Corticotropin-releasing hormone (CRH) depresses N-methyl-D-aspartate receptor-mediated current in cultured rat hippocampal neurons via CRH receptor type 1

被引:38
作者
Sheng, Hui [1 ]
Zhang, Yanmin [1 ]
Sun, Jihu [1 ]
Gao, Lu [1 ]
Ma, Bei [1 ]
Lu, Jianqiang [2 ,3 ]
Ni, Xin [1 ]
机构
[1] Second Mil Med Univ, Dept Physiol, Minist Educ, Key Lab Mol Neurobiol, Shanghai 200433, Peoples R China
[2] Second Mil Med Univ, Changhai Hosp, Minist Educ, Key Lab Mol Neurobiol, Shanghai 200433, Peoples R China
[3] Shanghai Univ Sport, Sch Kinesiol, Shanghai 200438, Peoples R China
关键词
D O I
10.1210/en.2007-1378
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
CRH, the primary regulator of the neuroendocrine responses to stress, has been shown to modulate synaptic efficacy and the process of learning and memory in hippocampus. However, effects of CRH on N-methyl-D-aspartate (NMDA) receptor, the key receptor for synaptic plasticity, remain unclear. In primary cultured hippocampal neurons, using the technique of whole-cell patch-clamp recordings, we found that CRH (1 pmol/liter to 10 nmol/liter) inhibited NMDA-induced currents in a dose-dependent manner. This effect was reversed by the CRH receptor type 1 (CRHR1) antagonist antalarmin but not by the CRHR2 antagonist astressin-2B, suggesting that CRHRl mediated the inhibitory effect of CRH. Investigations on the signaling pathways of CRH showed that CRH dose-dependently induced phosphorylated phospho-lipase C (PLC)-beta 3 expression and increased intracellular cAMP content in these cells. Blocking PLC activity with U73122 prevented CRH-induced depression of NMDA current, whereas blocking protein kinase A (1189) and adenylate cyclase (SQ22536) failed to affect the CRH-induced depression of NMDA current. Application of inositol-1,4,5-triphosphate receptor (IP3R) antagonist, Ca2+ chelators or protein kinase C (PKC) inhibitors also mainly blocked CRH-induced depression of NMDA currents, suggesting involvement of PLC/IP3R/ Ca2+ and PLC/PKC signaling pathways in CRH down-regulation of NMDA receptors. Our results suggest that CRH may exert neuromodulatory actions on hippocampus through regulating NMDA receptor function.
引用
收藏
页码:1389 / 1398
页数:10
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