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Effects of chronic nicotine on heteromeric neuronal nicotinic receptors in rat primary cultured neurons
Author(s) -
Lomazzo Ermelinda,
Hussmann Gregory P.,
Wolfe Barry B.,
Yasuda Robert P.,
Perry David C.,
Kellar Kenneth J.
Publication year - 2011
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2011.07408.x
Subject(s) - nicotine , epibatidine , acetylcholine receptor , nicotinic agonist , receptor , protein subunit , nicotinic acetylcholine receptor , chemistry , pharmacology , endocrinology , biology , medicine , microbiology and biotechnology , neuroscience , biochemistry , gene
J. Neurochem. (2011) 119 , 153–164. Abstract Nicotine increases the number of neuronal nicotinic acetylcholine receptors (nAChRs) in brain. This study investigated the effects of chronic nicotine treatment on nAChRs expressed in primary cultured neurons. In particular, we studied the chronic effects of nicotine exposure on the total density, surface expression and turnover rate of heteromeric nAChRs. The receptor density was measured by [ 125 I]epibatidine ([ 125 I]EB) binding. Untreated and nicotine‐treated neurons were compared from several regions of embryonic (E19) rat brain. Twelve days of treatment with 10 μM nicotine produced a twofold up‐regulation of nAChRs. Biotinylation and whole‐cell binding studies indicated that up‐regulation resulted from an increase in the number of cell surface receptors as well as intracellular receptors. nAChR subunit composition in cortical and hippocampal neurons was assessed by immunoprecipitation with subunit‐selective antibodies. These neurons contain predominantly α4, β2 and α5 subunits, but α2, α3, α6 and β4 subunits were also detected. Chronic nicotine exposure yielded a twofold increase in the β2‐containing receptors and a smaller up‐regulation in the α4‐containing nAChRs. To explore the mechanisms of up‐regulation we investigated the effects of nicotine on the receptor turnover rate. We found that the turnover rate of surface receptors was > 2 weeks and chronic nicotine exposure had no effect on this rate.