Tas P W, Kress H G, Koschel K
Proc Natl Acad Sci U S A. 1987 Aug;84(16):5972-5. doi: 10.1073/pnas.84.16.5972.
It is not known whether proteins or lipids are the primary target of anesthetic action. The resolution of this problem is hampered by the fact that it is not possible to investigate the biological activity of integral membrane proteins in the absence of lipids. However, certain characteristics of membrane protein function inhibition by anesthetics cannot be explained on the basis of an indirect inhibition by disturbance of the lipid bilayer and, therefore, most likely are the result of a direct anesthetic-protein interaction. This is the case (i) when the anesthetics competitively interfere with the binding of an endogenous ligand to the membrane protein and (ii) when the size of the anesthetic molecule is of importance for the potency and/or mechanism of inhibition. The present study shows that this is true for a membrane transport system, the Na+/K+/Cl- cotransport in glial-type cells.
目前尚不清楚蛋白质或脂质是否是麻醉作用的主要靶点。由于在没有脂质的情况下无法研究整合膜蛋白的生物活性，这一问题的解决受到了阻碍。然而，麻醉剂对膜蛋白功能的抑制的某些特征无法基于脂质双分子层紊乱的间接抑制来解释，因此，很可能是麻醉剂与蛋白质直接相互作用的结果。当麻醉剂竞争性地干扰内源性配体与膜蛋白的结合时，以及当麻醉剂分子的大小对抑制效力和/或机制很重要时，就是这种情况。本研究表明，对于一种膜转运系统，即胶质细胞类型中的Na+/K+/Cl-协同转运，情况确实如此。
