+ Most Popular
Cunninghamia lanceolata plantations in China
Mammalian lairs in paleo ecological studies and palynology
Studies on technological possibilities in utilization of anhydrous milk fat for production of recombined butter-like products
Should right-sided fibroelastomas be operated upon?
Large esophageal lipoma
Apoptosis in the mammalian thymus during normal histogenesis and under various in vitro and in vivo experimental conditions
Poissons characoides nouveaux ou non signales de l'Ilha do Bananal, Bresil
Desensitizing efficacy of Colgate Sensitive Maximum Strength and Fresh Mint Sensodyne dentifrices
Administration of fluid by subcutaneous infusion: revival of a forgotten method
Tundra mosquito control - an impossible dream?
Schizophrenia for primary care providers: how to contribute to the care of a vulnerable patient population
Geochemical pattern analysis; method of describing the Southeastern limestone regional aquifer system
Incidence of low birth weights in a hospital of Mexico City
Graded management intensity of grassland systems for enhancing floristic diversity
Microbiology and biochemistry of cheese and fermented milk
The ember tetra: a new pygmy characid tetra from the Rio das Mortes, Brazil, Hyphessobrycon amandae sp. n. (Pisces, Characoidei)
Risk factors of contrast-induced nephropathy in patients after coronary artery intervention
Renovation of onsite domestic wastewater in a poorly drained soil
Observations of the propagation velocity and formation mechanism of burst fractures caused by gunshot
Systolic blood pressure in a population of infants in the first year of life: the Brompton study
Haematological studies in rats fed with metanil yellow
Studies on pasteurellosis. I. A new species of Pasteurella encountered in chronic fowl cholera
Dormancy breaking and germination of Acacia salicina Lindl. seeds
therapy of lupus nephritis. a two-year prospective study

Varenicline blocks β2*-nAChR-mediated response and activates β4*-nAChR-mediated responses in mice in vivo

Varenicline blocks β2*-nAChR-mediated response and activates β4*-nAChR-mediated responses in mice in vivo

Nicotine and Tobacco Research: Official Journal of the Society for Research on Nicotine and Tobacco 14(6): 711-719

ISSN/ISBN: 1462-2203

PMID: 22241831

DOI: 10.1093/ntr/ntr284

The smoking cessation aid, varenicline, has higher affinity for the alpha4beta2-subtype of the nicotinic acetylcholine receptor (α4β2*-nAChR) than for other subtypes of nAChRs by in vitro assays. The mechanism of action of acute varenicline was studied in vivo to determine (a) subtype activation associated with physiological effects and (b) dose relationship as an antagonist of nicotine. Acute doses of saline, nicotine, and varenicline were given to mice, and locomotor depression and hypothermia were measured. Subunit null mutant mice as well as selective antagonists were used to study mode of action of varenicline as an agonist. Varenicline as an antagonist of nicotine was also investigated. Varenicline evokes locomotor depression and hypothermia at higher doses than necessary for nicotine. Null mutation of the α7- or β2-nAChR subunit did not decrease the effectiveness of varenicline; however, null mutation of the β4 subunit significantly decreased the magnitude of the varenicline effect. Effects of the highest dose studied were blocked by mecamylamine (general nAChR antagonist) and partially antagonized by hexamethonium (largely peripheral nAChR antagonist). No significant block was seen with ondansetron antagonist of 5-hydroxytryptamine 3 receptor. Using a dose of nicotine selective for β2*-nAChR subtype effects with these tests, dose-dependent antagonism by varenicline was seen. Effective inhibitory doses were determined and appear to be in a range consistent with binding affinity or desensitization of β2*-nAChRs. Varenicline acts as a functional antagonist of β2*-nAChRs, blocking certain effects of nicotine. At higher doses, varenicline is an agonist of β4*-nAChRs producing physiological changes in mice.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 056845504

Download citation: RISBibTeXText

Related references

E-cigarette-Induced Pulmonary Inflammation and Dysregulated Repair are Mediated by nAChR α7 Receptor: Role of nAChR α7 in ACE2 Covid-19 receptor regulation. Research Square 2020, 2020

E-cigarette-induced pulmonary inflammation and dysregulated repair are mediated by nAChR α7 receptor: role of nAChR α7 in SARS-CoV-2 Covid-19 ACE2 receptor regulation. Respiratory Research 21(1): 154, 2020

Compensatory changes in nAChR channel expression following antisense oligonucleotide-mediated subunit deletion alpha-5 minus and alpha-7 minus nAChR channels. Society for Neuroscience Abstracts 21(1-3): 1333, 1995

NAChR-mediated calcium responses and plasticity in Drosophila Kenyon cells. Developmental Neurobiology 67(11): 1520-1532, 2007

Chronic treatment with varenicline changes expression of four nAChR binding sites in mice. Neuropharmacology 99: 142-155, 2015

Mechanism of YB-1-mediated translational induction of GluR2 mRNA in response to neural activity through nAChR. Biochimica et Biophysica Acta 1820(7): 1035-1042, 2012

α7 nAChR mediated Fas demethylation contributes to prenatal nicotine exposure-induced programmed thymocyte apoptosis in mice. Oncotarget 8(55): 93741-93756, 2017

JWX-A0108, a positive allosteric modulator of α7 nAChR, attenuates cognitive deficits in APP/PS1 mice by suppressing NF-κB-mediated inflammation. International Immunopharmacology 96: 107726, 2021

Nicotine-mediated activation of α2 nAChR-expressing OLM cells in developing mouse brains disrupts OLM cell-mediated control of LTP in adolescence. Neurobiology of Learning and Memory 2022: 107674, 2022

Gain of function mutants in human or mouse nAChR β3 subunits interchangeably activate either human or mouse α6β4*-nAChR, but not human or mouse α6β2*-nAChR. Biochemical Pharmacology 78(7): 901-902, 2009

Modulation of recombinant, α2*, α3* or α4*-nicotinic acetylcholine receptor (nAChR) function by nAChR β3 subunits. Journal of Neurochemistry 121(3): 349-361, 2012

Modulation of recombinant, α2*, α3* or α4*― nicotinic acetylcholine receptor (nAChR) function by nAChR β3 subunit. Journal of Neurochemistry 121(3-4): 349-361, 2012

Photolabeling a Nicotinic Acetylcholine Receptor (nAChR) with an (α4)3(β2)2 nAChR-Selective Positive Allosteric Modulator. Molecular Pharmacology 89(5): 575-584, 2016

Reporter mutation studies show that nicotinic acetylcholine receptor (nAChR) α5 Subunits and/or variants modulate function of α6*-nAChR. Journal of Biological Chemistry 286(44): 37905-37918, 2011

Potent Antiglioblastoma Agents by Hybridizing the Onium-Alkyloxy-Stilbene Based Structures of an α7-nAChR, α9-nAChR Antagonist and of a Pro-Oxidant Mitocan. Journal of Medicinal Chemistry 61(23): 10531-10544, 2018