D-serine is an endogenous ligand for the glycine site of the N-methyl-D-aspartate receptor
D-serine is an endogenous ligand for the glycine site of the N-methyl-D-aspartate receptor
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DOI：
10.1073/pnas.97.9.4926
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发表时间：
2000-04-25
影响因子：
11.1
通讯作者：
Snyder, SH
中科院分区：
文献类型：
--
作者：
Mothet, JP;Parent, AT;Snyder, SH
N-甲基-D-天冬氨酸（NMDA）受体的功能活性需要谷氨酸结合和被认为是甘氨酸的内源性促凝剂的结合，尽管D-丝氨酸是更有效的激动剂。D-丝氨酸及其生物合成酶丝氨酸消旋酶的定位比甘氨酸更接近NMDA受体的分布，我们现在表明，用D-氨基酸氧化酶选择性降解D-丝氨酸大大减弱了NMDA受体介导的神经传递，这是通过使用全细胞膜片钳记录或间接使用NMDA受体后遗症的生化测定来评估的。介导的钙流。酶的抑制作用完全逆转外源性应用的D-丝氨酸，这本身并没有加强NMDA受体介导的突触反应。因此，D-丝氨酸是NMDA受体甘氨酸位点的内源性调节剂，并在某些功能性突触中完全占据该位点。
Functional activity of N-methyl-D-aspartate (NMDA) receptors requires both glutamate binding and the binding of an endogenous coagonist that has been presumed to be glycine, although D-serine is a more potent agonist, Localizations of D-serine and it biosynthetic enzyme serine racemase approximate the distribution of NMDA receptors more closely than glycine, We now show that selective degradation of D-serine with D-amino acid oxidase greatly attenuates NMDA receptor-mediated neurotransmission as assessed by using whole-cell patch-clamp recordings or indirectly by using biochemical assays of the sequelae of NMDA receptor-mediated calcium flux. The inhibitory effects of the enzyme are fully reversed by exogenously applied D-serine, which by itself did not potentiate NMDA receptor-mediated synaptic responses. Thus, D-serine is an endogenous modulator of the glycine site of NMDA receptors and fully occupies this site at some functional synapses.