Up-regulation of Nicotinic Receptors by Nicotine Varies with Receptor Subtype
Open accessAbstract
Recent evidence suggests that in addition to alpha4beta2 and alpha3-containing nicotinic receptors, alpha6-containing receptors are present in midbrain dopaminergic neurons and involved in the nicotine reward pathway. Using heterologous expression, we found that alpha6beta2, like alpha3beta2 and alpha4beta2 receptors, formed high affinity epibatidine binding complexes that are pentameric, trafficked to the cell surface, and produced acetylcholine-evoked currents. Chronic nicotine exposure up-regulated alpha6beta2 receptors with differences in up-regulation time course and concentration dependence compared with alpha4beta2 receptors, the predominant high affinity nicotine binding site in brain. The alpha6beta2 receptor up-regulation required higher nicotine concentrations than for alpha4beta2 but lower than for alpha3beta2 receptors. The alpha6beta2 up-regulation occurred 10-fold faster than for alpha4beta2 and slightly faster than for alpha3beta2. Our data suggest that nicotinic receptor up-regulation is subtype-specific such that alpha6-containing receptors up-regulate in response to transient, high nicotine exposures, whereas sustained, low nicotine exposures up-regulate alpha4beta2 receptors.
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Evidence indicates that α4β2* nAChRs do not down-regulate in response to lasting cholinergic stimulation.
“Evidence indicating that α4β2* nAChRs do not down-regulate in response to lasting cholinergic stimulation (Walsh et al, 2008, Yates et al, 1995) is consistent with this assumption.”
From Modes and models of forebrain cholinergic neuromodulation of cognition (2011) · cites this paper as Walsh et al, 2008
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- Authors
- Walsh, H., Govind, A. P., Mastro, R., Hoda, J. C., Bertrand, D., Vallejo, Y., & Green, W. N.
- Affiliations
- University of Chicago (US)
- University of Geneva (CH)
- Corresponding author
- Green, William N.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2008-03
- Volume
- 283
- Issue
- 10
- Pages
- 6022-6032
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1997230575
- Cited by
- 87
- References
- 66
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 2 · 2019: 5 · 2018: 1 · 2017: 4 · 2016: 7 · 2015: 7 · 2014: 6 · 2013: 6 · 2012: 4
- FWCI
- 5.90
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- 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
- nicotinic acetylcholine receptors, nicotine, receptor up-regulation, alpha4beta2 receptor, receptor subtype specificity, epibatidine binding, acetylcholine-evoked currents, chronic nicotine exposure, midbrain dopaminergic neurons
- MeSH terms
- Animals, Cell Line, Ganglionic Stimulants, Mesencephalon, Nerve Tissue Proteins, Neurons, Nicotine, Receptors, Nicotinic, Time Factors, Up-Regulation, Protein Transport, Rats
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