Studies on the mode of action of excess of vitamin A. 9. Penetration of lipid monolayers by compounds in the vitamin A series.
Studies on the mode of action of excess of vitamin A. 9. Penetration of lipid monolayers by compounds in the vitamin A series.
复制标题
研究过量维生素A的作用方式。9.维生素A系列化合物对脂质单层的渗透。
作者：
A. Bangham;J. Dingle;J. Lucy
维生素A1酒精已被证明能溶血红细胞(Dingle&Lucy，1962)。它还能够分解成纤维细胞的细胞膜和核膜，并导致它们的线粒体肿胀(Dingle，Glauert，Daniel&Lucy，1962)。线粒体肿胀是由Jackson&Fall(1963)在体外研究维生素A1酒精对鸡胚胎皮肤表皮精细结构的影响时观察到的。在对分离的亚细胞组分的研究中，人们发现维生素A1酒精从分离的溶酶体中释放出一种蛋白水解酶(Dingle，1961；Fall，Dingle&Webb，1962)，并导致分离的大鼠肝脏线粒体迅速膨胀(Lucy，Luscombe&Dingle，1963)。维生素A对红细胞以及对分离的溶酶体和线粒体的作用已被证明具有高度的分子特异性。因此，溶血活性是维生素A1、醇和醛的一种性质，密切相关的分子只在很小程度上具有这种性质。由于溶血活性与穿透胆固醇膜或分散蛋白质膜的能力有关(Schulman&RIdead，1937a，b)，因此研究了维生素A系列化合物在空气-水界面穿透脂膜的能力。过去已经研究了一个分子物种穿透另一个分子物种的部分压缩单分子膜的过程，但大多数所研究的化合物之所以被选择，更多是因为它们的已知表面活性，而不是它们的生物学意义。然而，Skou(1961)表明，局部麻醉剂的效力与其穿透神经组织脂类的能力之间存在关系。最近的研究表明，抗组胺药物和十六烷基三甲基溴化铵对四氯化碳诱导的大鼠肝脏坏死的预防作用与这些化合物对单胺类药物的穿透能力之间存在相关性。
Vitamin A1 alcohol has been shown to haemolyse erythrocytes (Dingle & Lucy, 1962). It is also able to disintegrate the cell and nuclear membranes of fibroblasts and to cause their mitochondria to swell (Dingle, Glauert, Daniel & Lucy, 1962). Mitochondrial swelling has been observed by Jackson & Fell (1963) in a study of the epidermal fine structure of embryonic chick skin under the influence of vitamin A1 alcohol in vitro. In investigations of isolated subcellular fractions, it has been found that vitamin A1 alcohol liberates a proteolytic enzyme from isolated lysosomes (Dingle, 1961; Fell, Dingle & Webb, 1962) and causes isolated rat-liver mitochondria to swell rapidly (Lucy, Luscombe & Dingle, 1963). The action of vitamin A on erythrocytes and on isolated lysosomes and mitochondria has been shown to have a high degree of molecular specificity. Thus haemolytic activity is a property of vitamin A1 alcohol and aldehyde that is possessed in only a small degree by closely related molecules. Since haemolytic activity is associated with a capacity to penetrate cholesterol films or to disperse protein films (Schulman & Rideal, 1937 a, b), the ability of compounds in the vitamin A series to penetrate lipid films at an air-water interface has been investigated. The process of penetration by one molecular species into a partially compressed monolayer of another molecular species has been studied in the past but most of the compounds investigated were chosen more because of their known surface-active properties than for their biological importance. However, Skou (1961) showed that a relationship exists between the potency of a local anaesthetic and its ability to penetrate lipids of nerve tissue. More recently it has been demonstrated that there is a correlation between the prevention of carbon tetrachlorideinduced necrosis in rat liver by antihistamines, and by cetyltrimethylammonium bromide, and the capacity of these compounds to penetrate a mono-