Up-regulation of nicotinic acetylcholine receptors by central-type acetylcholinesterase inhibitors in rat cortical neurons

Toshiaki Kume, Mitsuhiro Sugimoto, Yuki Takada, Toshiaki Yamaguchi, Atsushi Yonezawa, Hiroshi Katsuki, Hachiro Sugimoto, Akinori Akaike

研究成果: Article査読

59 被引用数 (Scopus)

抄録

We previously reported that donepezil, a central-type acetylcholinesterase inhibitor, showed neuroprotective action via α4-and α7-nicotinic acetylcholine receptors against glutamate neurotoxicity in rat cortical culture. The present study was performed to investigate whether the neuroprotective action of acetylcholinesterase inhibitors is accompanied by the alteration of expression and function of nicotinic receptors. Four days treatment with acetylcholinesterase inhibitors (10 μM) enhanced the nicotine-induced increase of the intracellular calcium concentration. Immunoblot analysis revealed that donepezil increased both α4 and α7 subunit proteins. Donepezil and galanthamine increased the number of cells expressing α4- and α7-nicotinic receptors in immunocytochemical analysis. We examined whether up-regulation of nicotinic receptors affected the neuroprotective action of acetylcholinesterase inhibitors. Under up-regulating conditions, donepezil and galanthamine exerted neuroprotective action at lower concentrations. These results suggest that donepezil and galanthamine up-regulate nicotinic receptors in cortical neurons, and that the up-regulation of nicotinic receptors may make cortical neurons more sensitive to the neuroprotective action of donepezil and galanthamine.

本文言語English
ページ(範囲)77-85
ページ数9
ジャーナルEuropean journal of pharmacology
527
1-3
DOI
出版ステータスPublished - 2005 12月 19
外部発表はい

ASJC Scopus subject areas

  • 薬理学

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