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

• 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
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05671795/
• 关键词: Transdermal drug penetration; Small intestinal brush border membrane; Membrane fluidity; Alcohol; Fatty acid; Mg^<2+>-ATPase; Liposome; Fluorescence probe; アルカリ性ホスファターゼ

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.

以小肠刷状缘膜和皮肤为材料，研究了醇类和脂肪酸类两亲性化合物对生物膜功能的修饰机理。本文观察了七种正丁醇、异戊醇和苯甲醇对兔小肠刷状缘膜Mg^<2+>-ATPase活性的影响，并探讨了它们与膜脂双层流动性变化的关系。所有醇类对膜酶Mg^<2+>-ATPase活性的降低程度明显与它们对二苯基己三烯（DPH）荧光各向异性的降低程度相对应。这些结果表明，醇类对该酶的抑制作用可能是通过扰动刷状缘膜的脂双层来解释的.通过监测DPH的荧光各向异性，还研究了角质层脂质体的脂双层在不同pH值下的相变.随着pH从6.2降低到4.0，这种降低依赖于脂质体中棕榈酸的含量，并与脂肪酸阴离子形式的质子化相对应。在酸性条件下，苯酚的体外透皮吸收受到抑制，这与脂质体的结果一致。在用其它脂肪酸代替棕榈酸时，也观察到脂质体的相变温度的pH依赖性降低。在pH 4.0的月桂酸的存在下，DPH的荧光各向异性也降低在生理温度下，这种效果是类似的长链顺式不饱和脂肪酸。

项目成果

Shuji Kitagawa: "Relationship of Alcohols-induced Canges in Mg^<2+>-ATPase Activity of Rabbit Intestinal Brush Border Membrane with Changes in Fluidity of Its Lipid Bi.layer" The Journal of Membrane Biology. 146(in press). (1995)

Shuji Kitakawa：“酒精诱导的兔肠刷状缘膜 Mg^2-ATP 酶活性变化与其脂质双层流动性变化的关系”膜生物学杂志。

S.Kitagawa, Y.Sugaya, M.Nishizawa and H.Hirata: "Relationship of alcohols-induced changes in Mg^<2+>-ATPase activity of rabbit intestinal brush border membrane with changes in fluidity of its lipid bilayr" Journal of Membrane Biology. 146 (2) (in press).

S.Kitakawa、Y.Sugaya、M.Nishizawa 和 H.Hirata：“醇诱导的兔肠刷状缘膜 Mg^2-ATP 酶活性变化与其脂质双层流动性变化的关系”膜杂志

S.Kitagawa, N.Yokochi and N.Murooka: "pH-Dependence of phase transitiion of the lipid bilayr of liposomes of stratum corneum" International Journal of Pharmaceutics. (in press). (1995)

S.Kitakawa、N.Yokochi 和 N.Murooka：“角质层脂质体脂质双层相变的 pH 依赖性”国际药剂学杂志。

Shuji Kitagawa: "pH-Dependence of Phase Transition of the Lipid Bilayer of Liposomes of Stratum Corneum Lipids" International Journal of pharmaceutics. in press. (1995)

Shuji Kitakawa：“角质层脂质脂质体双层相变的 pH 依赖性”国际药剂学杂志。

Shuji. Kitagawa: "Relationship of Alcohols-induced Changes in Mg^<2+>-ATPase Activity of Rabbit Intestinal Brush Border Membrane with Changes in Fluidity of Its Lipid Bilayer" The Journal of Membrane Biology. 146(in press). (1995)

修吉。