The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
Chronic Nicotine Exposure Upregulates Nicotinic Receptors by a Novel Mechanism
Open accessAbstract
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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“It appears that the increased surface expression of nAChRs following chronic nicotine can indeed result in increased activation of nAChRs (Vallejo et al., 2005; Wonnacott, 1990), although the discrepancy between studies suggests that there is a dynamic equilibrium between activation and desensitization of nAChRs following chronic nicotine exposure.”
From It is not “either/or”: Activation and desensitization of nicotinic acetylcholine receptors both contribute to behaviors related to nicotine addiction and mood (2008) · cites this paper as Vallejo et al., 2005
Experimental — accuracy not yet measuredIn the citing paper
“Alternatively, or as well, nicotine exposure may slowly stabilize nAChRs in a high-affinity state that is more easily activated, leading eventually to desensitization (Vallejo et al., 2005).”
From Nicotinic receptor-mediated reduction in l-DOPA-induced dyskinesias may occur via desensitization (2010) · cites this paper as Vallejo et al., 2005
In the citing paper
“In previous studies on isolated cells, both agonists and antagonists can upregulate receptors (50,52,54,58,59).”
From Nicotine is a selective pharmacological chaperone of acetylcholine receptor number and stoichiometry. Implications for drug discovery (2009) · cites this paper as [52]
In the citing paper
“Descriptions that may be essentially equivalent to SePhaChARNS are the statements that nicotine acts as a “maturational enhancer” or a “novel slow stabilizer” for α4β2* receptors (39,50–52).”
From Nicotine is a selective pharmacological chaperone of acetylcholine receptor number and stoichiometry. Implications for drug discovery (2009) · cites this paper as [52]
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Cites
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Cited by
Sorted by citations
Mammalian nicotinic acetylcholine receptors: from structure to function
Albuquerque, E. X., Pereira, E. F. R., Alkondon, M., & Rogers, S. W. (2009) · Physiological Reviews · doi:10.1152/physrev.00015.2008 · Cited by 1,724
Nicotinic Acetylcholine Receptors and Nicotinic Cholinergic Mechanisms of the Central Nervous System
Dani, J. A., & Bertrand, D. (2007) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.47.120505.105214 · Cited by 1,197
PICCIOTTO, M., ADDY, N., MINEUR, Y., & BRUNZELL, D. (2008) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2007.12.005 · Cited by 460
Reward, addiction, withdrawal to nicotine
De Biasi, M., & Dani, J. A. (2011) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-061010-113734 · Cited by 366
Govind, A. P., Vezina, P., & Green, W. N. (2009) · Biochemical Pharmacology · doi:10.1016/j.bcp.2009.06.011 · Cited by 338
Metadata
- 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
- 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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