Johnson J W, Ascher P
Nature. 1987;325(6104):529-31. doi: 10.1038/325529a0.
Transmitters mediating 'fast' synaptic processes in the vertebrate central nervous system are commonly placed in two separate categories that are believed to exhibit no interaction at the receptor level. The 'inhibitory transmitters' (such as glycine and GABA) are considered to act only on receptors mediating a chloride conductance increase, whereas 'excitatory transmitters' (such as L-glutamate) are considered to activate receptors mediating a cationic conductance increase. The best known excitatory receptor is that specifically activated by N-methyl-D-aspartate (NMDA) which has recently been characterized at the single channel level. The response activated by NMDA agonists is unique in that it exhibits a voltage-dependent Mg block. We report here that this response exhibits another remarkable property: it is dramatically potentiated by glycine. This potentiation is not mediated by the inhibitory strychnine-sensitive glycine receptor, and is detected at a glycine concentration as low as 10 nM. The potentiation can be observed in outside-out patches as an increase in the frequency of opening of the channels activated by NMDA agonists. Thus, in addition to its role as an inhibitory transmitter, glycine may facilitate excitatory transmission in the brain through an allosteric activation of the NMDA receptor.
在脊椎动物中枢神经系统中，介导“快速”突触过程的递质通常分为两类，人们认为这两类递质在受体水平上不存在相互作用。“抑制性递质”（如甘氨酸和γ-氨基丁酸）被认为仅作用于介导氯离子电导增加的受体，而“兴奋性递质”（如L-谷氨酸）则被认为激活介导阳离子电导增加的受体。最著名的兴奋性受体是由N-甲基-D-天冬氨酸（NMDA）特异性激活的受体，最近已在单通道水平对其进行了表征。NMDA激动剂激活的反应具有独特之处，即它表现出电压依赖性镁离子阻滞。我们在此报告，这种反应还具有另一个显著特性：它会被甘氨酸显著增强。这种增强作用不是由对士的宁敏感的抑制性甘氨酸受体介导的，在低至10 nM的甘氨酸浓度下即可检测到。这种增强作用在外翻膜片中表现为NMDA激动剂激活的通道开放频率增加。因此，除了作为抑制性递质的作用外，甘氨酸可能通过对NMDA受体的变构激活来促进大脑中的兴奋性传递。
