Minami Kouichiro, Uezono Yasuhito
Department of Anesthesiology, University of Occupational and Environmental Health, Kitakyushu 807-8555.
Masui. 2005 Feb;54(2):118-25.
Although anesthetics have been often used clinically, the mechanisms of action of anesthetics have not yet been clarified. Recently, major advances have been made in our understanding of the physiology and pharmacology of G-protein-coupled receptor (GPCR)-mediated signaling. Several lines of studies have shown that GPCRs are targets for anesthetics and that some anesthetics inhibit the functions of Gq-coupled receptors, including muscarinic acetylcholine (ACh) M1, metabotropic type 5 glutamate, 5-hydroxytryptamine (5-HT) type 2 A, and substance P receptors. Many additional GPCRs have been classified as "orphan" receptors (oGPCRs) because their endogenous ligands have not been identified yet. Given that known GPCRs are targets for anesthetics, these oGPCRs may represent a rich group of receptor targets for anesthetics. This review highlights the effects of anesthetics on Gq-coupled receptors, and discusses whether GPCRs other than Gq-coupled receptors, and proteins that convey GPCR signals are also targets for anesthetics.
尽管麻醉剂已在临床上广泛应用，但其作用机制尚未阐明。近年来，我们对G蛋白偶联受体（GPCR）介导的信号转导的生理学和药理学的理解取得了重大进展。多项研究表明，GPCR是麻醉剂的作用靶点，一些麻醉剂可抑制与Gq偶联的受体的功能，包括毒蕈碱型乙酰胆碱（ACh）M1受体、代谢型5型谷氨酸受体、5-羟色胺（5-HT）2A型受体和P物质受体。许多其他GPCR被归类为“孤儿”受体（oGPCR），因为它们的内源性配体尚未确定。鉴于已知的GPCR是麻醉剂的作用靶点，这些oGPCR可能代表了丰富的麻醉剂受体靶点群体。本文综述强调了麻醉剂对与Gq偶联的受体的影响，并讨论了除与Gq偶联的受体之外的GPCR以及传递GPCR信号的蛋白质是否也是麻醉剂的作用靶点。
