Role of excitatory amino acid receptors in the regulation of neurotransmitter release in the brain

本实验采用在体脑微透析技术，研究了N-甲基-D-天冬氨酸（NMDA）对清醒自由活动大鼠海马和纹状体细胞外神经递质（氨基酸、多巴胺和乙酰胆碱）浓度的影响。，这引起牛磺酸水平显着增加，未能促进多巴胺和其他氨基酸的释放。2)局部应用（10分钟）的NMDA不依赖性地增加天冬氨酸，谷氨酸，牛磺酸和多巴胺水平。低剂量（0.03 mM）的NMDA显著增加牛磺酸，而天冬氨酸、谷氨酸和多巴胺的显著增加仅在施加相对高剂量（>1 mM）的NMDA时观察到。3)通过微透析探针连续输注NMDA（1 mM）引起多巴胺和氨基酸（牛磺酸、谷氨酸等）的显著和显著增加。.特别是在多巴胺的情况下， 关于我们 4）在NMDA拮抗剂AP-5（1 mM）存在下，NMDA对牛磺酸和多巴胺的作用均被强烈抑制。NMDA对多巴胺的作用也被DNQX（非NMDA拮抗剂; 0.1-0.3 mM）抑制，而NMDA对牛磺酸的作用不受处理的影响。持续输注α-氨基-3-羟基-5-甲基-异恶唑-4-丙酸（AMPA ; 1 mM），一种非NMDA激动剂，也增加了牛磺酸和多巴胺。AMPA的作用可被DNQX抑制，而AP-5不抑制。5)NMDA和AMPA对多巴胺的增加作用在高渗溶液（+150 mM蔗糖）的输注下减弱，而NMDA和AMPA对牛磺酸的作用不受治疗的影响。6)结果表明，NMDA受体在细胞外神经递质浓度的调节中起重要作用，牛磺酸对小剂量NMDA的局部应用比谷氨酸、多巴胺等更敏感。这些结果还表明，高浓度的NMDA，这导致增加内源性谷氨酸的释放，通过NMDA和非NMDA受体作用于多巴胺，并且NMDA的作用可能与细胞肿胀有关。少

In vivo brain microdialysis was applied to study the effect of N-methyl-D-aspartate (NMDA) on the extracellular concentrations of neurotransmitters (amino acide, dopamine and acetylcholine) in the hippocampus and striatum of awake freely moving rats.1) Systemic administration of NMDA (10-30 mg/kg, i.p.) , which induced a significant increase of taurine level, failed to facilitate the release of dopamine and other amino acids. 2) The local application (for 10 min) of NMDA does-dependently increased aspartate, glutamate, taurine and dopamine levels. Taurine was increased significantly by a low does (0.03 mM) of NMDA,while significant increases in aspartate, glutamate and dopamine were only observed when relatively high doses (>1 mM) of NMDA were applied. 3) The continuous infusion of NMDA (1 mM) via the microdialysis probe caused significant and marked increases of dopamine and amino acids (taurine, glutamate etc.) . Especially in the case of dopamine, desensitization was observed after … More 1 hr of continuous application of NMDA.4) In the preaence of AP-5 (a NMDA antagonist ; 1 mM) , the effect of NMDA on both the taurine and dopamine was strongly inhibited. The effect of NMDA on dopamine was also inhibited by DNQX (a non-NMDA antagonist ; 0.1-0.3 mM) while the effect of NMDA on taurine was not affected by the treatment. The continuous infusion of alpha-amino-3-hudroxy-5-methyl-isoxazole-4-propionic acid (AMPA ; 1mM) , a non-NMDA agonist, also increased taurine and dopamine. The effect of AMPA was inhibited by the treatment of DNQX but not by the treatment of AP-5) . 5) The increasing effects of NMDA and AMPA on dopamine were diminished under the infusion of a hypertonic solution (+150 mM sucrose) while the effects of NMDA and AMPA on taurine were not affected by the treatment. 6) The continuous infusion of NMDA (1 mM) caused significant increase of acetylcholine level.7) These results suggest that NMDA receptor plays an important role in the regulation of extracellular neurotransmitter concentrations and that taurine is apparently sensitive to the local application of low dose NMDA than glutamate, dopamine etc.. These results also suggest that high concentrations of NMDA,which lead to increase a release of endogenous glutamate, act on dopamine via both NMDA and non-NMDA receptors and that the effect of NMDA might be related to cell swelling. Less