Marin P, Quignard J F, Lafon-Cazal M, Bockaert J
Centre CNRS-INSERM de Pharmacologie-Endocrinologie, Montpellier, France.
Neuropharmacology. 1993 Jan;32(1):29-36. doi: 10.1016/0028-3908(93)90126-n.
In striatal neurons in primary culture, kainate and domoate stimulated cGMP production, whereas two other analogs of glutamate which act at non-NMDA receptors, alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) and quisqualate were ineffective. However, both agonists stimulated cGMP accumulation on neurons pretreated with concanavalin A, a lectin which is known to prevent desensitization of AMPA receptors. We show here that such a treatment also potentiated the kainate-stimulated cGMP production. Responses induced by all agonists of non-NMDA receptors tested were mediated by nitric oxide (NO) production, since they were inhibited by haemoglobin, an NO scavenger, and two competitive inhibitors of NO-synthase L-NG-monomethylarginine and L-NG-nitro-arginine, the effects of both inhibitors being reversed by an excess of L-arginine. The rank order of potency of the agonists tested (domoate > kainate approximately AMPA approximately quisqualate) suggests that a kainate receptor subtype triggers NO production in striatal neurons. Surprisingly, response evoked by maximally effective concentrations of kainate, quisqualate and AMPA on concanavalin A-treated neurons were partially antagonized by two non-competitive antagonists of NMDA receptors, MK-801 and phencyclidine, and by Mg2+ ions, which block NMDA-operated channels. However, in neurons which had not been treated with concanavalin A, kainate-induced NO production was not inhibited by these antagonists. These results suggest that, in addition to kainate receptor subtype, another glutamate receptor subtype which may be composed of both kainate and NMDA receptor subunits and which is desensitized by kainate, AMPA and quisqualate, is involved in NO production.
在原代培养的纹状体神经元中，海人酸和软骨藻酸可刺激环磷酸鸟苷（cGMP）的产生，而另外两种作用于非NMDA受体的谷氨酸类似物，即α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）和喹啉酸则无此作用。然而，这两种激动剂均可刺激经伴刀豆球蛋白A预处理的神经元中cGMP的积累，伴刀豆球蛋白A是一种已知可防止AMPA受体脱敏的凝集素。我们在此表明，这种处理还增强了海人酸刺激的cGMP产生。所测试的所有非NMDA受体激动剂诱导的反应均由一氧化氮（NO）的产生介导，因为它们被血红蛋白（一种NO清除剂）以及两种NO合酶竞争性抑制剂L-NG-单甲基精氨酸和L-NG-硝基精氨酸所抑制，两种抑制剂的作用均可被过量的L-精氨酸逆转。所测试激动剂的效力顺序（软骨藻酸>海人酸≈AMPA≈喹啉酸）表明，一种海人酸受体亚型可触发纹状体神经元中NO的产生。令人惊讶的是，最大有效浓度的海人酸、喹啉酸和AMPA对伴刀豆球蛋白A处理的神经元所诱发的反应，被两种NMDA受体非竞争性拮抗剂MK-801和苯环利定以及阻断NMDA操纵通道的Mg2+离子部分拮抗。然而，在未用伴刀豆球蛋白A处理的神经元中，海人酸诱导的NO产生不受这些拮抗剂的抑制。这些结果表明，除了海人酸受体亚型外，另一种谷氨酸受体亚型可能由海人酸和NMDA受体亚基组成，并且会被海人酸、AMPA和喹啉酸脱敏，它也参与了NO的产生。
