| 朱含 颜颖慧 赵兰雪 葛艳慧 邱瑜.M1乙酰胆碱受体对AMPA受体GluA1-Ser831 位点的调控作用[J].,2016,16(21):4001-4005 |
| M1乙酰胆碱受体对AMPA受体GluA1-Ser831 位点的调控作用 |
| Modulation for the GluA1-Ser831 Site of AMPA Receptor byM1 MuscarinicAcetylcholine Receptor |
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| DOI： |
| 中文关键词: M1 乙酰胆碱受体 AMPA 受体 GluA1-Ser831 位点 磷酸化 |
| 英文关键词: M1 muscarinic acetylcholine receptor AMPA receptor GluA1-Ser831 Site Phosphorylation |
| 基金项目:国家自然科学基金面上项目（81473217） |
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| 中文摘要: |
| 目的：从海马神经元谷氨酸离子型受体--AMPA受体亚基GluA1 的831 位丝氨酸（GluA1 Ser831）磷酸化角度，探讨M1 乙
酰胆碱受体对AMPA 受体GluA1 亚基的调控作用及作用机制。方法：本研究以成熟的原代海马神经元为实验对象，用不易被降
解的卡巴胆碱（Carbachol，CCh）作为胆碱受体激动剂，以免疫印迹法作为蛋白和磷酸化蛋白的主要检测手段，结合不同蛋白抑制
剂研究M1受体调控AMPA 受体GluA1 亚基的关键信号分子及其机制。结果：①与对照组相比，CCh 组Ser831 的磷酸化水平显
著升高。②CCh 促进Ser831 磷酸化的现象在M1 受体选择性拮抗剂哌仑西平（Pirenzepine）+CCh 组消失，CCh升高GluA1-Ser831
磷酸化水平的作用由M1 受体介导。③蛋白激酶C (Protein kinase C，PKC)抑制剂白屈菜红碱（Chelerythrine chloride，CHCL）能对
抗CCh 促进GluA1-Ser831 位点磷酸化的作用，而钙/ 钙调素依赖性蛋白激酶II (Calcium/calmodulin-dependent kinase II，CaMKII)
抑制剂KN62 不能对抗CCh 的作用。④为检测体内GluA1-Ser831 的磷酸化情况，用小鼠海马组织定位注射CCh 和CHCL，CCh
组小鼠海马组织GluA1-Ser831 位点的磷酸化水平升高，CHCL 能对抗这种作用，PKC 介导了M1 受体激活所导致的Glu-
A1-Ser831 磷酸化水平的升高。结论：M1 受体通过激活PKC 促进GluA1-Ser831 的磷酸化。 |
| 英文摘要: |
| Objective:By monitoring the phosphorylation of GluA1-Ser831 in hippocampal neurons, we explored the underlying
mechanism of modulation of AMPA receptor by M1 muscarinic acetylcholine receptor.Methods:This study made use of the maturely
cultured primary hippocampal neurons and carbachol (CCh), an acetylcholine receptor agonist which was resistant to degradation. Western
Blot was used as the main method for the detection of protein and protein phosphorylation, and a variety of different protein inhibitors
were utilized to study the signaling molecules of M1 receptor regulating phosphorylation of GluA1 subunit.Results:①CCh increased the
phosphorylation of GluA1 at Ser831 compared with control group. ②The up-regulated phosphorylation of GluA1-Ser831 by CCh was attenuated
by added Pirenzepine in CCh, suggesting that CCh acted through M1 receptor to increase phosphorylation of GluA1-Ser831. ③
PKC inhibitor CHCL totally blocked the phosphorylation of Ser831 induced by CCh, whereas CAMKII inhibitor KN62 did not block the
effects of CCh. ④ The hippocampus of mice were injected with CCh or CHCL to examine the effects in vivo. CCh increased the phosphorylation
of GluA1 at Ser831. CHCL totally attenuated the increase of GluA1-Ser831 phosphorylation induced by CCh.Conclusion:The phosphorylation of GluA1 at Ser831 was promoted by M1 receptor through PKC. |
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