The effect of mGlu5 receptor positive allosteric modulators on signaling molecules in brain slices

被引:26
作者
Liu, F
Zhang, GM
Hornby, G
Vasylyev, D
Bowlby, M
Park, K
Gilbert, A
Marquis, K
Andree, TH
机构
[1] Wyeth Neurosci Discover Res, Princeton, NJ 08543 USA
[2] Wyeth Res, Exploratory Med Chem Chem & Screening Sci, Pearl River, NY 10965 USA
关键词
metabotropic glutamate receptor subtype 5; extracellular signal-regulated protein kinase; cyclic-AMP responsive element-binding protein; N-methyl D-aspartate receptor; N-{4-chloro-2-[(1,3-dioxo-1,3-dihydro-H-2-isoindol-2yl)-methyl]phenyl)-2-hydrobenzamide;
D O I
10.1016/j.ejphar.2006.02.003
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Positive allosteric modulators of metabotropic glutamate receptor subtype 5 (mGlu5) have promising therapeutic potential. The effects of selective mGlu5 receptor positive allosteric modulators on signaling molecules in brain slices have not been previously reported. The current study demonstrated that the selective mGlu5 receptor positive allosteric modulator, N-{4-chloro-2-[(1,3-dioxo-1,3-dihydro-H-2-isoindol-2yl)-methyl]phenyl}-2-hydrobenzamide (CPPHA) potentiated the response to a subthreshold concentration of 3,5-dihydroxy-phenylglycine (DHPG) on extracellular signal-regulated protein kinase (ERK) and cyclic-AMP responsive element-binding protein (CREB) activity, as well as N-methyl D-aspartate (NMDA) receptor subunit NR1 phosphorylation in cortical and hippocampal slices. These results suggest that allosteric modulators of mGlu5 receptor could have physiologically significant effects by potentiating the actions of glutamate. (c) 2006 Published by Elsevier B.V.
引用
收藏
页码:262 / 268
页数:7
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