Magazanik L G, Usherwood P N
Laboratory of Biophysics, Russian Academy of Sciences, St Petersburg, Russia.
Neuroreport. 1996 Dec 20;8(1):257-9. doi: 10.1097/00001756-199612200-00051.
The classical division of mammalian ionotropic L-glutamate (Glu) receptors into N-methyl-D-aspartate (NMDA) and non-NMDA classes is supported by a wealth of biochemical and molecular biological data. In binding studies, selective agonists for non-NMDA receptors such as L-kainate (KA), alpha-amino-3-hydroxy-5-methylisoxazole-propionate (AMPA) and L-domoate have submicromolar affinities; in contrast, a millimolar concentration of NMDA is required significantly to compete with the non-NMDA agonists. Despite the supposed clear-cut selectivities of these amino acids, interactions between the responses to submillimolar concentrations of NMDA and KA have been observed in cells expressing both classes of Glu receptor. We present here evidence that NMDA is a competitive antagonist of recombinant non-NMDA receptors. We also present preliminary data on competitive antagonism of recombinant NMDA receptors by KA. These antagonisms are inhibited non-competitively by cyclothiazide and a benzodiazipine.
哺乳动物离子型L-谷氨酸（Glu）受体经典地分为N-甲基-D-天冬氨酸（NMDA）和非NMDA两类，这得到了大量生物化学和分子生物学数据的支持。在结合研究中，非NMDA受体的选择性激动剂，如L-海人酸（KA）、α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）和L-软骨藻酸，具有亚微摩尔亲和力；相比之下，需要毫摩尔浓度的NMDA才能与非NMDA激动剂进行有效竞争。尽管这些氨基酸具有明显的选择性，但在同时表达两类Glu受体的细胞中，已观察到亚毫摩尔浓度的NMDA和KA之间的反应存在相互作用。我们在此提供证据表明，NMDA是重组非NMDA受体的竞争性拮抗剂。我们还提供了KA对重组NMDA受体竞争性拮抗作用的初步数据。这些拮抗作用可被环噻嗪和一种苯二氮䓬非竞争性抑制。
