Simeone Timothy A, Sanchez Russell M, Rho Jong M
Department of Pediatrics, University of California at Irvine College of Medicine, Irvine, CA, USA.
J Child Neurol. 2004 May;19(5):343-60; discussion 361. doi: 10.1177/088307380401900507.
Glutamate is the principal excitatory neurotransmitter in the mammalian central nervous system. After release from presynaptic terminals, glutamate binds to both ionotropic and metabotropic receptors to mediate fast, slow, and persistent effects on synaptic transmission and integrity. There are three types of ionotropic glutamate receptors. N-Methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA), and kainate receptors are principally activated by the agonist bearing its name and are permeable to cationic flux; hence, their activation results in membrane depolarization. All ionotropic glutamate receptors are believed to be composed of four distinct subunits, each of which is topologically arranged with three transmembrane-spanning and one pore-lining (hairpin loop) domain. In contrast, metabotropic glutamate receptors are G protein (guanine nucleotide-binding protein) -coupled receptors linked to second-messenger systems. Group I metabotropic glutamate receptors are linked to phospholipase C, which results in phosphoinositide hydrolysis and release of calcium from intracellular stores. Group II and group III metabotropic glutamate receptors are negatively linked to adenylate cyclase, which catalyzes the production of cyclic adenosine monophosphate. Each metabotropic glutamate receptor is composed of seven transmembrane-spanning domains, similar to other members of the superfamily of metabotropic receptors, which includes noradrenergic, muscarinic acetylcholinergic, dopaminergic, serotonergic (except type 3 receptors), and gamma-aminobutyric acid (GABA) type B receptors. This review summarizes the relevant molecular biology and ontogeny of glutamate receptors in the central nervous system and highlights some of the roles that they can play during brain development and in certain disease states.
谷氨酸是哺乳动物中枢神经系统中的主要兴奋性神经递质。从突触前终末释放后，谷氨酸与离子型和代谢型受体结合，介导对突触传递和完整性的快速、缓慢及持久影响。离子型谷氨酸受体有三种类型。N-甲基-D-天冬氨酸（NMDA）、α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）和海人藻酸受体主要由与其名称相同的激动剂激活，并对阳离子通量具有通透性；因此，它们的激活会导致膜去极化。所有离子型谷氨酸受体被认为由四个不同的亚基组成，每个亚基在拓扑结构上都有三个跨膜结构域和一个孔道内衬（发夹环）结构域。相比之下，代谢型谷氨酸受体是与第二信使系统相连的G蛋白（鸟嘌呤核苷酸结合蛋白）偶联受体。I组代谢型谷氨酸受体与磷脂酶C相连，导致磷酸肌醇水解并从细胞内储存中释放钙。II组和III组代谢型谷氨酸受体与腺苷酸环化酶负性相连，腺苷酸环化酶催化环磷酸腺苷的产生。每个代谢型谷氨酸受体由七个跨膜结构域组成，类似于代谢型受体超家族的其他成员，该超家族包括去甲肾上腺素能、毒蕈碱型乙酰胆碱能、多巴胺能、5-羟色胺能（3型受体除外）和γ-氨基丁酸（GABA）B型受体。本文综述了中枢神经系统中谷氨酸受体的相关分子生物学和个体发生，并强调了它们在脑发育和某些疾病状态下可能发挥的一些作用。
