NMDA RECEPTORS ACTIVATE THE ARACHIDONIC-ACID CASCADE SYSTEM IN STRIATAL NEURONS
NMDA RECEPTORS ACTIVATE THE ARACHIDONIC-ACID CASCADE SYSTEM IN STRIATAL NEURONS
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DOI：
10.1038/336068a0
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发表时间：
1988-11-03
期刊：
影响因子：
64.8
通讯作者：
BOCKAERT, J
中科院分区：
文献类型：
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作者：
DUMUIS, A;SEBBEN, M;BOCKAERT, J
神经细胞上的兴奋性氨基酸递质受体分为两大类，与非选择性阳离子通道相关，即NMDA （n-甲基- d -天冬氨酸）和非NMDA（盐酸盐和准盐酸盐）受体1,2。NMDA受体的特殊性质，如Mg2+的电压依赖性阻断（文献3,4）以及它们对Na+， K+和Ca2+的渗透性（文献5,6），导致这些受体在发育和学习期间的可塑性中起重要作用。它们与长期增强作用（LTP）有关，LTP是研究学习细胞机制的一种模型。我们在这里报道，谷氨酸和NMDA，作用于典型的NMDA受体，刺激释放花生四烯酸(以及11-和12-羟基二碳四烯酸从纹状体神经元可能是通过刺激Ca2+依赖性磷脂酶A2。Kainate和quisqualate以及K+诱导的去极化无效。我们的研究结果提供了支持假设12,13的直接证据，即由突触后细胞激活产生的花生四烯酸衍生物可能是穿越突触间隙的信使，以改变已知在LTP9期间改变的突触前功能。此外，我们认为NMDA受体是突触后受体，它触发这些假定的跨突触信使的合成。
Receptors for excitatory amino-acid transmitters on nerve cells fall into two main categories associated with non-selective cationic channels, the NMDA (N-methyl-D-aspartate) and non-NMDA (kainate and quisqualate) receptors1,2. Special properties of NMDA receptors such as their voltage-dependent blockade by Mg2+(refs 3,4) and their permeability to Na+, K+as well as to Ca2+(refs 5,6), have led to the suggestion that these receptors are important in plasticity during development and learning. They have been implicated in long-term potentiation7(LTP), a model for the study of the cellular mechanisms of learning7–11. We report here that glutamate and NMDA, acting at typical NMDA receptors, stimulate the release of arachidonic acid (as well as 11- and 12-hydroxyeicosatetraenoic acids from striatal neurons probably by stimulation of a Ca2+-dependent phospholipase A2. Kainate and quisqualate, as well as K+-induced depolarization were ineffective. Our results provide direct evidence in favour of the hypothesis12,13, that arachidonic acid derivatives, produced by activation of the postsynaptic cell, could be messengers that cross the synaptic cleft to modify the presynaptic functions known to be altered during LTP9. In addition, we suggest that NMDA receptors are the postsynaptic receptors which trigger the synthesis of these putative transynaptic messengers.