Nicotinic alpha5 subunit deletion locally reduces high-affinity agonist activation without altering nicotinic receptor numbers.
paper
Cited
Public
Unavailable
- Authors
- Brown, Robert W B; Collins, Allan C; Lindstrom, Jon M; Whiteaker, Paul
- Year
- 2007
- Journal
- Journal of neurochemistry
- PMID
- 17573823
- DOI
- 10.1111/j.1471-4159.2007.04700.x
Neuronal nicotinic acetylcholine receptor subunit alpha5 mRNA is widely expressed in the CNS. An alpha5 gene polymorphism has been implicated in behavioral differences between mouse strains, and alpha5-null mutation induces profound changes in mouse acute responses to nicotine. In this study, we have examined the distribution and prevalence of alpha5* nicotinic acetylcholine receptor in mouse brain, and quantified the effects of alpha5-null mutation on pre-synaptic nicotinic acetylcholine receptor function (measured using synaptosomal (86)Rb(+) efflux) and overall [(125)I]epibatidine binding site expression. alpha5* nicotinic acetylcholine receptor expression was found in nine of fifteen regions examined, although < 20% of the total nicotinic acetylcholine receptor population in any region contained alpha5. Deletion of the alpha5 subunit gene resulted in localized loss of function (thalamus, striatum), which was itself confined to the DHbetaE-sensitive receptor population. No changes in receptor expression were seen. Consequently, functional changes must occur as a result of altered function per unit of receptor. The selective depletion of high agonist activation affinity sites results in overall nicotinic function being reduced, and increases the overall agonist activation affinity. Together, these results describe the receptor-level changes underlying altered behavioral responses to nicotine in nicotinic acetylcholine receptor alpha5 subunit-null mutants.
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| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
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| Linking altered neuronal and synaptic properties to nicotinic receptor Alpha5 subunit gene dysfunction: a translational investigation in rat mPFC and human cortical layer 6. | Yang D et al. | β | 2025 | β |
| Distinct Chrna5 mutations link excessive alcohol use to types I/II vulnerability profiles and IPN GABAergic neurons. | Tochon L et al. | β | 2024 | β |
| Contribution of the Ξ±5 nAChR Subunit and Ξ±5SNP to Nicotine-Induced Proliferation and Migration of Human Cancer Cells. | Papapostolou I et al. | β | 2023 | β |
| Discoveries and future significance of research into amyloid-beta/Ξ±7-containing nicotinic acetylcholine receptor (nAChR) interactions. | Whiteaker P et al. | β | 2023 | β |
| Linking the CHRNA5 SNP to drug abuse liability: From circuitry to cellular mechanisms. | Brynildsen JK et al. | β | 2021 | β |
| The Hair Cell Ξ±9Ξ±10 Nicotinic Acetylcholine Receptor: Odd Cousin in an Old Family. | Lipovsek M et al. | β | 2021 | β |
| A Review of the Cholinergic System and Therapeutic Approaches to Treat Brain Disorders. | Bertrand D et al. | β | 2020 | β |
| Behavioral and Molecular Basis of Cholinergic Modulation of Pain: Focus on Nicotinic Acetylcholine Receptors. | Toma W et al. | β | 2020 | β |
| Low-Dose Nicotine Activates EGFR Signaling via Ξ±5-nAChR and Promotes Lung Adenocarcinoma Progression. | Wang ML et al. | β | 2020 | β |
| More than Smoke and Patches: The Quest for Pharmacotherapies to Treat Tobacco Use Disorder. | Moerke MJ et al. | β | 2020 | β |
| Neurochemical organization of the ventral striatum's olfactory tubercle. | Cansler HL et al. | β | 2020 | β |
| Partial and full deletion of nicotinic acetylcholine receptor Ξ±4 and Ξ²2 subunits reduces sensitivity to acute nicotine administration and development of tolerance following chronic nicotine administration. | Marks MJ et al. | β | 2020 | β |
| The Ξ±5 Nicotinic Acetylcholine Receptor Subunit Differentially Modulates Ξ±4Ξ²2<sup>*</sup> and Ξ±3Ξ²4<sup>*</sup> Receptors. | Scholze P et al. | β | 2020 | β |
| Molecular mechanisms for nicotine intoxication. | Alkam T et al. | β | 2019 | β |
| Insights Into Nicotinic Receptor Signaling in Nicotine Addiction: Implications for Prevention and Treatment. | Liu W et al. | β | 2018 | β |
