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膜系统的表面性质:氯胺酮与神经节苷脂和线粒体脂质单分子膜的相互作用

Surface properties of membrane systems: interaction of ketamine with monomolecular films of ganliosides and mitochondrial lipids.

作者信息

Colacicco G, Burnell J M, Basu M K

出版信息

J Pharm Sci. 1979 Oct;68(10):1246-50. doi: 10.1002/jps.2600681013.

DOI:10.1002/jps.2600681013
PMID:512853
Abstract

Ketamine solutions did not form a film (pi=0) but had an appreciable surface potential (delta V=500 mv), indicating a significant array of +/- oriented charge dipoles at the air-water interface, as opposed to calcium chloride solutions whose delta V was zero. The delta V values of ganglioside films spread on the aqueous phase varied in the order water less than sodium chloride less than calcium chloride less than ketamine hydrochloride. At equivalent concentrations, calcium chloride was 500 times as effective as sodium chloride, and ketamine at the clinical concentrations of 10-20 microgram/ml (36-72 micrometer) was 6000 times as effective as calcium chloride in raising the surface potential of gangliosides; the delta V effect with mitochondrial lipid was in the reverse order; water less than sodium chloride = ketamine hydrochloride less than calcium chloride. This calcium-ketamine inversion indicates a unique specificity of ketamine for gangliosides. Since ketamine acts on the brain and did not affect mitochondrial respiration, the surface potential data suggest that part of the mechanism of action of ketamine could be its interaction with synaptic surfaces and, specifically, with the sialic acid of gangliosides and/or glycoproteins present on the synaptic membrane surface.

摘要

氯胺酮溶液不会形成薄膜(π = 0),但具有可观的表面电位(ΔV = 500 mV),这表明在空气 - 水界面存在大量的±取向电荷偶极子,这与氯化钙溶液的ΔV为零形成对比。铺展在水相上的神经节苷脂薄膜的ΔV值变化顺序为:水<氯化钠<氯化钙<盐酸氯胺酮。在等效浓度下,氯化钙提高神经节苷脂表面电位的效果是氯化钠的500倍,而临床浓度为10 - 20微克/毫升(36 - 72微摩尔)的氯胺酮提高神经节苷脂表面电位的效果是氯化钙的6000倍;线粒体脂质的ΔV效应顺序相反:水<氯化钠 = 盐酸氯胺酮<氯化钙。这种钙 - 氯胺酮的反转表明氯胺酮对神经节苷脂具有独特的特异性。由于氯胺酮作用于大脑且不影响线粒体呼吸,表面电位数据表明氯胺酮作用机制的一部分可能是其与突触表面的相互作用,特别是与突触膜表面存在的神经节苷脂和/或糖蛋白的唾液酸的相互作用。

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