Trist D G
Glaxo Wellcome Medicines Research Centre, Verona, Italy.
Pharm Acta Helv. 2000 Mar;74(2-3):221-9. doi: 10.1016/s0031-6865(99)00053-9.
Glutamic acid is the major excitatory neurotransmitter in the mammalian central nervous system (CNS). Specific receptors bind glutamate and some of these when activated open an integral ion channel and are thus known as ionotropic receptors. Within the ionotropic family of glutamate receptors, three major subtypes have been identified using classical specific agonist activation, selective competitive antagonists together with their structural heterogeneity. These receptors have thus been named N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and kainate receptors. The NMDA receptor has sites in addition to its agonist-binding site and these seem to either positively or negatively modulate the agonist effect. The NMDA receptor also is unique in that another amino acid, glycine, acts as a co-agonist with glutamate. Changes in glutamate transmission have been associated with a number of CNS pathologies; these include, acute stroke, chronic neurodegeneration, chronic pain, depression, drug dependency, epilepsy, Parkinson's Disease and schizophrenia.
谷氨酸是哺乳动物中枢神经系统（CNS）中的主要兴奋性神经递质。特定受体与谷氨酸结合，其中一些受体在激活时会打开一个完整的离子通道，因此被称为离子型受体。在谷氨酸受体的离子型家族中，通过经典的特异性激动剂激活、选择性竞争性拮抗剂以及它们的结构异质性，已鉴定出三种主要亚型。因此，这些受体被命名为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。NMDA受体除了其激动剂结合位点外还有其他位点，这些位点似乎对激动剂效应有正向或负向调节作用。NMDA受体的独特之处还在于，另一种氨基酸甘氨酸与谷氨酸一起作为共激动剂起作用。谷氨酸传递的变化与多种中枢神经系统疾病有关；这些疾病包括急性中风、慢性神经退行性变、慢性疼痛、抑郁症、药物依赖、癫痫、帕金森病和精神分裂症。
