, amphotericin B and nystatin; the two types of cell display little difference in sensitivity towards perimycin and candicidin, while mouse LS cells are more sensitive than towards filipin. Addition of sterols at the same time as AME increases the time taken for the release of K to reach a given rate; of the sterols tested, zymosterol was the most effective in antagonizing AME, while ergosterol was approximately twice as effective as cholesterol on a molar basis. When organisms were exposed to AME for a short time, removed and resuspended in the absence of drug, the rate of K release continued to increase; this increase was prevented by ergosterol: 2 x 10 M-ergosterol prevented further damage after organisms had been exposed to 10 M AME.


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