Tao Yuan-Xiang, Johns Roger A
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Mol Interv. 2004 Aug;4(4):215-21. doi: 10.1124/mi.4.4.5.
Despite widespread use of volatile general anesthetics in millions of patients each year, the mechanisms by which they exert multiple effects on the behavior of central neurons are poorly understood. PDZ [postsynaptic density 95 (PSD-95), discs large (Dlg), and zonula occludens-1 (ZO-1)] domains are ubiquitous protein interaction modules that participate in neuronal signaling. Recent studies have indicated that clinically relevant concentrations of inhaled anesthetics dose-dependently and specifically inhibit the PDZ domain-mediated protein interactions among multiprotein signaling complexes. These inhibitory effects are immediate, potent, reversible, and occur at a hydrophobic peptidebinding groove on the surface of the PDZ domain. Thus, the PDZ domain might be a new molecular target for inhalational anesthetics.
尽管每年有数百万患者广泛使用挥发性全身麻醉药，但其对中枢神经元行为产生多种作用的机制仍知之甚少。PDZ[突触后致密蛋白95（PSD-95）、盘状大蛋白（Dlg）和紧密连接蛋白1（ZO-1）]结构域是普遍存在的蛋白质相互作用模块，参与神经元信号传导。最近的研究表明，临床相关浓度的吸入麻醉药以剂量依赖且特异性的方式抑制多蛋白信号复合物之间PDZ结构域介导的蛋白质相互作用。这些抑制作用迅速、强效、可逆，且发生在PDZ结构域表面的一个疏水性肽结合凹槽处。因此，PDZ结构域可能是吸入麻醉药的一个新的分子靶点。
