ArticleBiochemical pharmacology2007
Cell autonomy, receptor autonomy, and thermodynamics in nicotine receptor up-regulation.
Article in Biochemical pharmacology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 42 citations in OpenAlex.
- Cholinergic modulation of hippocampal CA1 pyramidal cell excitability in ArxExperimental neurology · 2026Article
- α4 nicotinic receptors on GABAergic neurons mediate a cholinergic analgesic circuit in the substantia nigra pars reticulata.Acta pharmacologica Sinica · 2024Article
- Addiction-related neuroadaptations following chronic nicotine exposure.Journal of neurochemistry · 2021Review
- Neural circuits and nicotinic acetylcholine receptors mediate the cholinergic regulation of midbrain dopaminergic neurons and nicotine dependence.Acta pharmacologica Sinica · 2020Review
- Chronic Menthol Does Not Change Stoichiometry or Functional Plasma Membrane Levels of MouseMolecular pharmacology · 2019Article
- Video-assisted topographical measurement of cigarette smoking: Exploration of an objective approach to evaluate nicotine dependence.Tobacco prevention & cessation · 2018Article
- Expression profile of nicotinic acetylcholine receptor subunits in the brain of HIV-1 transgenic rats given chronic nicotine treatment.Journal of neurovirology · 2016Article
- Inside-out neuropharmacology of nicotinic drugs.Neuropharmacology · 2015Review
- Pharmacological chaperoning: a primer on mechanism and pharmacology.Pharmacological research · 2014Review
- Role of α6 nicotinic receptors in CNS dopaminergic function: relevance to addiction and neurological disorders.Biochemical pharmacology · 2011Review
- 86Rb+ efflux mediated by alpha4beta2*-nicotinic acetylcholine receptors with high and low-sensitivity to stimulation by acetylcholine display similar agonist-induced desensitization.Biochemical pharmacology · 2010Article
- Neonatal intermittent hypoxia impairs neuronal nicotinic receptor expression and function in adrenal chromaffin cells.American journal of physiology. Cell physiology · 2010Article
- Heterogeneity of reward mechanisms.Neurochemical research · 2010Review
- Nicotine response genetics in the zebrafish.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
- Risk for nicotine dependence and lung cancer is conferred by mRNA expression levels and amino acid change in CHRNA5.Human molecular genetics · 2009Article
- Cellular events in nicotine addiction.Seminars in cell & developmental biology · 2009Review
- Nicotine normalizes intracellular subunit stoichiometry of nicotinic receptors carrying mutations linked to autosomal dominant nocturnal frontal lobe epilepsy.Molecular pharmacology · 2009Article
- Nicotine is a selective pharmacological chaperone of acetylcholine receptor number and stoichiometry. Implications for drug discovery.The AAPS journal · 2009Review
- Structural answers and persistent questions about how nicotinic receptors work.Frontiers in bioscience : a journal and virtual library · 2008Review
- Chronic nicotine cell specifically upregulates functional alpha 4* nicotinic receptors: basis for both tolerance in midbrain and enhanced long-term potentiation in perforant path.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2007Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Chronic nicotine exposure, in smokers or in experimental rodents administered nicotine, produces elevated levels of nicotinic acetylcholine receptors in several brain regions. However, there are few data on up-regulation of receptors in specific neuronal subtypes. We tested whether functional up-regulation of nicotinic responses occurs in cultured GABAergic neurons of the ventral midbrain. Fura-2 measurements of nicotinic responses were made on ventral midbrain neurons from knock-in mice heterozygous for the alpha4-M2 domain Leu9'Ala mutation, which confers nicotine hypersensitivity. Chronic nicotine exposure at a concentration (10 nM for 3 days) that activates only the hypersensitive alpha4* (Leu9'Ala) receptors, but not wild-type receptors, resulted in significant potentiation of ACh (100 microM)-elicited responses. Experiments were also performed on midbrain neuronal cultures heterozygous for the alpha4* (Leu9'Ala) mutation as well as for a GFP protein fused to a GABA transporter that reliably reveals GABAergic neurons. In cultures chronically treated with 10nM nicotine, there was significantly increased alpha4* nicotinic-induced Ca(2+) influx elicited by low concentration of ACh (3 microM). Furthermore, chronic exposure to the competitive antagonist dihydro-beta-erythroidine, but not to the noncompetitive antagonist mecamylamine, induced up-regulation of ACh elicited nicotinic responses. These results suggest that occupation of alpha4* nicotinic receptor binding site(s), at the interface between two subunits, is sufficient to promote assembly and/or up-regulation of functional receptors in GABAergic neurons. Up-regulation in neurons is both "cell-autonomous", occurring at the cell itself, and "receptor autonomous", occurring at the receptor itself, and may be a thermodynamic necessity of ligand-protein interactions.
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Registered trials
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