Mechanism of Biological Membrane Damage Induced by Amphiphilic Drugs and Peptides

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In this research, the K^+ permaebility-increasing actions of various amphiphilic drugs and peptides on biomembranes were examined. Cells used were human erythrocytes, Staphylococcus aureus, Escherichia coli and rat peritoneal mast cells. We described here the results of mastoparan as a typical example. This peptide did not efficiently increase the K^+ permeability of cells except for S. aureus. The release of membrane phospholipids was also observed from S. Baureus cells in the concentra tion range of the permeability enhancement. Mastoparan stimulated histamine release from mast cells, independently of a small efflux of K^+. Mastoparan became markedly effective to E. coli cells whose outer membrane structure was chemically disrupted beforehand, showing that the peptide can enhance the permeability of the cytoplasmic membranes of both Gram-positive and -negative bacteria. In experiments using liposomes, mastoparan increased the permeability of the liposomes composed of egg phoshatidylethanolamine and egg phosphatidylglycerol, which are the lipid constituents of the cytoplasmic membrane of E. colls, while it showed a weak activity to the liposomes composed of egg phosphatidylcholine and cholesterol. The latter result related closely to the fact that this peptide acted weakly on erythrocytes and mast cells in which acidic lipids constitute a minor portion. Mastoparan decreased the phase transition temperature of dipalmitoylphosphatidylglycerol liposomes. but it did not affect that of dipalmitoylphosphatidylcholine liposomes. These results indicate that mastoparan penetrated into membranes mainly containing acidic phospholipids and disrupted the membrane structure to increase the permeability. The results of other peptides can be seen through referencEs described on the back of this paper.