Rawls S M, Mcginty J F
Department of Anatomy and Cell Biology, East Carolina University School of Medicine, Greenville, North Carolina, USA.
J Pharmacol Exp Ther. 1998 Jul;286(1):91-8.
Regulation of extracellular glutamate levels by muscarinic receptors in the striatum of unanesthetized rats was investigated by microdialysis. Extracellular glutamate levels were elevated by intrastriatal perfusion of L-trans-pyrrolidine-2,4-dicarboxylic acid (L-trans-PDC), a competitive substrate of plasma membrane excitatory amino acid transporters. The nonselective muscarinic agonist, oxotremorine (0.5-54 microM) significantly decreased L-trans-PDC-evoked glutamate levels in a concentration-dependent manner. Scopolamine (0.1-10 microM), a nonselective muscarinic receptor antagonist, reversed the effect of oxotremorine, which confirms that muscarinic receptor activation mediated the reduction of L-trans-PDC-evoked glutamate levels. In addition, scopolamine (10 microM) significantly elevated basal extracellular glutamate levels, an effect prevented by oxotremorine, which suggests that acetylcholine tonically regulates glutamatergic transmission in the striatum. Previous data from this laboratory have shown that L-trans-PDC-evoked glutamate levels are partially calcium-dependent. The present study demonstrated that attenuation of L-trans-PDC-evoked glutamate levels by reduced calcium was not altered by oxotremorine. Therefore, it is likely that muscarinic receptors regulate calcium-dependent glutamate release evoked by L-trans-PDC.
通过微透析研究了未麻醉大鼠纹状体中毒蕈碱受体对细胞外谷氨酸水平的调节作用。通过纹状体内灌注L-反式-吡咯烷-2,4-二羧酸（L-反式-PDC，质膜兴奋性氨基酸转运体的竞争性底物）可升高细胞外谷氨酸水平。非选择性毒蕈碱激动剂氧化震颤素（0.5 - 54 microM）以浓度依赖性方式显著降低L-反式-PDC诱发的谷氨酸水平。非选择性毒蕈碱受体拮抗剂东莨菪碱（0.1 - 10 microM）可逆转氧化震颤素的作用，这证实毒蕈碱受体激活介导了L-反式-PDC诱发的谷氨酸水平降低。此外，东莨菪碱（10 microM）显著升高基础细胞外谷氨酸水平，而氧化震颤素可阻止该效应，这表明乙酰胆碱对纹状体中的谷氨酸能传递起紧张性调节作用。该实验室先前的数据表明，L-反式-PDC诱发的谷氨酸水平部分依赖于钙。本研究表明，氧化震颤素不会改变因钙减少而导致的L-反式-PDC诱发的谷氨酸水平降低。因此，毒蕈碱受体很可能调节L-反式-PDC诱发的钙依赖性谷氨酸释放。
