Cazin M, Luyckx M, Brunet C, Meresse C
Laboratoire de Pharmacologie, Pharmacocinétique et Pharmacie Clinique, Faculté de Pharmacie, Lille.
J Pharm Belg. 1991 Mar-Apr;46(2):100-6.
Glutamate, aspartate and possibly other excitatory acidic amino acids are thought to be, neurotransmitters at the majority of excitatory synapses in the vertebrate CSN. The synaptic response elicited by excitatory amino acids is mediated by at least four (probably five) different receptor subtypes. These were known as the N-methyl-D-aspartate, quisqualate, kainate and L-AP4 receptor subtypes. More recently a fifth receptor subtype has been discovered that is linked to phosphoinositol metabolism. The most well characterized excitatory amino acid receptor subtype is the NMDA receptor. This receptor consists of a recognition site for NMDA, a cation-selective ion channel and binding site for glycine, Zn2+ and phencyclidine-like compounds. In addition the channel can be blocked by Mg2+. New and selective ligands and radioligands have facilitated mapping the distribution of the major excitatory receptor subtypes in normal and diseased brain, examines allosteric interactions within the NMDA receptor, searching for novel therapeutic agents and determining drugs mechanisms.
谷氨酸、天冬氨酸以及可能的其他兴奋性酸性氨基酸被认为是脊椎动物中枢神经系统中大多数兴奋性突触的神经递质。兴奋性氨基酸引发的突触反应至少由四种(可能五种)不同的受体亚型介导。这些受体亚型被称为N-甲基-D-天冬氨酸、quisqualate、海人藻酸和L-AP4受体亚型。最近又发现了第五种与磷酸肌醇代谢相关的受体亚型。特征最明确的兴奋性氨基酸受体亚型是NMDA受体。该受体由一个NMDA识别位点、一个阳离子选择性离子通道以及甘氨酸、Zn2+和苯环己哌啶样化合物的结合位点组成。此外,该通道可被Mg2+阻断。新型选择性配体和放射性配体有助于绘制正常和患病大脑中主要兴奋性受体亚型的分布图谱、研究NMDA受体内的变构相互作用、寻找新型治疗药物以及确定药物作用机制。