D-SERINE, AN ENDOGENOUS SYNAPTIC MODULATOR - LOCALIZATION TO ASTROCYTES AND GLUTAMATE-STIMULATED RELEASE
D-SERINE, AN ENDOGENOUS SYNAPTIC MODULATOR - LOCALIZATION TO ASTROCYTES AND GLUTAMATE-STIMULATED RELEASE
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DOI：
10.1073/pnas.92.9.3948
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发表时间：
1995-04-25
影响因子：
11.1
通讯作者：
SNYDER, SH
中科院分区：
文献类型：
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作者：
SCHELL, MJ;MOLLIVER, ME;SNYDER, SH
使用抗体对D-丝氨酸结合戊二醛高度特异性，我们本地化内源性D-丝氨酸在大鼠脑。最高水平的D-丝氨酸免疫反应性发生在大脑皮质、海马、前嗅核、嗅结节和杏仁核的灰质中。D-丝氨酸免疫反应性的定位与通过放射自显影观察到的D-丝氨酸结合到N-甲基-D-天冬氨酸（NMDA）受体的甘氨酸调节位点的定位密切相关，并且与D-氨基酸氧化酶的存在负相关，D-丝氨酸在神经胶质细胞中富集，具有原生质星形胶质细胞的形态。在大鼠大脑皮层的胶质细胞培养物中，D-丝氨酸在2型星形胶质细胞中富集。从这些培养物中释放的D-丝氨酸被非NMDA谷氨酸受体的激动剂刺激，表明星形胶质细胞衍生的D-丝氨酸可以调节神经传递的机制。D-丝氨酸似乎是NMDA受体甘氨酸位点的内源性配体。
Using an antibody highly specific for D-serine conjugated to glutaraldehyde, we have localized endogenous D-serine in rat brain. Highest levels of D-serine immunoreactivity occur in the gray matter of the cerebral cortex, hippocampus, anterior olfactory nucleus, olfactory tubercle, and amygdala, Localizations of D-serine immunoreactivity correlate closely with those of D-serine binding to the glycine modulatory site of the N-methyl-D-aspartate (NMDA) receptor as visualized by autoradiography and are inversely correlated to the presence of D-amino acid oxidase, D-Serine is enriched in process-bearing glial cells in neuropil with the morphology of protoplasmic astrocytes. In glial cultures of rat cerebral cortex, D-serine is enriched in type 2 astrocytes. The release of D-serine from these cultures is stimulated by agonists of non-NMDA glutamate receptors, suggesting a mechanism by which astrocyte-derived D-serine could modulate neurotransmission. D-Serine appears to be the endogenous ligand for the glycine site of NMDA receptors.