| 摘要: |
| 目的:研究促肾上腺皮质激素释放激素（CRH）对原代培养海马神经元谷氨酸诱发电流（IGLU）的调节作用，并初步探讨其可能机制。方法:应用免疫荧光细胞化学方法观察原代培养的大鼠海马神经元CRH两型受体的表达；通过全细胞膜片钳技术研究CRH对海马神经元IGLU的调节作用及其可能涉及的胞内信号通路。结果:CRH作用2 min明显抑制海马神经元IGLU，且呈剂量依赖性；细胞外给予CRH受体广谱拮抗剂α-helical CRH或CRHR1特异性拮抗剂antalarmin能完全阻断CRH对IGLU的抑制作用，CRHR2特异性拮抗剂astressin-2B对此没有明显作用；细胞内给予蛋白激酶C（protein kinase C, PKC）的抑制剂G6976可阻断CRH对IGLU的抑制作用。结论:多肽类激素CRH可抑制原代培养的海马神经元IGLU，这种作用由CRHR1介导，并可能涉及PKC信号通路。 |
| 关键词: 促肾上腺皮质激素释放激素 谷氨酸 海马 电生理学 |
| DOI：10.3724/SP.J.1008.2009.0233 |
| 投稿时间：2008-07-08修订日期：2008-09-23 |
| 基金项目:教育部长江学者与创新团队计划(IRT0528). |
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| Regulatory effect of corticotrophin-releasing hormone on glutamate-mediated current in cultured hippocampal neurons |
| SHENG Hui1, MA Bei1, L Jian-qiang2, SUN Ting-ting1, NI Xin1* |
| (1.Department of Physiology, College of Basic Medical Sciences, Second Military Medical University, Shanghai 200433, China;2.School of Kinesiology, Shanghai University of Sport, Shanghai 200438) |
| Abstract: |
| Objective:To examine the regulatory effect of corticotrophin-releasing hormone (CRH) on glutamate-mediated current (IGLU) in cultured hippocampal neurons and to study the related mechanism. Methods: Immunofluorescence analysis was used to investigate whether the cultured hippocampal neurons express CRH receptors, and the whole-cell patch-clamp technique was used to examine the direct modulation of CRH on IGLU and the possible intracellular signal pathway. Results: Two minutes’ exposure to CRH obviously depressed IGLU in the neurons in a dose-dependent manner. CRH receptor antagonist α-helical CRH or CRH receptor type 1 (CRHR1) antagonist antalarmin completely blocked CRH-induced depression of IGLU; whereas, CRH receptor type 2 (CRHR2) antagonist astressin-2B failed to block the effects of CRH. Application of the PKC inhibitor G6976 totally blocked the CRH-induced decrease of IGLU. Conclusion: CRH can inhibit IGLU in primary cultured hippocampal neurons, which is mediated by CRHR1 and may involve the PKC signal pathway. |
| Key words: corticotropin-releasing hormone glutamate hippocampus electrophysiology |