| Knockout of alpha 5 nicotinic acetylcholine receptors subunit alters ethanol-mediated behavioral effects and reward in mice. | Dawson A et al. | β | 2018 | β |
| Mutation Linked to Autosomal Dominant Nocturnal Frontal Lobe Epilepsy Reduces Low-Sensitivity Ξ±4Ξ²2, and Increases Ξ±5Ξ±4Ξ²2, Nicotinic Receptor Surface Expression. | Nichols WA et al. | β | 2016 | β |
| Nicotinic modulation of hippocampal cell signaling and associated effects on learning and memory. | Kutlu MG et al. | β | 2016 | β |
| Unorthodox Acetylcholine Binding Sites Formed by Ξ±5 and Ξ²3 Accessory Subunits in Ξ±4Ξ²2* Nicotinic Acetylcholine Receptors. | Jain A et al. | β | 2016 | β |
| Genetic variation (CHRNA5), medication (combination nicotine replacement therapy vs. varenicline), and smoking cessation. | Chen LS et al. | β | 2015 | β |
| Inside-out neuropharmacology of nicotinic drugs. | Henderson BJ et al. | β | 2015 | β |
| Natural genetic variability of the neuronal nicotinic acetylcholine receptor subunit genes in mice: Consequences and confounds. | Wilking JA et al. | β | 2015 | β |
| Regulation of Ξ±4Ξ²2Ξ±5 nicotinic acetylcholinergic receptors in rat cerebral cortex in early and late adolescence: Sex differences in response to chronic nicotine. | Hoegberg BG et al. | β | 2015 | β |
| Targeting Ξ±4Ξ²2 nicotinic acetylcholine receptors in central nervous system disorders: perspectives on positive allosteric modulation as a therapeutic approach. | Grupe M et al. | β | 2015 | β |
| The role of alpha5 nicotinic acetylcholine receptors in mouse models of chronic inflammatory and neuropathic pain. | Bagdas D et al. | β | 2015 | β |
| Ξ±-Conotoxins Identify the Ξ±3Ξ²4* Subtype as the Predominant Nicotinic Acetylcholine Receptor Expressed in Human Adrenal Chromaffin Cells. | Hone AJ et al. | β | 2015 | β |
| Effectiveness of nicotinic agonists as desensitizers at presynaptic Ξ±4Ξ²2- and Ξ±4Ξ±5Ξ²2-nicotinic acetylcholine receptors. | Wageman CR et al. | β | 2014 | β |
| Nicotinic acetylcholine receptors control acetylcholine and noradrenaline release in the rodent habenulo-interpeduncular complex. | Beiranvand F et al. | β | 2014 | β |
| Nicotinic acetylcholine receptors in attention circuitry: the role of layer VI neurons of prefrontal cortex. | Proulx E et al. | β | 2014 | β |
| Presynaptic GABAB autoreceptor regulation of nicotinic acetylcholine receptor mediated [(3)H]-GABA release from mouse synaptosomes. | McClure-Begley TD et al. | β | 2014 | β |
| Roles for N-terminal extracellular domains of nicotinic acetylcholine receptor (nAChR) Ξ²3 subunits in enhanced functional expression of mouse Ξ±6Ξ²2Ξ²3- and Ξ±6Ξ²4Ξ²3-nAChRs. | Dash B et al. | β | 2014 | β |
| The nicotinic Ξ±5 subunit can replace either an acetylcholine-binding or nonbinding subunit in the Ξ±4Ξ²2* neuronal nicotinic receptor. | Jin X et al. | β | 2014 | β |
| The Ξ±5 subunit regulates the expression and function of Ξ±4*-containing neuronal nicotinic acetylcholine receptors in the ventral-tegmental area. | Chatterjee S et al. | β | 2013 | β |
| Allosteric modulators of Ξ±4Ξ²2 nicotinic acetylcholine receptors: a new direction for antidepressant drug discovery. | Mantione E et al. | β | 2012 | β |
| Analgesic effects mediated by neuronal nicotinic acetylcholine receptor agonists: correlation with desensitization of Ξ±4Ξ²2* receptors. | Zhang J et al. | β | 2012 | β |
| Function of human Ξ±3Ξ²4Ξ±5 nicotinic acetylcholine receptors is reduced by the Ξ±5(D398N) variant. | George AA et al. | β | 2012 | β |
| Low concentrations of nicotine differentially desensitize nicotinic acetylcholine receptors that include Ξ±5 or Ξ±6 subunits and that mediate synaptosomal neurotransmitter release. | Grady SR et al. | β | 2012 | β |
| Nicotinic Ξ±5 subunits drive developmental changes in the activation and morphology of prefrontal cortex layer VI neurons. | Bailey CD et al. | β | 2012 | β |
| Acetylcholine receptor (AChR) Ξ±5 subunit variant associated with risk for nicotine dependence and lung cancer reduces (Ξ±4Ξ²2)βΞ±5 AChR function. | Kuryatov A et al. | β | 2011 | β |
