[3H]CGP 39653 binding to the agonist site of the N-methyl-D-aspartate receptor is modulated by Mg2+ and polyamines independently of the arcaine-sensitive polyamine site.
[3H]CGP 39653 binding to the agonist site of the N-methyl-D-aspartate receptor is modulated by Mg2+ and polyamines independently of the arcaine-sensitive polyamine site.
复制标题
[3H]CGP 39653 与 N-甲基-D-天冬氨酸受体激动剂位点的结合受到 Mg2 和多胺的调节，独立于阿卡因敏感的多胺位点。
DOI：
10.1046/j.1471-4159.1994.62010054.x
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发表时间：
1994
影响因子：
4.7
通讯作者：
Reynolds,IJ
中科院分区：
文献类型：
--
作者：
Reynolds,IJ
This study investigated the binding of [3H] CGP 39653, a novel high‐affinity antagonist of theN‐methyl‐D‐ aspartate (NMDA) recognition site of the NMDA receptor complex. [3H] CGP 39653 bound to the NMDA receptor in well washed rat brain membranes with an affinity of about 15 nM.Other NMDA site drugs inhibited [3H] CGP 39653 binding with the following order of potency: DL‐(tetrazol‐5‐ yl)glycine > glutamate > CGS 19755 > DL‐2‐amino‐5‐ phosphonovalerate (DL‐AP5) > NMDA. Glycine and 5, 7‐ dichlorokynurenate partially inhibited binding. The poly‐amines spermine and spermidine increased [3H] CGP 39653 binding (EC50values of 10 and 22 μM, respectively). This effect was mimicked by arcaine, 1, 5‐diethylaminopiperidine, diaminodecane, diethylenetriamine, and Mg2+. The increase in [3H] CGP 39653 was a result of an increased affinity of the binding site for the ligand with very little effect on binding site density. Spermine and Mg2+also increased the affinity of the antagonists DL‐AP5 and CGS 19755, but had only minor effects on the affinity of glutamate and NMDA. Arcaine did not reverse the enhancement of [3H] CGP 39653 binding by spermine, spermidine, or Mg2+. Channel‐blocking dissociative anesthetics, including dizocilpine and ketamine, did not alter basal or Mg2+‐stimulated [3H] CGP 39653 binding. Spermine did not alter either the enhancement of [3H]‐ dizocilpine by glutamate or the inhibition of [3H]dizocilpine by DL‐AP5 or CGS 19755. These studies show that poly‐amines and divalent cations selectively enhance the affinity of antagonists for the agonist binding site on the NMDA receptor complex. However, this effect is mediated by a site independent of the primary polyamine site defined using [3H] dizocilpine binding.
