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

在体脑微透析法研究了N-甲基-D-天冬氨酸(NMDA)对清醒自由活动大鼠海马区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。1)全身注射NMDA(10~30 mg/kg，ip)，牛磺酸水平显著升高，但不能促进多巴胺和其他氨基酸的释放。2)局部应用NMDA(10min)可依赖地增加天冬氨酸、谷氨酸、牛磺酸和多巴胺的水平。低剂量(0.03 mM)NMDA可显著增加牛磺酸的含量，而天冬氨酸、谷氨酸和多巴胺只有在较高剂量(-gt；1 mM)时才能显著增加。3)微透析探头持续注入NMDA(1 MM)可显著增加多巴胺和氨基酸(牛磺酸、谷氨酸等)的含量。特别是在多巴胺的情况下，…后观察到脱敏4)在NMDA拮抗剂AP-5(1 MM)作用下，NMDA对牛磺酸和多巴胺的作用均被强烈抑制。非NMDA拮抗剂DNQX(0.1-0.3 mM)也可抑制NMDA对多巴胺的作用，但对牛磺酸的作用不受影响。持续输注非alpha-amino-3-hudroxy-5-methyl-isoxazole-4-propionic激动剂AMPA酸(1 MM)也增加牛磺酸和多巴胺。AMPA的作用可被DNQX抑制，但不被AP-5所抑制)。5)高渗液(150 mM蔗糖)可减弱NMDA和AMPA对多巴胺的增加作用，而对牛磺酸的作用不受影响。7)提示NMDA受体在细胞外神经递质浓度的调节中起重要作用，牛磺酸对局部应用小剂量NMDA的敏感性明显高于谷氨酸、多巴胺等。这些结果还表明，高浓度的NMDA导致内源性谷氨酸的释放增加，通过NMDA和非NMDA受体作用于多巴胺，NMDA的作用可能与细胞肿胀有关。较少

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