Cited by 202Nicotinic Acetylcholine Receptors StudyNeuroscience and Neuropharmacology ResearchSmoking Behavior and Cessation

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Chronic Nicotine Exposure Upregulates Nicotinic Receptors by a Novel Mechanism

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Vallejo, Y. F.·2005·Journal of Neuroscience

DOI 10.1523/jneurosci.5240-04.2005PMC PMC2246082

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Abstract

Nicotine addiction is initiated by its binding to high-affinity nicotinic receptors in brain composed primarily of alpha4 and beta2 subunits. For nicotinic receptors expressed in vivo or heterologously, nicotine exposure over hours to days increases or "upregulates" high-affinity nicotine binding to receptors through a posttranslational mechanism thought to increase receptor numbers. Using heterologous expression, we find nicotine exposure causes a fourfold to sixfold higher binding to alpha4beta2 receptors that does not correspond with any significant change in the number of surface receptors or a change in the assembly, trafficking, or cell-surface turnover of the receptors. However, upregulation does alter the functional state of the receptor, slowing desensitization and enhancing sensitivity to acetylcholine. Based on these findings, we propose an alternative mechanism to explain nicotine-induced upregulation in which nicotine exposure slowly stabilizes alpha4beta2 receptors in a high-affinity state that is more easily activated, thereby providing a memory for nicotine exposure.

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Authors: Vallejo, Y. F.
Affiliations: University of Chicago (US)
Corresponding author: Vallejo, Y. F.
Venue: Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2005-06-08
Volume: 25
Issue: 23
Pages: 5563-5572
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.5240-04.2005
PMC: PMC2246082
OpenAlex: W2055762844
Cited by: 201
References: 58
Citations by year: 2025: 4 · 2024: 6 · 2023: 2 · 2022: 4 · 2021: 5 · 2020: 6 · 2018: 2 · 2017: 13 · 2016: 14 · 2015: 13 · 2014: 10 · 2013: 15 · 2012: 10
FWCI: 6.02
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Neuroscience (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Science Foundation
Brain Research Foundation
Alzheimer's Association
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
National Institutes of Health
National Institute on Drug Abuse (P01DA019695)
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 › Public Health, Environmental and Occupational Health › Smoking Behavior and Cessation
Keywords: nicotine, nicotinic acetylcholine receptors, alpha4beta2 receptor, receptor up-regulation, receptor desensitization, acetylcholine sensitivity, receptor stabilization, nicotine dependence, receptor trafficking, receptor turnover
MeSH terms: Cell Line, Humans, Nicotine, Radioligand Assay, Receptors, Nicotinic, Time Factors, Up-Regulation, Nicotinic Agonists, Biotinylation

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Chronic Nicotine Exposure Upregulates Nicotinic Receptors by a Novel Mechanism

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