Abood L G, Hoss W
Eur J Pharmacol. 1975 May;32(1):66-75. doi: 10.1016/0014-2999(75)90324-6.
In the course of investigating various membranous components for morphine binding, it was found that the major substance responsible was phosphatidyl serine. Other acidic lipids, such as phosphatidic acid and phosphoinositides bind to a considerably lesser extent, while neutral lipids, glycolipids and other phosphatides bind slightly or not at all. Total lipid extracts from a number of regions of rat brain exhibited different degrees of binding to (-)-morphine, such regions as the cerebral cortex and thalamus being the greatest. From an examination of the pH curve for binding and the effect of ionic strength, it was concluded that the binging was largely electrostatic. The method employed was the radioactive measurement of 14C-morphine adsorption to surface films of phosphatidyl serine. When the phosphatide was dispersed in a nonionic detergent near the critical micelle concentration, adsorption was maximal, attaining a value of 1 molecule of morphine adsorbed per molecule of phosphatidyl serine in the surface micelle. The relation between binding affinity and biological potency was not consistent. Morphine adsorption occurred with films prepared from a dispersion of the phosphatide and a hydrophobic protein from synaptic membranes. With the use of levorphanol and dextrorphan it could be shown that binding of morphine was stereospecific.
在研究各种膜成分与吗啡结合的过程中，发现主要负责的物质是磷脂酰丝氨酸。其他酸性脂质，如磷脂酸和磷酸肌醇的结合程度要小得多，而中性脂质、糖脂和其他磷脂则几乎不结合或根本不结合。从大鼠脑的多个区域提取的总脂质提取物对（-）-吗啡表现出不同程度的结合，其中大脑皮层和丘脑等区域结合程度最大。通过检查结合的pH曲线和离子强度的影响，得出结合主要是静电作用的结论。所采用的方法是通过放射性测量14C-吗啡吸附到磷脂酰丝氨酸表面膜上的情况。当磷脂在接近临界胶束浓度的非离子洗涤剂中分散时，吸附量最大，在表面胶束中每分子磷脂酰丝氨酸吸附1分子吗啡。结合亲和力与生物活性之间的关系并不一致。吗啡能与由磷脂分散体和突触膜中的疏水蛋白制备的膜发生吸附。使用左啡诺和右啡烷可以证明吗啡的结合具有立体特异性。
