Effect of the NR3 subunit on ethanol inhibition of recombinant NMDA receptors.
Effect of the NR3 subunit on ethanol inhibition of recombinant NMDA receptors.
复制标题
NR3 亚基对重组 NMDA 受体乙醇抑制的影响。
DOI：
10.1016/s0006-8993(03)03315-8
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发表时间：
2003
期刊：
影响因子：
2.9
通讯作者：
Woodward,JohnJ
中科院分区：
文献类型：
--
作者：
Smothers,CThetford;Woodward,JohnJ
n -甲基-d-天冬氨酸（NMDA）受体是谷氨酸受体的一个亚型，在大脑的谷氨酸能突触中起重要作用。NMDA受体受到乙醇浓度的抑制，这与中毒和慢性暴露于乙醇的神经元增强NMDA受体功能有关。乙醇对NMDA受体的急性抑制的潜在因素尚不完全清楚，但乙醇敏感性受到受体亚基组成的影响。本研究考察了调控亚基NR3对乙醇对NMDA受体的抑制作用。在NR3亚基缺失或存在的情况下，将NR1和NR2 （A-D）亚基组成的重组NMDA受体瞬时转染到HEK293细胞中。在NR3缺失的情况下，所有NMDA受体亚基组合均被100 mM乙醇抑制。NR3或NR3- gfp融合蛋白与NR1/NR2 （A-D）亚基的共表达并未改变乙醇的抑制作用。此外，NR2B亚基选择性拮抗剂伊芬普罗地尔对NR1/NR2B受体的抑制作用不会因NR3亚基的共表达而改变。总之，这些结果表明NR3A亚基不是重组NMDA受体中乙醇敏感性的决定因素。
N-Methyl-d-aspartate (NMDA) receptors are a subtype of glutamate receptor that serve important functions at glutamatergic synapses in the brain. NMDA receptors are inhibited by concentrations of ethanol that are associated with intoxication and chronic exposure of neurons to ethanol enhances NMDA receptor function. The factors that underlie the acute inhibition of NMDA receptors by ethanol are not completely known, but ethanol sensitivity is influenced by receptor subunit composition. In this study, the effect of the regulatory subunit, NR3, on ethanol inhibition of NMDA receptors was examined. Recombinant NMDA receptors comprised of NR1 and NR2 (A–D) subunits were transiently transfected into HEK293 cells in the absence or presence of the NR3 subunit. In the absence of NR3, all NMDA receptor subunit combinations were inhibited by 100 mM ethanol. Co-expression of NR3 or an NR3-GFP fusion protein with NR1/NR2 (A–D) subunits did not alter the inhibitory effects of ethanol. In addition, the inhibition of NR1/NR2B receptors by the NR2B subunit-selective antagonist, ifenprodil, was not altered by co-expression of the NR3 subunit. Overall, these results suggest that the NR3A subunit is not a determinant of ethanol sensitivity in recombinant NMDA receptors.