Davies J, Miller A J, Sheardown M J
J Physiol. 1986 Jul;376:13-29. doi: 10.1113/jphysiol.1986.sp016139.
A study has been made of the effects of the selective N-methyl-D-aspartate receptor antagonist, 2-amino-5-phosphonovalerate (APV), and the broad spectrum excitatory amino acid antagonists, gamma-D-glutamylglycine (gamma-DGG), gamma-D-glutamylaminomethylsulphonate (GAMS), 4(p-chlorobenzoyl)-cis-piperazine-2, 3-dicarboxylate (pCB-PzDA) and kynurenate, have been examined on excitation evoked on neurones in the magnocellular red nucleus (m.r.n.) of the anaesthetized cat by stimulation of the interpositus nucleus (i.p.n.) and sensorimotor cortex, and by ionophoresed excitant amino acid agonists. The profile of activity of the excitatory amino acid antagonists on m.r.n. neurones was similar to that described on neurones in other areas of the central nervous system. APV selectively depressed responses to N-methyl-D-aspartate (NMDA), whereas the broader spectrum antagonists reduced responses to kainate and quisqualate as well as to NMDA. Neuronal responses to L-glutamate and L-aspartate were depressed by all the antagonists tested. I.p.n.-evoked monosynaptic responses of m.r.n. neurones were reversibly reduced by the broad spectrum antagonists, but were unaffected by APV. Cortically evoked mono- and polysynaptic excitatory responses were reversibly depressed by APV and the broad spectrum antagonist, pCB-PzDA. The action of APV corresponded with its ability to antagonize responses to NMDA. However, the cortically evoked responses appeared to be more sensitive to the actions of pCB-PzDA than to those of APV, although the former is a less effective antagonist of NMDA-induced excitation compared with APV. APV depressed excitation induced by cortical stimuli and L-glutamate and L-aspartate. However, there was no obvious correlation between the actions of the broad spectrum amino acid antagonists on synaptically evoked responses and those induced by L-glutamate or L-aspartate on the few neurones tested. These results are consistent with an amino acid being the transmitter in the interposito-rubral and cortico-rubral excitatory pathways which interacts with non-NMDA and both NMDA and non-NMDA receptors respectively. However, the identity of the transmitter acting at these receptors remains to be determined.
研究了选择性N-甲基-D-天冬氨酸受体拮抗剂2-氨基-5-磷酸戊酸(APV)以及广谱兴奋性氨基酸拮抗剂γ-D-谷氨酰甘氨酸(γ-DGG)、γ-D-谷氨酰氨基甲基磺酸盐(GAMS)、4-(对氯苯甲酰基)-顺式哌嗪-2,3-二羧酸盐(pCB-PzDA)和犬尿烯酸对麻醉猫大细胞红核(m.r.n.)神经元兴奋的影响,这些兴奋是通过刺激间位核(i.p.n.)和感觉运动皮层以及通过离子导入兴奋性氨基酸激动剂诱发的。兴奋性氨基酸拮抗剂对m.r.n.神经元的活性特征与在中枢神经系统其他区域神经元上所描述的相似。APV选择性地抑制对N-甲基-D-天冬氨酸(NMDA)的反应,而广谱拮抗剂则降低对海人藻酸和quisqualate以及对NMDA的反应。所测试的所有拮抗剂都能抑制神经元对L-谷氨酸和L-天冬氨酸的反应。广谱拮抗剂可使i.p.n.诱发的m.r.n.神经元单突触反应可逆性降低,但APV对此无影响。APV和广谱拮抗剂pCB-PzDA可使皮层诱发的单突触和多突触兴奋性反应可逆性降低。APV的作用与其拮抗对NMDA反应的能力相对应。然而,皮层诱发的反应似乎对pCB-PzDA的作用比对APV的作用更敏感,尽管与APV相比,前者对NMDA诱导的兴奋的拮抗作用较弱。APV可抑制皮层刺激以及L-谷氨酸和L-天冬氨酸诱导的兴奋。然而,在少数测试的神经元上,广谱氨基酸拮抗剂对突触诱发反应的作用与L-谷氨酸或L-天冬氨酸诱导的反应之间没有明显的相关性。这些结果与一种氨基酸作为间位核-红核和皮层-红核兴奋性通路中的递质相一致,该递质分别与非NMDA受体以及NMDA和非NMDA受体相互作用。然而,作用于这些受体的递质的身份仍有待确定。