Rawls S M, McGinty J F
Department of Anatomy and Cell Biology, East Carolina University School of Medicine, Greenville, North Carolina 27858-4354, USA.
J Neurochem. 1998 Feb;70(2):626-34. doi: 10.1046/j.1471-4159.1998.70020626.x.
The effects of local kappa receptor activation and blockade on extracellular striatal glutamate levels evoked by reverse microdialysis of L-trans-pyrrolidine-2,4-dicarboxylic acid (L-trans-PDC) were investigated. L-trans-PDC elevates extracellular glutamate levels in vivo by acting as a competitive substrate for plasma membrane excitatory amino acid transporters. The selective kappa-opioid receptor agonist U-69593 (1-100 nM) significantly attenuated L-trans-PDC-stimulated glutamate levels in a concentration-dependent manner. The selective kappa receptor antagonist nor-binaltorphimine (1-100 nM) reversed the U-69593-induced decrease in L-trans-PDC-evoked glutamate levels also in a concentration-dependent manner, indicating that the U-69593-induced reduction was mediated by kappa receptor activation. In addition, nor-binaltorphimine significantly elevated basal extracellular glutamate levels, implying that kappa receptors tonically regulate glutamate efflux in the striatum. Previous data from this laboratory have shown that L-trans-PDC-evoked extracellular glutamate levels are partially calcium-sensitive. The present study demonstrated that the inhibition of L-trans-PDC-evoked glutamate levels by reduced calcium perfusion was not altered by U-69593. Therefore, kappa receptors regulate the calcium-dependent component of L-trans-PDC-evoked extracellular glutamate levels in the striatum.
研究了局部κ受体激活和阻断对L-反式-吡咯烷-2,4-二羧酸（L-trans-PDC）反向微透析诱发的纹状体细胞外谷氨酸水平的影响。L-trans-PDC通过作为质膜兴奋性氨基酸转运体的竞争性底物来提高体内细胞外谷氨酸水平。选择性κ阿片受体激动剂U-69593（1-100 nM）以浓度依赖性方式显著减弱L-trans-PDC刺激的谷氨酸水平。选择性κ受体拮抗剂nor-binaltorphimine（1-100 nM）也以浓度依赖性方式逆转了U-69593诱导的L-trans-PDC诱发的谷氨酸水平降低，表明U-69593诱导的降低是由κ受体激活介导的。此外，nor-binaltorphimine显著提高了基础细胞外谷氨酸水平，这意味着κ受体对纹状体中的谷氨酸流出具有紧张性调节作用。该实验室以前的数据表明，L-trans-PDC诱发的细胞外谷氨酸水平部分对钙敏感。本研究表明，降低钙灌注对L-trans-PDC诱发的谷氨酸水平的抑制作用不受U-69593的影响。因此，κ受体调节纹状体中L-trans-PDC诱发的细胞外谷氨酸水平的钙依赖性成分。
