Antagonism of the mGlu5 agonist 2-chloro-5-hydroxyphenylglycine by the novel selective mGlu5 antagonist 6-methyl-2(phenylethynyl)-pyridine (MPEP) in the thalamus
Antagonism of the mGlu5 agonist 2-chloro-5-hydroxyphenylglycine by the novel selective mGlu5 antagonist 6-methyl-2(phenylethynyl)-pyridine (MPEP) in the thalamus
复制标题
DOI：
10.1038/sj.bjp.0702677
复制
发表时间：
1999-07-01
影响因子：
7.3
通讯作者：
Kuhn, R
中科院分区：
文献类型：
--
作者：
Salt, TE;Binns, KE;Kuhn, R
我们之前的工作表明，I 组 mGlu 受体参与体内丘脑的感觉处理。然而，由于缺乏特异性配体，尚不可能明确证明 mGlu5 的参与。因此，我们对激动剂 (R,S)-2-氯-5-羟基苯基甘氨酸 [CHPG] 和新型 mGlu5 拮抗剂 6-甲基-2-(苯乙炔基)-吡啶 [MPEP] 的体内作用进行了初步研究，以表征它们对功能研究的适用性。与广谱 mGlu 激动剂 (1S,3R)-1-氨基环戊烷-1,3-二羧酸酯相比，离子导入 MPEP 选择性拮抗单只大鼠丘脑神经元对 CHPG 的兴奋反应。相比之下，已建立的 mGlu1 和 mGlu5 拮抗剂 (S)-4-羧基苯基甘氨酸降低了对两种激动剂的反应。这些发现首次证明了 CHPG 的体内作用及其选择性 mGlu5 拮抗剂的拮抗作用。此外，MPEP 似乎是 mGlu5 功能研究的良好工具。
Our previous work has shown that Group I mGlu receptors participate in thalamic sensory processing in viva. However, unequivocal demonstration of mGlu5 participation has not been possible due to the lack of specific ligands. We have therefore made a preliminary study of the in vivo actions of the agonist (R,S)-2-Chloro-5-hydroxyphenylglycine [CHPG] and the novel mGlu5 antagonist 6-methyl-2-(phenylethynyl)-pyridine [MPEP] in order to characterize their suitability for functional studies. Iontophoretically administered MPEP selectively antagonized excitatory responses of single rat thalamic neurones to CHPG compared to the broad-spectrum mGlu agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate. In contrast, the established mGlu1 and mGlu5 antagonist (S)-4-carboxyphenylglycine reduced responses to both agonists. These findings are the first demonstration of an in vivo action of CHPG and its antagonism by a selective mGlu5 antagonist. Furthermore MPEP appears to be a good tool for functional studies of mGlu5.