Wake K, Yamazaki H, Hanzawa S, Konno R, Sakio H, Niwa A, Hori Y
Department of Anesthesiology, Dokkyo University School of Medicine, Mibu, 321-0293, Tochigi, Japan.
Neurosci Lett. 2001 Jan 5;297(1):25-8. doi: 10.1016/s0304-3940(00)01658-x.
Formalin-induced nociceptive behaviors and N-methyl-D-aspartate (NMDA) subtype glutamate receptor-mediated excitatory synaptic transmission were analyzed in mutant mice lacking D-amino-acid oxidase, which catalyzes the oxidative deamination of D-amino acids. The second phase of the formalin-induced licking response, a part of which is known to be mediated by NMDA receptors in the spinal cord, was significantly augmented in mutant mice. NMDA receptor-mediated excitatory postsynaptic currents recorded from spinal cord dorsal horn neurons by tight-seal whole-cell methods were significantly potentiated in mutant mice. The present observations provide another line of evidence that D-serine functions as an endogenous coagonist at the glycine site of NMDA receptors, and raise the possibility that D-amino-acid oxidase exerts a neuromodulatory function by controlling the concentration of D-serine in the central nervous system.
在缺乏催化D-氨基酸氧化脱氨作用的D-氨基酸氧化酶的突变小鼠中，分析了福尔马林诱导的伤害性感受行为和N-甲基-D-天冬氨酸（NMDA）亚型谷氨酸受体介导的兴奋性突触传递。福尔马林诱导的舔舐反应的第二阶段（已知其一部分由脊髓中的NMDA受体介导）在突变小鼠中显著增强。通过紧密密封全细胞方法从脊髓背角神经元记录的NMDA受体介导的兴奋性突触后电流在突变小鼠中显著增强。本研究结果提供了另一系列证据，表明D-丝氨酸作为NMDA受体甘氨酸位点的内源性协同激动剂发挥作用，并增加了D-氨基酸氧化酶通过控制中枢神经系统中D-丝氨酸浓度发挥神经调节功能的可能性。
