Laboratory of Neurobiology and Experimental Neurology, Department of Physiology, Faculty of Medicine, University of La Laguna, La Laguna, Tenerife, Canary Islands, Spain.
Neuropharmacology. 2012 Dec;63(8):1308-14. doi: 10.1016/j.neuropharm.2012.08.007. Epub 2012 Aug 31.
Despite evidence suggesting the interaction among glutamate (GLU), dopamine (DA) and ascorbic acid (AA) in the striatum, their actions are often studied separately. Microdialysis was used here to quantify the extracellular interaction among GLU-DA-AA in the striatum of rats, an interaction which was compared with those studied in the substantia nigra (SN). Perfusion of GLU by reverse microdialysis increased DA and decreased 3,4-dihydroxyphenylacetic acid (DOPAC) in the extracellular medium of the striatum, but increased both DA and DOPAC in the SN. The increase of extracellular DA-concentration induced by the local DA-perfusion decreased the extracellular level of GLU and glutamine, an effect that, as suggested by the GLU and glutamine increase observed after the haloperidol administration, probably involves the D2 dopamine receptor. Local administration of AA increased the extracellular DA, decreased DOPAC and had no effect on GLU and glutamine. Present data suggest that, in the striatum, GLU-release inhibits DA-uptake, DA-release inhibits GLU-release, and AA-release prevents DA-oxidation increasing its extracellular diffusion. These effects were different in the SN where GLU probably promoted the DA-release instead of inhibiting the DA-uptake as presumably occurred in the striatum. Present data denote a marked GLU-DA-AA interaction in the striatum, which might be relevant for the pharmacological control of basal ganglia disorders.
尽管有证据表明谷氨酸(GLU)、多巴胺(DA)和抗坏血酸(AA)在纹状体中的相互作用,但它们的作用通常是分开研究的。这里使用微透析技术来量化大鼠纹状体中 GLU-DA-AA 之间的细胞外相互作用,并将其与在黑质(SN)中研究的相互作用进行比较。通过逆行微透析灌注 GLU 会增加纹状体细胞外介质中的 DA 并降低 3,4-二羟基苯乙酸(DOPAC),但会增加 SN 中的 DA 和 DOPAC。局部 DA 灌注引起的细胞外 DA 浓度增加会降低 GLU 和谷氨酰胺的细胞外水平,这种作用可能涉及 D2 多巴胺受体,如在给予氟哌啶醇后观察到的 GLU 和谷氨酰胺增加所表明的那样。局部给予 AA 会增加细胞外 DA,降低 DOPAC,对 GLU 和谷氨酰胺没有影响。目前的数据表明,在纹状体中,GLU 释放抑制 DA 摄取,DA 释放抑制 GLU 释放,AA 释放防止 DA 氧化,增加其细胞外扩散。这些作用在 SN 中不同,在 SN 中,GLU 可能促进 DA 释放而不是像在纹状体中那样抑制 DA 摄取。目前的数据表明纹状体中存在明显的 GLU-DA-AA 相互作用,这可能与基底神经节疾病的药理学控制有关。