ArticleThe Journal of biological chemistry2015
An Accessory Agonist Binding Site Promotes Activation of α4β2* Nicotinic Acetylcholine Receptors.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 42 citations in OpenAlex.
- An accessory orthosteric ligand binding site in the (α3)Cell reports · 2026Article
- Functions and pharmacology of α2β2 nicotinic acetylcholine receptors; in and out of the shadow of α4β2 nicotinic acetylcholine receptors.Biochemical pharmacology · 2024Article
- SR9883 is a novel small-molecule enhancer of α4β2* nicotinic acetylcholine receptor signaling that decreases intravenous nicotine self-administration in rats.Frontiers in molecular neuroscience · 2024Article
- Insights Into the Differential Desensitization ofMolecular pharmacology · 2023Article
- The α9α10 nicotinic acetylcholine receptor: a compelling drug target for hearing loss?Expert opinion on therapeutic targets · 2022Review
- Neurobiological Mechanisms of Nicotine Reward and Aversion.Pharmacological reviews · 2022Review
- Article
- The Impact of Electronic Nicotine Delivery System (ENDS) Flavors on Nicotinic Acetylcholine Receptors and Nicotine Addiction-Related Behaviors.Molecules (Basel, Switzerland) · 2020Review
- Activation of Somatostatin Interneurons by Nicotinic Modulator Lypd6 Enhances Plasticity and Functional Recovery in the Adult Mouse Visual Cortex.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Dynamics and Interactions of GPI-Linked lynx1 Protein with/without Nicotinic Acetylcholine Receptor in Membrane Bilayers.The journal of physical chemistry. B · 2020Article
- Nicotinic acetylcholine receptors: Conventional and unconventional ligands and signaling.Neuropharmacology · 2020Review
- Promoting activity of (α4)Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2020Article
- Discovery of an intrasubunit nicotinic acetylcholine receptor-binding site for the positive allosteric modulator Br-PBTC.The Journal of biological chemistry · 2019Article
- The fifth subunit of the (α4β2)British journal of pharmacology · 2018Article
- Orthosteric and allosteric potentiation of heteromeric neuronal nicotinic acetylcholine receptors.British journal of pharmacology · 2018Review
- Stoichiometry of the Heteromeric Nicotinic Receptors of the Renshaw Cell.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- The nicotinic receptor drug sazetidine-A reduces alcohol consumption in mice without affecting concurrent nicotine consumption.Neuropharmacology · 2018Article
- Nicotinic acetylcholine receptors in neuropathic and inflammatory pain.FEBS letters · 2018Review
- Neuronal and Extraneuronal Nicotinic Acetylcholine Receptors.Current neuropharmacology · 2018Review
- The (Molecular pharmacology · 2017Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Neuronal nicotinic acetylcholine receptors containing α4, β2, and sometimes other subunits (α4β2* nAChRs) regulate addictive and other behavioral effects of nicotine. These nAChRs exist in several stoichiometries, typically with two high affinity acetylcholine (ACh) binding sites at the interface of α4 and β2 subunits and a fifth accessory subunit. A third low affinity ACh binding site is formed when this accessory subunit is α4 but not if it is β2. Agonists selective for the accessory ACh site, such as 3-[3-(3-pyridyl)-1,2,4-oxadiazol-5-yl]benzonitrile (NS9283), cannot alone activate a nAChR but can facilitate more efficient activation in combination with agonists at the canonical α4β2 sites. We therefore suggest categorizing agonists according to their site selectivity. NS9283 binds to the accessory ACh binding site; thus it is termed an accessory site-selective agonist. We expressed (α4β2)2 concatamers in Xenopus oocytes with free accessory subunits to obtain defined nAChR stoichiometries and α4/accessory subunit interfaces. We show that α2, α3, α4, and α6 accessory subunits can form binding sites for ACh and NS9283 at interfaces with α4 subunits, but β2 and β4 accessory subunits cannot. To permit selective blockage of the accessory site, α4 threonine 126 located on the minus side of α4 that contributes to the accessory site, but not the α4β2 sites, was mutated to cysteine. Alkylation of this cysteine with a thioreactive reagent blocked activity of ACh and NS9283 at the accessory site. Accessory agonist binding sites are promising drug targets.
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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.