Department of Pharmacology, Emory University School of Medicine, Rollins Research Center, 1510 Clifton Road, Atlanta, GA 30322-3090, USA.
Pharmacol Rev. 2010 Sep;62(3):405-96. doi: 10.1124/pr.109.002451.
The mammalian ionotropic glutamate receptor family encodes 18 gene products that coassemble to form ligand-gated ion channels containing an agonist recognition site, a transmembrane ion permeation pathway, and gating elements that couple agonist-induced conformational changes to the opening or closing of the permeation pore. Glutamate receptors mediate fast excitatory synaptic transmission in the central nervous system and are localized on neuronal and non-neuronal cells. These receptors regulate a broad spectrum of processes in the brain, spinal cord, retina, and peripheral nervous system. Glutamate receptors are postulated to play important roles in numerous neurological diseases and have attracted intense scrutiny. The description of glutamate receptor structure, including its transmembrane elements, reveals a complex assembly of multiple semiautonomous extracellular domains linked to a pore-forming element with striking resemblance to an inverted potassium channel. In this review we discuss International Union of Basic and Clinical Pharmacology glutamate receptor nomenclature, structure, assembly, accessory subunits, interacting proteins, gene expression and translation, post-translational modifications, agonist and antagonist pharmacology, allosteric modulation, mechanisms of gating and permeation, roles in normal physiological function, as well as the potential therapeutic use of pharmacological agents acting at glutamate receptors.
哺乳动物离子型谷氨酸受体家族编码 18 种基因产物，这些基因产物共同组装形成配体门控离子通道，其中包含激动剂识别位点、跨膜离子渗透途径和门控元件，这些元件将激动剂诱导的构象变化与渗透孔的打开或关闭偶联。谷氨酸受体介导中枢神经系统中的快速兴奋性突触传递，位于神经元和非神经元细胞上。这些受体调节大脑、脊髓、视网膜和周围神经系统中的广泛过程。谷氨酸受体被认为在许多神经疾病中发挥重要作用，引起了广泛关注。谷氨酸受体结构的描述，包括其跨膜元件，揭示了多个半自主的细胞外结构域与一个形成孔的元件的复杂组装，该元件与倒置的钾通道具有惊人的相似性。在这篇综述中，我们讨论了国际药理学联合会的谷氨酸受体命名法、结构、组装、辅助亚基、相互作用蛋白、基因表达和翻译、翻译后修饰、激动剂和拮抗剂药理学、变构调节、门控和渗透机制、在正常生理功能中的作用，以及作用于谷氨酸受体的药物在治疗中的潜在应用。
