It has been well accepted that d-serine may be an exclusive endogenous coagonist for the N-methyl-d-aspartate (NMDA)-type glutamate receptor in mammalian forebrain regions. We have recently found by using an in vivo dialysis method that an intra-medial prefrontal cortex infusion of S-α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (S-AMPA), a selective AMPA-type glutamate receptor agonist, causes a reduction in the extracellular levels of d-serine in a calcium-permeable AMPA receptor antagonist-sensitive manner. The inhibitory influence by the AMPA receptor on the extracellular d-serine, however, contradicts the data obtained from in vitro experiments that the AMPA receptor stimulation leads to facilitation of the d-serine liberation. This discrepancy appears to be due to the different cell setups between the in vivo and in vitro preparations. From the viewpoints of the previous reports indicating (1) the neuronal presence of d-serine synthesizing enzyme, serine racemase, and d-serine-like immunoreactivity and (2) the same high tissue concentrations of d-serine in the glia-enriched white matter and in the neuron-enriched gray matter of the mammalian neocortex, we have now investigated in the mouse medial prefrontal cortex, the effects of attenuation of neuronal and glial activities, by tetrodotoxin or fluorocitrate, respectively, on the S-AMPA-induced downregulation of the extracellular d-serine contents. In vivo dialysis studies revealed that a local infusion of tetrodotoxin or fluorocitrate eliminated the ability of S-AMPA given intra-cortically to cause a significant decrease in the dialysate concentrations of d-serine without affecting the elevating effects of S-AMPA on those of glycine, another intrinsic coagonist for the NMDA receptor. These findings suggest that the control by the AMPA receptor of the extracellular d-serine levels could be modulated by the neuronal and glial activities in the prefrontal cortex. It cannot be excluded that fluorocitrate would indirectly alter the modulation by changing synaptic neurotransmission via glial activity attenuation as previously reported.

它已被广泛接受的是d -丝氨酸可以是用于异源性coagonist Ñ甲基d在哺乳动物前脑区域天冬氨酸（NMDA）型谷氨酸受体。我们最近发现，通过体内透析方法，可以将选择性AMPA型S-α-氨基-3-羟基-1-甲基5-甲基-4-异恶唑-丙酸酯（S-AMPA）进行内侧前额叶皮层内输注。谷氨酸受体激动剂以钙可渗透的AMPA受体拮抗剂敏感的方式引起d-丝氨酸的细胞外水平降低。但是，AMPA受体对细胞外d-丝氨酸的抑制作用与从体外获得的数据相矛盾。关于AMPA受体刺激导致d-丝氨酸释放促进的实验。这种差异似乎是由于体内和体外制剂之间的细胞设置不同所致。从以前的报告的观点表明（1）d-丝氨酸合成酶，丝氨酸消旋酶和d-丝氨酸样免疫反应的神经元存在和（2）相同的高组织浓度d哺乳动物新皮层中神经胶质细胞丰富的白质和神经元丰富的灰色质中的丝氨酸，我们现在已经在小鼠内侧前额叶皮层中研究了河豚毒素或氟柠檬酸盐分别对神经元和神经胶质活动的影响。对S-AMPA诱导的细胞外d-丝氨酸含量的下调。体内透析研究表明，河豚毒素或氟柠檬酸的局部输注消除了皮质内给予S-AMPA导致d透析液浓度显着降低的能力。-丝氨酸而不影响S-AMPA对甘氨酸的增效作用，甘氨酸是NMDA受体的另一种内在激动剂。这些发现表明，AMPA受体对细胞外d-丝氨酸水平的控制可能受额叶皮层神经元和神经胶质活动的调节。不能排除的是，氟柠檬酸会通过胶质细胞活性减弱来改变突触神经传递，从而间接改变调节作用，如先前报道的那样。