Minami Kouichiro, Uezono Yasuhito
Department of Anesthesiology, University of Occupational and Environmental Health School of Medicine, 1-1 Iseigaoka, Yahatanishiku, Kitakyushu 807-8555, Japan.
Curr Pharm Des. 2006;12(15):1931-7. doi: 10.2174/138161206776873644.
The mechanisms of action of anesthetics are unclear. Much attention has been focused on ion channels in the central nervous system as targets for anesthetics. During the last decade, major advances have been made in our understanding of the physiology and pharmacology of G-protein-coupled receptor (GPCR) 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) M(1), metabotropic type 5 glutamate, 5-hydroxytryptamine (5-HT) type 2A, and substance P receptors. Nearly 160 GPCRs have been identified, based on their gene sequence and ability to interact with known endogenous ligands. However, an estimated 500-800 additional GPCRs have been classified as "orphan" receptors (oGPCRs) because their endogenous ligands have not yet been identified. Given that known GPCRs are targets for anesthetics, these oGPCRs represent a rich group of receptor targets for anesthetics. This article highlights the effects of anesthetics on Gq-coupled receptors, and discusses whether GPCRs other than Gq-coupled receptors are targets for anesthetics.
麻醉药的作用机制尚不清楚。人们将大量注意力集中在中枢神经系统中的离子通道作为麻醉药的作用靶点。在过去十年中，我们对G蛋白偶联受体（GPCR）信号传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是麻醉药的作用靶点，并且一些麻醉药会抑制与Gq偶联的受体的功能，包括毒蕈碱型乙酰胆碱（ACh）M（1）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。基于其基因序列以及与已知内源性配体相互作用的能力，已鉴定出近160种GPCR。然而，估计还有500 - 800种GPCR被归类为“孤儿”受体（oGPCR），因为它们的内源性配体尚未被鉴定出来。鉴于已知的GPCR是麻醉药的作用靶点，这些oGPCR代表了一组丰富的麻醉药受体靶点。本文重点介绍了麻醉药对与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是否也是麻醉药的作用靶点。
