Mechanism of Biological Membrane Damage Induced by Amphiphilic Drugs and Peptides

本研究考察了各种两亲性药物和多肽对生物膜K~(++)的增透作用。使用的细胞是人红细胞、金黄色葡萄球菌、大肠杆菌和大鼠腹膜肥大细胞。作为一个典型的例子，我们描述了Mastoparan的结果。除金黄色葡萄球菌外，该多肽不能有效提高细胞的K~+通透性。在通透性增强的浓度范围内，金黄色葡萄球菌细胞也有膜磷脂的释放。Mastoparan刺激肥大细胞释放组胺，不依赖于K~+的少量外流。Mastoparan对外膜结构预先被化学破坏的大肠杆菌细胞有明显的效果，表明该肽可以增强革兰氏阳性和阴性细菌的细胞膜通透性。在使用脂质体的实验中，马斯托卡兰增加了由卵磷脂酰乙醇胺和卵磷脂酰甘油组成的脂质体的通透性，而对由卵磷脂酰胆碱和胆固醇组成的脂质体显示出较弱的活性。后者的结果与该肽对红细胞和肥大细胞的弱作用密切相关，在红细胞和肥大细胞中酸性脂类只占很小的一部分。Mastoparan降低了双棕榈酰磷脂酰甘油脂质体的相变温度。但不影响二棕榈酰磷脂酰胆碱脂质体的稳定性。这些结果表明，马兜铃素渗透到以酸性磷脂为主的膜中，破坏了膜的结构，增加了膜的通透性。其他多肽的结果可以通过本文背面描述的参考文献看到。

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.