A subtype of nicotinic cholinergic receptor in rat brain is composed of alpha 4 and beta 2 subunits and is up-regulated by chronic nicotine treatment.

Flores, C M; Rogers, S W; Pabreza, L A; Wolfe, B B; Kellar, K J

doi:10.1016/s0026-895x(25)08832-7

Cited by 880Nicotinic Acetylcholine Receptors StudyNeuroscience and Neuropharmacology ResearchSmoking Behavior and Cessation

A subtype of nicotinic cholinergic receptor in rat brain is composed of alpha 4 and beta 2 subunits and is up-regulated by chronic nicotine treatment.

Flores, C M, Rogers, S W, Pabreza, L A, Wolfe, B B, Kellar, K J·1992·Molecular Pharmacology

DOI 10.1016/s0026-895x(25)08832-7

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Abstract

The subunit composition and pharmacological regulation of rat neuronal nicotinic cholinergic receptors were assessed. Specific immunoprecipitation was determined in solubilized rat brain homogenates using [3H]cytisine, a high affinity agonist at nicotinic receptors, in conjunction with polyclonal antisera generated against nonhomologous domains of the various subunits comprising this receptor class. In all brain regions tested, only antisera generated against the alpha 4 and beta 2 subunits were able to immunoprecipitate specifically receptors labeled by [3H]cytisine. Thus, these sera were further characterized in order to validate and optimize their use in the immunoprecipitation protocol. Preincubation of solubilized receptors from rat forebrain with antisera generated against the alpha 2, alpha 3, alpha 5, beta 3, or beta 4 subunits did not decrease the amount of precipitable alpha 4 or beta 2 subunit. On the other hand, when either anti-alpha 4 or anti-beta 2 serum was used to immunoprecipitate solubilized receptors from rat forebrain, the supernatants contained little if any remaining receptors that could be specifically precipitated by either antibody. Because these antisera do not cross-react, the data indicate that alpha 4 and beta 2 subunits are associated with each other in at least one neuronal nicotinic receptor subtype that has high affinity for agonists. Moreover, these results imply that all alpha 4 subunits that are labeled by [3H]cystisine are coupled to beta 2 subunits. We also present evidence that the alpha 4/beta 2 subtype characterized in this report is significantly increased in the cortex of rats chronically treated with nicotine.

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Nicotine-induced increases in nAChR (upregulation) are conferred by a specific microdomain in the β2-subunit and are confined to nAChRs that contain the β2-subunit.
“Importantly, nicotine induced increases in nAChR, termed “upregulation”, are conferred by a specific microdomain that is in the β2-subunit 34 and thus this upregulation is confined to nAChR that contain the β2-subunit4, 19, 31, 35-38.”
From β2-Nicotinic Acetylcholine Receptor Availability During Acute and Prolonged Abstinence From Tobacco Smoking (2009) · cites this paper as [19]
Chronic nicotine administration increases predominantly the α4β2 subtype of nAChRs in rodent brain.
“Immunoprecipitation with subunit-selective antibodies and studies in genetic knockout models demonstrate that chronic administration of nicotine increases predominantly the ␣4␤2 subtype of nAChRs in rodent brain (Flores et al., 1992;Mao et al., 2008;Moretti et al., 2010;Marks et al., 2011)”
From Chronic Sazetidine-A at Behaviorally Active Doses Does Not Increase Nicotinic Cholinergic Receptors in Rodent Brain (2012) · cites this paper as Flores et al., 1992

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MOLECULAR PHARMACOLOGY, 41:31-37 A Subtype of Nicotinic Cholinergic Receptor in Rat Brain Is Composed of a4 and 32 Subunits and Is Up-regulated by Chronic Nicotine Treatment
Flores, C. M., Rogers, S. W., Pabreza, L. A., Wolfe, B. B., & Kellar, K. J. (1991)
The α4β2α5 nicotinic cholinergic receptor in rat brain is resistant to up‐regulation by nicotine<i>in vivo</i>
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Roles of nicotinic acetylcholine receptor β subunits in function of human α4‐containing nicotinic receptors
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Authors: Flores, C. M., Rogers, S. W., Pabreza, L. A., Wolfe, B. B., & Kellar, K. J.
Affiliations: Georgetown University Medical Center (US)
University of Colorado Denver (US)
Georgetown University (US)
ORCID: Kellar, K J
Venue: Molecular Pharmacology
Publisher: Elsevier BV
Published: 1992-01
Volume: 41
Issue: 1
Pages: 31-37
ISSN: 0026-895X (ISSN-L)
DOI: 10.1016/s0026-895x(25)08832-7
OpenAlex: W2116249462
Cited by: 880
References: 0
Citations by year: 2026: 2 · 2025: 1 · 2024: 3 · 2023: 3 · 2022: 7 · 2021: 7 · 2020: 7 · 2019: 10 · 2018: 7 · 2017: 9 · 2016: 18 · 2015: 25 · 2014: 25 · 2013: 22 · 2012: 21
FWCI: 8.73
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Molecular Pharmacology (publishedVersion)
PubMed (publishedVersion)
PubMed
Funders: National Institutes of Health (5r01ag009884-05, 5r01da006486-10, 5r01ns011549-24)
National Institute on Aging (AG 09884)
National Institute on Drug Abuse (DA-06486)
National Institute of Neurological Disorders and Stroke (NS11549)
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, receptor subunit composition, chronic nicotine treatment, receptor up-regulation, rat cortex, forebrain, neuronal nicotinic receptors
MeSH terms: Quinolizidine Alkaloids, Alkaloids, Animals, Antibodies, Azocines, Brain, Kinetics, Male, Nicotine, Precipitin Tests, Quinolizines, Rats, Inbred Strains, Receptors, Nicotinic, Time Factors, Tritium, Up-Regulation, Macromolecular Substances, Rats

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A subtype of nicotinic cholinergic receptor in rat brain is composed of alpha 4 and beta 2 subunits and is up-regulated by chronic nicotine treatment.

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