Grima G, Cuénod M, Pfeiffer S, Mayer B, Do K Q
Brain Research Institute, University of Zurich, Switzerland.
J Neurochem. 1998 Nov;71(5):2139-44. doi: 10.1046/j.1471-4159.1998.71052139.x.
The neuronal nitric oxide (NO) synthase generates NO from arginine. NO mediates its physiological effects mainly by stimulating the synthesis of cyclic GMP. We have investigated the role of the arginine availability on the NMDA-induced cyclic GMP accumulation in immature rat brain slices. The effect of NMDA was blocked by the inhibitor of the NO synthase, N(G)-nitro-L-arginine, and by the antagonist of ionotropic non-NMDA receptors, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). This inhibition was not due to a direct interaction of CNQX with the NMDA receptor, and it was overcome by the presence of exogenously applied arginine. CNQX also blocked the NMDA-evoked release of [3H]arginine from cerebellar slices. Moreover, the arginine uptake inhibitor L-lysine reduced the cyclic GMP response to NMDA significantly. Therefore, the extracellular arginine availability, which is dependent on the activation of ionotropic non-NMDA receptors, determines the rate of the NO biosynthesis by the neuronal NO synthase. Together with the reported release of arginine from glial cells upon activation of glial ionotropic non-NMDA receptors and the predominant glial localization of arginine, these data provide the first evidence of an essential role of the arginine transfer from glial cells to neurons for the biosynthesis of NO.
神经元型一氧化氮（NO）合酶可将精氨酸转化为NO。NO主要通过刺激环磷酸鸟苷（cGMP）的合成来介导其生理效应。我们研究了精氨酸的可利用性对未成熟大鼠脑片NMDA诱导的cGMP积累的作用。NMDA的作用被NO合酶抑制剂N(G)-硝基-L-精氨酸以及离子型非NMDA受体拮抗剂6-氰基-7-硝基喹喔啉-2,3-二酮（CNQX）所阻断。这种抑制并非由于CNQX与NMDA受体的直接相互作用，并且外源性添加精氨酸可克服这种抑制作用。CNQX还可阻断NMDA诱发的小脑切片中[3H]精氨酸的释放。此外，精氨酸摄取抑制剂L-赖氨酸可显著降低对NMDA的cGMP反应。因此，依赖于离子型非NMDA受体激活的细胞外精氨酸可利用性，决定了神经元型NO合酶的NO生物合成速率。结合已报道的胶质细胞离子型非NMDA受体激活后胶质细胞释放精氨酸以及精氨酸主要定位于胶质细胞的情况，这些数据首次证明了精氨酸从胶质细胞向神经元转移对于NO生物合成的重要作用。
