Journal of Pharmacological Sciences
Online ISSN : 1347-8648
Print ISSN : 1347-8613
ISSN-L : 1347-8613
Full Papers
Mechanisms of Chronic Nicotine Treatment–Induced Enhancement of the Sensitivity of Cortical Neurons to the Neuroprotective Effect of Donepezil in Cortical Neurons
Yuki Takada-TakatoriToshiaki KumeYasuhiko IzumiTetsuhiro NiidomeTakeshi FujiiHachiro SugimotoAkinori Akaike
Author information
JOURNAL FREE ACCESS

2010 Volume 112 Issue 3 Pages 265-272

Details
Abstract

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.

Information related to the author
© The Japanese Pharmacological Society 2010
Previous article Next article
feedback
Top