| An autoradiographic survey of mouse brain nicotinic acetylcholine receptors defined by null mutants. | Baddick CG et al. | β | 2011 | β |
| Functional characterization of the Ξ±5(Asn398) variant associated with risk for nicotine dependence in the Ξ±3Ξ²4Ξ±5 nicotinic receptor. | Li P et al. | β | 2011 | β |
| Habenular Ξ±5 nicotinic receptor subunit signalling controls nicotine intake. | Fowler CD et al. | β | 2011 | β |
| Increased nicotinic acetylcholine receptor protein underlies chronic nicotine-induced up-regulation of nicotinic agonist binding sites in mouse brain. | Marks MJ et al. | β | 2011 | β |
| Reporter mutation studies show that nicotinic acetylcholine receptor (nAChR) Ξ±5 Subunits and/or variants modulate function of Ξ±6*-nAChR. | Dash B et al. | β | 2011 | β |
| 86Rb+ efflux mediated by alpha4beta2*-nicotinic acetylcholine receptors with high and low-sensitivity to stimulation by acetylcholine display similar agonist-induced desensitization. | Marks MJ et al. | β | 2010 | β |
| Cholinergic modulation of locomotion and striatal dopamine release is mediated by alpha6alpha4* nicotinic acetylcholine receptors. | Drenan RM et al. | β | 2010 | β |
| Chrna4 A529 knock-in mice exhibit altered nicotine sensitivity. | Wilking JA et al. | β | 2010 | β |
| Cortico-thalamic connectivity is vulnerable to nicotine exposure during early postnatal development through Ξ±4/Ξ²2/Ξ±5 nicotinic acetylcholine receptors. | Heath CJ et al. | β | 2010 | β |
| John Daly's compound, epibatidine, facilitates identification of nicotinic receptor subtypes. | Marks MJ et al. | β | 2010 | β |
| Mouse striatal dopamine nerve terminals express alpha4alpha5beta2 and two stoichiometric forms of alpha4beta2*-nicotinic acetylcholine receptors. | Grady SR et al. | β | 2010 | β |
| Role of alpha5 nicotinic acetylcholine receptors in pharmacological and behavioral effects of nicotine in mice. | Jackson KJ et al. | β | 2010 | β |
| The nicotinic acetylcholine receptor alpha5 subunit plays a key role in attention circuitry and accuracy. | Bailey CD et al. | β | 2010 | β |
| Acetylcholine-stimulated [3H]GABA release from mouse brain synaptosomes is modulated by alpha4beta2 and alpha4alpha5beta2 nicotinic receptor subtypes. | McClure-Begley TD et al. | β | 2009 | β |
| Diversity of vertebrate nicotinic acetylcholine receptors. | Millar NS et al. | β | 2009 | β |
| Nicotine is a selective pharmacological chaperone of acetylcholine receptor number and stoichiometry. Implications for drug discovery. | Lester HA et al. | β | 2009 | β |
| Pharmacological and immunochemical characterization of alpha2* nicotinic acetylcholine receptors (nAChRs) in mouse brain. | Whiteaker P et al. | β | 2009 | β |
| Prominent role of alpha3/alpha6beta2* nAChRs in regulating evoked dopamine release in primate putamen: effect of long-term nicotine treatment. | Perez XA et al. | β | 2009 | β |
| Risk for nicotine dependence and lung cancer is conferred by mRNA expression levels and amino acid change in CHRNA5. | Wang JC et al. | β | 2009 | β |
| Selectivity of ABT-089 for alpha4beta2* and alpha6beta2* nicotinic acetylcholine receptors in brain. | Marks MJ et al. | β | 2009 | β |
| Structural and functional diversity of native brain neuronal nicotinic receptors. | Gotti C et al. | β | 2009 | β |
| The road to discovery of neuronal nicotinic cholinergic receptor subtypes. | Collins AC et al. | β | 2009 | β |
| A candidate gene approach identifies the CHRNA5-A3-B4 region as a risk factor for age-dependent nicotine addiction. | Weiss RB et al. | β | 2008 | β |
| Developmental excitation of corticothalamic neurons by nicotinic acetylcholine receptors. | Kassam SM et al. | β | 2008 | β |
| Partial deletion of the nicotinic cholinergic receptor alpha 4 or beta 2 subunit genes changes the acetylcholine sensitivity of receptor-mediated 86Rb+ efflux in cortex and thalamus and alters relative expression of alpha 4 and beta 2 subunits. | Gotti C et al. | β | 2008 | β |
| Roles of accessory subunits in alpha4beta2(*) nicotinic receptors. | Kuryatov A et al. | β | 2008 | β |
| The subtypes of nicotinic acetylcholine receptors on dopaminergic terminals of mouse striatum. | Grady SR et al. | β | 2007 | β |