ArticleNeuropharmacology2012
Use of an α3β4 nicotinic acetylcholine receptor subunit concatamer to characterize ganglionic receptor subtypes with specific subunit composition reveals species-specific pharmacologic properties.
Article in Neuropharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 34 citations in OpenAlex.
- An accessory orthosteric ligand binding site in the (α3)Cell reports · 2026Article
- Investigating the role of nicotinic acetylcholine receptors in menthol's effects in mice.Drug and alcohol dependence · 2024Article
- New Alpha9 nAChR Ligands Based on a 5-(Quinuclidin-3-ylmethyl)-1,2,4-oxadiazole Scaffold.ACS chemical neuroscience · 2024Article
- The many enigmas of nicotine.Advances in pharmacology (San Diego, Calif.) · 2024Review
- αFrontiers in neural circuits · 2021Article
- Nicotinic Acetylcholine Receptor Accessory Subunits Determine the Activity Profile of Epibatidine Derivatives.Molecular pharmacology · 2020Article
- Expression of α3β2β4 nicotinic acetylcholine receptors by rat adrenal chromaffin cells determined using novel conopeptide antagonists.Journal of neurochemistry · 2020Article
- Nicotinic Acetylcholine Receptor Signaling in the Hypothalamus: Mechanisms Related to Nicotine's Effects on Food Intake.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2020Review
- The α5 Nicotinic Acetylcholine Receptor Subunit Differentially Modulates α4β2Frontiers in synaptic neuroscience · 2020Review
- New insights on the effects of varenicline on nicotine reward, withdrawal and hyperalgesia in mice.Neuropharmacology · 2018Article
- Molecular and cellular characterization of nicotinic acetylcholine receptor subtypes in the arcuate nucleus of the mouse hypothalamus.The European journal of neuroscience · 2018Article
- Nicotinic acetylcholine receptors in neuropathic and inflammatory pain.FEBS letters · 2018Review
- Human nicotinic receptors in chromaffin cells: characterization and pharmacology.Pflugers Archiv : European journal of physiology · 2018Review
- Therapeutic concentrations of varenicline in the presence of nicotine increase action potential firing in human adrenal chromaffin cells.Journal of neurochemistry · 2017Article
- AT-1001 Is a Partial Agonist with High Affinity and Selectivity at Human and Rat α3β4 Nicotinic Cholinergic Receptors.Molecular pharmacology · 2015Article
- Nicotinic receptors in non-human primates: Analysis of genetic and functional conservation with humans.Neuropharmacology · 2015Review
- Enantiopure Cyclopropane-Bearing Pyridyldiazabicyclo[3.3.0]octanes as Selective α4β2-nAChR Ligands.ACS medicinal chemistry letters · 2014Article
- The minimal pharmacophore for silent agonism of the α7 nicotinic acetylcholine receptor.The Journal of pharmacology and experimental therapeutics · 2014Article
- The novel α7β2-nicotinic acetylcholine receptor subtype is expressed in mouse and human basal forebrain: biochemical and pharmacological characterization.Molecular pharmacology · 2014Article
- Varenicline and cytisine diminish the dysphoric-like state associated with spontaneous nicotine withdrawal in rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2014Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Drug development for nicotinic acetylcholine receptors (nAChR) is challenged by subtype diversity arising from variations in subunit composition. On-target activity for neuronal heteromeric receptors is typically associated with CNS receptors that contain α4 and other subunits, while off-target activity could be associated with ganglionic-type receptors containing α3β4 binding sites and other subunits, including β4, β2, α5, or α3 as a structural subunit in the pentamer. Additional interest in α3 β4 α5-containing receptors arises from genome-wide association studies linking these genes, and a single nucleotide polymorphism (SNP) in α5 in particular, to lung cancer and heavy smoking. While α3 and β4 readily form receptors in expression system such as the Xenopus oocyte, since α5 is not required for function, simple co-expression approaches may under-represent α5-containing receptors. We used a concatamer of human α3 and β4 subunits to form ligand-binding domains, and show that we can force the insertions of alternative structural subunits into the functional pentamers. These α3β4 variants differ in sensitivity to ACh, nicotine, varenicline, and cytisine. Our data indicated lower efficacy for varenicline and cytisine than expected for β4-containing receptors, based on previous studies of rodent receptors. We confirm that these therapeutically important α4 receptor partial agonists may present different autonomic-based side-effect profiles in humans than will be seen in rodent models, with varenicline being more potent for human than rat receptors and cytisine less potent. Our initial characterizations failed to find functional effects of the α5 SNP. However, our data validate this approach for further investigations.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.