Effects of chronic nicotine on heteromeric neuronal nicotinic receptors in rat primary cultured neurons
Open accessAbstract
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 [¹²⁵I]epibatidine ([¹²⁵I]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.
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Upregulation of α4β2 nAChRs may involve increased receptor protein through post-translational events, possibly including changes in nAChR maturation and trafficking.
“Thus, upregulation of α4β2 nAChRs may involve an increase in receptor protein through post-translational events that may include changes in nAChR maturation and trafficking (Darsow et al., 2005; Kane et al., 2004; Lomazzo et al., 2011; Rezvani et al., 2007).”
From The duration of nicotine withdrawal-associated deficits in contextual fear conditioning parallels changes in hippocampal high affinity nicotinic acetylcholine receptor upregulation (2012) · cites this paper as Lomazzo et al., 2011
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- Authors
- Lomazzo, E., Hussmann, G. P., Wolfe, B. B., Yasuda, R. P., Perry, D. C., & Kellar, K. J.
- Affiliations
- Georgetown University (US)
- George Washington University (US)
- Corresponding author
- Kellar, Kenneth J.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2011-09
- Volume
- 119
- Issue
- 1
- Pages
- 153-164
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- PMC
- PMC3171599
- OpenAlex
- W1543582830
- Cited by
- 37
- References
- 53
- Citations by year
- 2026: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 3 · 2017: 3 · 2016: 4 · 2015: 6 · 2014: 2 · 2013: 3 · 2012: 6
- FWCI
- 1.43
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Georgetown University
- National Institutes of Health
- National Institute on Drug Abuse (DA012976, U19DA027990, R01DA012976, R56DA012976, R01DA015767)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Keywords
- chronic nicotine, neuronal nicotinic acetylcholine receptors, receptor up-regulation, cell surface receptor expression, intracellular receptors, cortical neurons, hippocampal neurons, fetal rat brain
- MeSH terms
- Animals, Brain, Cells, Cultured, Cerebral Cortex, Cycloheximide, Female, Hippocampus, Methionine, Neurons, Nicotine, Pregnancy, Protein Synthesis Inhibitors, Pyridines, Receptors, Nicotinic, Up-Regulation, Nicotinic Agonists, Bridged Bicyclo Compounds, Heterocyclic, Biotinylation, Immunoprecipitation, Rats
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