Competitive antagonism of glycine at the N-methyl-D-aspartate (NMDA) receptor.
Competitive antagonism of glycine at the N-methyl-D-aspartate (NMDA) receptor.
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DOI：
10.1016/0006-2952(91)90004-o
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发表时间：
1991
影响因子：
5.8
通讯作者：
J. E. Huettner
中科院分区：
文献类型：
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作者：
J. E. Huettner
N-甲基-D-天冬氨酸(NMDA)在七十年代末被认为是谷氨酸受体一种不同亚型的选择性激动剂(见参考文献)。1个供审查)。NMDA或谷氨酸的结合控制着对钙离子和一价阳离子具有通透性的离子通道的门控[2-6]；细胞外镁离子的生理浓度以电压依赖的方式阻断该通道[6]。1987年，Johnson和Ascher[7]发现，甘氨酸是细胞外液的另一种正常成分，对NMDA受体起着强大的正向调节作用。激活NMDA通道导致去极化，进入的钙被认为是调节兴奋性突触强度和稳定性的内部信使[8-101]。在过度兴奋期间，兴奋性细胞死亡[11-14]与癫痫、缺血和几种神经退行性疾病有关。因此，NMDA受体功能拮抗剂可能在临床上用于治疗这些疾病，并已成为人们强烈兴趣的主题[15，16]。由于其复杂性，N-甲基-D-天冬氨酸受体提供了几个可能的化学干预靶点，包括谷氨酸或N-甲基-D-天冬氨酸结合位点[L，171，离子通道[LS]和甘氨酸调节位点。本文综述了近年来甘氨酸调节的药理学研究进展。
N-Methyl-D-aspartate (NMDA) was recognized in the late seventies as a selective agonist for a distinct subtype of glutamate receptor (see Ref. 1 for review). Binding of NMDA or glutamate controls the gating of ion channels that are permeable to calcium and monovalent cations [2-6]; physiological concentrations of extracellular Mg2+ block the channel in a voltage-dependent manner [6]. In 1987, Johnson and Ascher [7] discovered that glycine, another normal constituent of extracellular fluid, acts as a powerful positive modulator of NMDA receptors. Activation of the NMDA channel leads to depolarization and the calcium that enters is thought to serve as an internal messenger to regulate the strength and stability of excitatory synapses [8-101.Excessive calcium entry. during periods of hyperexcitation has been implicated in excitotoxic cell death [ll-14) associated with epilepsy, ischemia and several neurodegenerative conditions. For this reason, antagonists of NMDA receptor function may be clinically useful in the treatment of these disorders and have become the subject of intense interest [15, 16]. Because of its complexity, the NMDA receptor provides several possible targets for chemical intervention including the glutamate or NMDA binding site [l, 171, the ion channel [lS) and the glycine modulation site. This paper considers recent work on the pharmacology of glycine modulation.