Biophysical and Biochemical Studies on the Mechanisms of Modifications of Biological Membrane Functions by Amphiphilic Alkyl Compounds

两亲性烷基化合物修饰生物膜功能机制的生物物理和生化研究

基本信息

批准号：
05671795
负责人：
KITAGAWA Shuji
金额：
$ 1.34万
依托单位：
Niigata College of Pharmacy
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

项目摘要

Mechanisms of modification of biological membrane functions by amphiphilic compounds such as alcohols and fatty acids were studied for small intestinal brush border membrane and skin. The effects of seven n-alkyl alcohols (from n-butyl to n-undecyl alcohol) , isoamyl alcohol and benzyl alcohol on activity of membrane enzyme Mg^<2+>-ATPase of the rabbit small intestinal brush border membrane were examined and their relationships with changes in fluidity of the membrane lipid bilayr were investigated. The extents of decreases in activeties of the membrane enzyme Mg^<2+>-ATPase by all the alcohols clearly corresponded with their extents of decreases in fluorescence anisotropy of diphenylhexatriene (DPH) . These results suggest the possibility that inhibition of this enzyme by the alcohols can be explained by perturbation of the lipid bilayr of the brush border membrane.Phase transition of the lipid bilayr of liposomes of stratum corneum lipids was also examined at different pH values by monitoring the fluorescence anisotropy of DPH.The phase transition temperature decreased about 15 deg. C with decrease of the pH from 6.2 to 4.0. The decrease depended on the content of palmitic acid en liposomes and corresponded with the protonation of the anionic form of fatty acid. Stumulation of in vitro transdermal penetration of phenol at acidic pH was observed which was consistent with the results on liposomes. A pH-dependent decrease of the phase transition temperature of liposomes was also observed on replacement of palmitic acid by other fatty acids. In the presence of lauric acid at pH 4.0, the fluorescence anisotropy of DPH also decreased at physiological temperatures, this effect being similar to those of long-chain cis-unsaturated fatty acids.

研究了小肠刷状缘膜和皮肤的两亲性化合物（例如醇和脂肪酸）修饰生物膜功能的机制。考察了七种正烷基醇（从正丁醇到正十一醇）、异戊醇和苯甲醇对家兔小肠刷状缘膜膜酶Mg^2+-ATP酶活性的影响，并探讨了其对小肠刷状缘膜酶活性的影响。研究了与膜脂双层流动性变化的关系。所有醇对膜酶Mg 2+ -ATP酶活性的降低程度明显与其对二苯基己三烯(DPH)的荧光各向异性的降低程度相对应。这些结果表明，醇类对该酶的抑制可以通过刷状缘膜的脂质双层的扰动来解释。通过监测角质层脂质的脂质体的脂质双层在不同pH值下的相变也进行了检查。 DPH的荧光各向异性。相变温度降低约15℃。 C，pH值从6.2降低到4.0。这种减少取决于脂质体中棕榈酸的含量，并且与脂肪酸阴离子形式的质子化相对应。观察到在酸性pH下对苯酚体外透皮渗透的刺激，这与脂质体上的结果一致。当用其他脂肪酸替代棕榈酸时，还观察到脂质体相变温度的 pH 依赖性降低。在pH 4.0的月桂酸存在下，DPH的荧光各向异性在生理温度下也降低，这种效果与长链顺式不饱和脂肪酸的效果相似。