Nonanesthetic alcohols dissolve in synaptic membranes without perturbing their lipids.
Nonanesthetic alcohols dissolve in synaptic membranes without perturbing their lipids.
复制标题
非麻醉醇溶解在突触膜中而不扰乱其脂质。
DOI：
10.1073/pnas.86.3.1084
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发表时间：
1989
影响因子：
11.1
通讯作者：
Streicher,P
中科院分区：
文献类型：
--
作者：
Miller,KW;Firestone,LL;Alifimoff,JK;Streicher,P
虽然许多全身麻醉理论假设了脂质作用位点，但对于超过12个碳的高度疏水伯烷醇缺乏麻醉效力（截止值）还没有充分的解释。一些研究表明，这些非麻醉酒精不溶于细胞膜。其他研究反驳了这一观点，认为蛋白质上的麻醉位点提供了更好的解释。在这里，我们表明麻醉十二醇和非麻醉十四醇都同样很好地进入动物组织和分离的突触后膜。用十二醇处理一组豚鼠蝌蚪时，半数被4.7 μ m（游离水浓度）麻醉，组织中相应浓度为0.4 mmol / kg湿重。长时间暴露于十四醇（92小时）会产生更高的组织浓度（0.7 mmol / kg湿重），但没有观察到麻醉作用。此外，全身麻醉剂被认为作用于突触后膜，但两种烷醇都从鱼雷电斑分裂到突触后膜。自旋标签，12-羟基硬脂酸酯，被纳入这些膜。报告的脂质顺序参数被麻醉醇（辛醇、癸醇和十二醇）降低，而非麻醉醇要么没有显著改变它（十四醇），要么实际上增加了它（十六醇和十八醇）。因此，尽管脂溶性不能解释长链醇的效价切断的药理学，脂质扰动提供了一个准确的描述。
While many theories of general anesthesia postulate a lipid site of action, there has been no adequate explanation for the lack of anesthetic potency of the highly hydrophobic primary alkanols with more than 12 carbons (the cut-off). Some work suggests that these nonanesthetic alcohols do not dissolve in membranes. Other work contradicts this and suggests that an anesthetic site on a protein provides a better explanation. Here we show that both the anesthetic dodecanol and the nonanesthetic tetradecanol are taken up equally well into the tissues of animals and into isolated postsynaptic membranes. When a group of Rana pipiens tadpoles were treated with dodecanol, half were anesthetized by 4.7 microM (free aqueos concentration), and the corresponding concentration in the tissues was found to be 0.4 mmol per kg wet weight. Prolonged exposure (92 hr) to tetradecanol produced even higher tissue concentrations (0.7 mmol per kg wet weight), yet no anesthetic effects were observed. Furthermore, general anesthetics are thought to act on postsynaptic membranes but both alkanols partitioned into postsynaptic membranes from Torpedo electroplaques. The spin label, 12-doxyl stearate, was incorporated into these membranes. The lipid order parameter it reported was decreased by the anesthetic alcohols (octanol, decanol, and dodecanol), whereas the nonanesthetic alcohols either did not change it significantly (tetradecanol) or actually increased it (hexadecanol and octadecanol). Thus, although lipid solubility is unable to account for the pharmacology of the cut-off in potency of the long-chain alcohols, lipid perturbations provide an accurate description.