Lada M W, Vickroy T W, Kennedy R T
Department of Chemistry, University of Florida, Gainesville 32611, USA.
J Neurochem. 1998 Feb;70(2):617-25. doi: 10.1046/j.1471-4159.1998.70020617.x.
Extracellular levels of glutamate (Glu) and aspartate (Asp) were measured at 5-s intervals in the striatum of chloral hydrate-anesthetized rats by using microdialysis coupled to an automated assay system based on capillary electrophoresis with laser-induced fluorescence. Application of a single 10-s train of depolarizing pulses to the prefrontal cortex caused a rapid increase in Glu and Asp concentrations (200-300% of basal value), which returned to basal level within 60 s. The stimulated rise in Glu and Asp concentrations was blocked completely by 2 microM tetrodotoxin or depletion of extracellular Ca2+, suggesting a neuronal origin of the Glu and Asp. Infusion of the Glu transport inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid (200 microM) increased resting Glu and Asp levels by 300-500% without altering electrically stimulated changes in Glu and Asp concentration. Stimulated Glu and Asp concentration changes were suppressed by 91 and 73%, respectively, by the metabotropic Glu receptor agonist (1S,3R)-1-aminocyclopentane-trans-1,3-dicarboxylate (200 microM). This effect was blocked by the metabotropic Glu receptor antagonist (RS)-alpha-methylcarboxyphenylglycine (MCPG; 200 microM). MCPG alone produced no effect on electrically stimulated changes in Glu and Asp levels; however, in the presence of L-trans-pyrrolidine-2,4-dicarboxylic acid, MCPG produced a five- to sixfold increase in stimulated overflow. Based on these results, it is concluded that release of Glu and Asp from corticostriatal neurons can be inhibited by activation of metabotropic Glu autoreceptors, which may be an important determinant of excitatory transmission at striatal synapses.
通过使用与基于毛细管电泳和激光诱导荧光的自动检测系统联用的微透析技术，以5秒的间隔测量水合氯醛麻醉大鼠纹状体中谷氨酸（Glu）和天冬氨酸（Asp）的细胞外水平。对前额叶皮层施加单次持续10秒的去极化脉冲串，会导致Glu和Asp浓度迅速升高（达到基础值的200 - 300%），并在60秒内恢复到基础水平。Glu和Asp浓度的刺激升高被2微摩尔的河豚毒素或细胞外Ca2+耗尽完全阻断，表明Glu和Asp来源于神经元。注入Glu转运抑制剂L-反式-吡咯烷-2,4-二羧酸（200微摩尔）可使静息状态下的Glu和Asp水平升高300 - 500%，而不改变电刺激引起的Glu和Asp浓度变化。代谢型Glu受体激动剂（1S,3R）-1-氨基环戊烷-反式-1,3-二羧酸（200微摩尔）分别使刺激引起的Glu和Asp浓度变化抑制了91%和73%。这种作用被代谢型Glu受体拮抗剂（RS）-α-甲基羧基苯基甘氨酸（MCPG；200微摩尔）阻断。单独使用MCPG对电刺激引起的Glu和Asp水平变化没有影响；然而，在存在L-反式-吡咯烷-2,4-二羧酸的情况下，MCPG使刺激后的溢出增加了五到六倍。基于这些结果，可以得出结论，代谢型Glu自身受体的激活可抑制皮质纹状体神经元释放Glu和Asp，这可能是纹状体突触兴奋性传递的一个重要决定因素。
