神经保护多奈哌齐对谷氨酸会涉及刺激alpha7烟碱受体和门冬氨酸受体的内化。

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沈H, Kihara给T, Hongo村H,吴X,克姆WR, Shimohama年代,Akaike, Niidome T,杉本H

神经保护多奈哌齐对谷氨酸会涉及刺激alpha7烟碱受体和门冬氨酸受体的内化。

Br J杂志。2010年9月,161 (1):127 - 39。doi: 10.1111 / j.1476-5381.2010.00894.x。

PubMed ID
20718745 (在PubMed
]
文摘

背景和目的:谷氨酸会可能参与中枢神经系统缺血性损伤和神经退行性疾病,如阿尔茨海默氏症。多奈哌齐,乙酰胆碱酯酶抑制剂(疼痛),发挥神经保护作用。这里我们展示多奈哌齐的小说引起的神经保护机制。实验方法:细胞损伤在初级鼠神经元文化是由乳酸脱氢酶释放量化的。形态变化与神经保护作用的尼古丁和疼痛相关抑制剂被免疫染色评估。细胞表面水平的谷氨酸受体亚基,NR1和NR2A,使用生物素酰化进行了分析。免疫印迹是用来测量蛋白质含量的裂解caspase-3,总NR1、总NR2A和磷酸化NR1。免疫沉淀反应是用来测量协会NR1和突触后的蛋白质,psd - 95。细胞内钙(2 +)浓度测定fura 2-acetoxymethylester。半胱天冬酶存在活动使用酶底物,测定7-amino-4-methylcoumarin -DEVD (AMC)。 KEY RESULTS: Levels of NR1, a core subunit of the NMDA receptor, on the cell surface were significantly reduced by donepezil. In addition, glutamate-mediated Ca(2+) entry was significantly attenuated by donepezil. Methyllycaconitine, an inhibitor of alpha7 nicotinic acetylcholine receptors (nAChR), inhibited the donepezil-induced attenuation of glutamate-mediated Ca(2+) entry. LY294002, a phosphatidyl inositol 3-kinase (PI3K) inhibitor, had no effect on attenuation of glutamate-mediated Ca(2+) entry induced by donepezil. CONCLUSIONS AND IMPLICATIONS: Decreased glutamate toxicity through down-regulation of NMDA receptors, following stimulation of alpha7 nAChRs, could be another mechanism underlying neuroprotection by donepezil, in addition to up-regulating the PI3K-Akt cascade or defensive system.

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药物
药物靶点
药物 目标 类 生物 药理作用 行动
多奈哌齐 门冬氨酸受体(蛋白质组) 蛋白质组 人类
未知的
Downregulator
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