ReviewThe AAPS journal2009
Nicotine is a selective pharmacological chaperone of acetylcholine receptor number and stoichiometry. Implications for drug discovery.
Review in The AAPS journal, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
98 citing papers in PubMed, 161 citations in OpenAlex.
- Treatment for tobacco dependence: effect on brain nicotinic acetylcholine receptor density.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2013Trial
- Naltrexone, Naloxone, Morphine, and Fentanyl Pharmacologically Chaperone a Mutant μ-Opioid Receptor via an Endoplasmic Reticulum Exit Site-Dependent Pathway.Pharmacology research & perspectives · 2026Article
- Precise mapping of a snake venom phospholipase AToxicon : official journal of the International Society on Toxinology · 2025Article
- Nicotine Attenuates Molecular Signalings in the BTBR TMolecular neurobiology · 2025Article
- Molecular insights into the α6β4 nicotinic acetylcholine receptor function and ligand recognition.Nature communications · 2025Article
- Simulating early steps in nicotine dependence: Pharmacokinetics, activation, and chaperoning of nicotinic receptors.Molecular pharmacology · 2025Article
- Abundant extrasynaptic expression of α3β4-containing nicotinic acetylcholine receptors in the medial habenula-interpeduncular nucleus pathway in mice.Scientific reports · 2024Article
- α4 nicotinic receptors on GABAergic neurons mediate a cholinergic analgesic circuit in the substantia nigra pars reticulata.Acta pharmacologica Sinica · 2024Article
- The many enigmas of nicotine.Advances in pharmacology (San Diego, Calif.) · 2024Review
- Antidepressants enter cells, organelles, and membranes.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Review
- Selective Serotonin Reuptake Inhibitors within Cells: Temporal Resolution in Cytoplasm, Endoplasmic Reticulum, and Membrane.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Potentiation of (α4)2(β2)3, but not (α4)3(β2)2, nicotinic acetylcholine receptors reduces nicotine self-administration and withdrawal symptoms.Neuropharmacology · 2021Article
- Smoking flies: testing the effect of tobacco cigarettes on heart function ofBiology open · 2021Article
- NACHO and 14-3-3 promote expression of distinct subunit stoichiometries of the α4β2 acetylcholine receptor.Cellular and molecular life sciences : CMLS · 2021Article
- Cholinergic Receptor Modulation as a Target for Preventing Dementia in Parkinson's Disease.Frontiers in neuroscience · 2021Review
- Multidimensional Intersection of Nicotine, Gene Expression, and Behavior.Frontiers in behavioral neuroscience · 2021Article
- Hair cell α9α10 nicotinic acetylcholine receptor functional expression regulated by ligand binding and deafness gene products.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The Impact of Electronic Nicotine Delivery System (ENDS) Flavors on Nicotinic Acetylcholine Receptors and Nicotine Addiction-Related Behaviors.Molecules (Basel, Switzerland) · 2020Review
- Article
- Nicotinic acetylcholine receptors: Conventional and unconventional ligands and signaling.Neuropharmacology · 2020Review
38 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
The acronym SePhaChARNS, for "selective pharmacological chaperoning of acetylcholine receptor number and stoichiometry," is introduced. We hypothesize that SePhaChARNS underlies classical observations that chronic exposure to nicotine causes "upregulation" of nicotinic receptors (nAChRs). If the hypothesis is proven, (1) SePhaChARNS is the molecular mechanism of the first step in neuroadaptation to chronic nicotine; and (2) nicotine addiction is partially a disease of excessive chaperoning. The chaperone is a pharmacological one, nicotine; and the chaperoned molecules are alpha4beta2* nAChRs. SePhaChARNS may also underlie two inadvertent therapeutic effects of tobacco use: (1) the inverse correlation between tobacco use and Parkinson's disease; and (2) the suppression of seizures by nicotine in autosomal dominant nocturnal frontal lobe epilepsy. SePhaChARNS arises from the thermodynamics of pharmacological chaperoning: ligand binding, especially at subunit interfaces, stabilizes AChRs during assembly and maturation, and this stabilization is most pronounced for the highest-affinity subunit compositions, stoichiometries, and functional states of receptors. Several chemical and pharmacokinetic characteristics render exogenous nicotine a more potent pharmacological chaperone than endogenous acetylcholine. SePhaChARNS is modified by desensitized states of nAChRs, by acid trapping of nicotine in organelles, and by other aspects of proteostasis. SePhaChARNS is selective at the cellular, and possibly subcellular, levels because of variations in the detailed nAChR subunit composition, as well as in expression of auxiliary proteins such as lynx. One important implication of the SePhaChARNS hypothesis is that therapeutically relevant nicotinic receptor drugs could be discovered by studying events in intracellular compartments rather than exclusively at the surface membrane.
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Registered trials
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.