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Effect of chronic nicotine treatment on localization of neuronal nicotinic acetylcholine receptors at cellular level
Author(s) -
Pakkanen Jukka S.,
Stenfors Jan,
Jokitalo Eija,
Tuominen Raimo K.
Publication year - 2006
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20249
Subject(s) - nicotine , acetylcholine receptor , nicotinic agonist , chemistry , pharmacology , in vivo , in vitro , microbiology and biotechnology , endoplasmic reticulum , nicotinic acetylcholine receptor , receptor , biology , biochemistry , neuroscience
Chronic nicotine treatment increases the number of neuronal nicotinic acetylcholine receptors (nAChRs). Localization of nAChRs at a cellular level determines their functional role. However, changes in the localization of nAChRs caused by chronic nicotine treatment are not well known. In this study, we have examined the effects of chronic nicotine treatment on α7 and β2 nAChR subunits in vitro in cell lines and in vivo in mouse striatum. In vitro, two different cell lines were used, SH‐SY5Y cells endogenously expressing several nAChR subtypes and SH‐EP1‐hα7 cells, transfected with the human α7 nAChR subunit gene. Effects of chronic nicotine treatment (10 μM, 3 days) were studied in vitro by using confocal and electron microscopy and calcium fluorometry. In vitro in SH‐SY5Y cells, α7 and β2 subunits formed groups, unlike α7 subunits in SH‐EP1‐hα7 cells, which were partially localized on endoplastic reticulum. Chronic nicotine treatment did not change the localization of nAChRs in endosomes, but caused clustering of α7 subunits in SH‐EP1‐hα7 cells. In vivo, nicotine was given to mice in their drinking water for 7 weeks. Results showed that α7 and β2 subunits formed groups, and that chronic nicotine treatment increased the size of the clusters. As a conclusion, our data show that there are large intracellular pools of nAChR subunits, which are partially localized on endoplastic reticulum. Chronic nicotine treatment does not change endocytotic trafficking of nAChRs. Chronic nicotine treatment increased clustering of nAChRs, which could have a role in the release of dopamine (DA) evoked by nicotine. Synapse 59:383–393, 2006. © 2006 Wiley‐Liss, Inc.