A hippocampal GluR5 kainate receptor regulating inhibitory synaptic transmission
A hippocampal GluR5 kainate receptor regulating inhibitory synaptic transmission
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DOI：
10.1038/39315
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发表时间：
1997-10-09
期刊：
影响因子：
64.8
通讯作者：
Bleakman, D
中科院分区：
文献类型：
--
作者：
Clarke, VRJ;Ballyk, BA;Bleakman, D
脊椎动物中枢神经系统中的主要兴奋性神经递质L-谷氨酸作用于三类亲离子谷氨酸受体，以激动剂AMPA（α-氨基-3-羟基-5-甲基-4-异戊烯-4-丙酸）、NMDA（N-甲基-D-天冬氨酸）和红藻氨酸命名（1）。选择性药理学试剂的开发已经导致对AMPA和NMDA受体的生理和病理作用的详细理解（2-8）。相反，选择性红藻氨酸受体配体的缺乏极大地阻碍了理解红藻氨酸受体作用的进展（9，10）。在这里，我们描述了一种有效的和选择性的激动剂，ATPA（（RS）-2-氨基-3-氨基-2-氨基-3-氨基-3-氨基-2-氨基-2-氨基-3-氨基-3-氨基-2-氨基-2-氨基-3-氨基-2-氨基-2-（3-羟基-5-叔丁基异恶唑-4-基）丙酸）和选择性拮抗剂LY 294486（（3SR，4aRS，6SR，8aRS）-6-（1H-四唑-5-基）甲基）氧基）甲基）-1，2，3，4，4a，5，6，7，8，8a-十氢异喹啉-3-羧酸），红藻氨酸受体的GluR 5亚型（11）。我们已经使用这些药物来表明，由GluR 5亚基组成或含有GluR 5亚基的红藻氨酸受体调节海马中的突触抑制，这一作用可能有助于红藻氨酸的致癫痫作用（12-17）。
The principal excitatory neurotransmitter in the vertebrate central nervous system, L-glutamate, acts on three classes of ionotripic glutamate receptors, named after the agonists AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxalole-4-propionic acid),NMDA (N-methyl-D-aspartate) and kainate(1). The development of selective pharmacological agents has led to a detailed understanding of the physiological and pathological roles of AMPA and NMDA receptors(2-8). in contrast, the lack of selective kainate receptor ligands has greatly hindered progress in understanding the roles of kainate receptors(9,10). Here we describe the effects of a potent and selective agonist, ATPA ((RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid) and a selective antagonist, LY294486 ((3SR, 4aRS, 6SR, 8aRS)-6-((((1H-tetrazol-5-yl) methyl)oxy)methyl)-1, 2, 3, 4, 4a, 5, 6, 7, 8, 8a-decahydroisoquinoline-3-carboxylic acid), of the GluR5 subtype of kainate receptor(11). We have used these agents to show that kainate receptors, comprised of or containing GluR5 subunits, regulate synaptic inhibition in the hippocampus, an action that could contribute to the epileptogenic effects of kainate(12-17).