Mechanisms of Chronic Nicotine Treatment–Induced Enhancement of the Sensitivity of Cortical Neurons to the Neuroprotective Effect of Donepezil in Cortical Neurons

Journal of Pharmacological Sciences

Akinori Akaike³  Hachiro Sugimoto¹  Tetsuhiro Niidome¹  Toshiaki Kume³  Takeshi Fujii²  Yasuhiko Izumi³  Yuki Takada-Takatori² 

[1] Department of Neuroscience for Drug Discovery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan;Department of Pharmacology, Faculty of Pharmaceutical Sciences, Doshisha Women’s College, Japan;Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan

关键词: neuroprotection;    Alzheimer’s disease;    nicotine;    nicotinic acetylcholine receptor up-regulation;    phosphatidylinositol 3-kinase;   

DOI  :  10.1254/jphs.09311FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(24)We have previously shown that chronic donepezil treatment induces nicotinic acetylcholine receptor up-regulation and enhances the sensitivity of the neurons to the neuroprotective effect of donepezil. Further analyses revealed that the nicotinic receptor is involved in this enhancement. In this study, we examined whether nicotinic receptor stimulation is sufficient to make neurons more sensitive to donepezil. We treated primary cultures of rat cortical neurons with nicotine and confirmed that chronic nicotine treatment induced nicotinic receptor up-regulation and made the neurons more sensitive to the neuroprotective effects of donepezil. Analyses with receptor antagonists and kinase inhibitors revealed that the effects of chronic nicotine treatment are mediated by nicotinic receptors and their downstream effectors including phosphatidylinositol 3-kinase. In contrast to chronic donepezil treatment that enhanced the level of nicotine-induced Ca2+ influx, chronic nicotine treatment did not significantly alter the level of Ca2+ influx.

【 授权许可】

Unknown