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The novel α7β2-nicotinic acetylcholine receptor subtype is expressed in mouse and human basal forebrain: biochemical and pharmacological characterization.
Moretti M
,
Zoli M
,
George AA
,
Lukas RJ
,
Pistillo F
,
Maskos U
,
Whiteaker P
,
Gotti C
.
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We examined α7β2-nicotinic acetylcholine receptor (α7β2-nAChR) expression in mammalian brain and compared pharmacological profiles of homomeric α7-nAChRs and α7β2-nAChRs. α-Bungarotoxin affinity purification or immunoprecipitation with anti-α7 subunit antibodies (Abs) was used to isolate nAChRs containing α7 subunits from mouse or human brain samples. α7β2-nAChRs were detected in forebrain, but not other tested regions, from both species, based on Western blot analysis of isolates using β2 subunit-specific Abs. Ab specificity was confirmed in control studies using subunit-null mutant mice or cell lines heterologously expressing specific human nAChR subtypes and subunits. Functional expression in Xenopus oocytes of concatenated pentameric (α7)5-, (α7)4(β2)1-, and (α7)3(β2)2-nAChRs was confirmed using two-electrode voltage clamp recording of responses to nicotinic ligands. Importantly, pharmacological profiles were indistinguishable for concatenated (α7)5-nAChRs or for homomeric α7-nAChRs constituted from unlinked α7 subunits. Pharmacological profiles were similar for (α7)5-, (α7)4(β2)1-, and (α7)3(β2)2-nAChRs except for diminished efficacy of nicotine (normalized to acetylcholine efficacy) at α7β2- versus α7-nAChRs. This study represents the first direct confirmation of α7β2-nAChR expression in human and mouse forebrain, supporting previous mouse studies that suggested relevance of α7β2-nAChRs in Alzheimer disease etiopathogenesis. These data also indicate that α7β2-nAChR subunit isoforms with different α7/β2 subunit ratios have similar pharmacological profiles to each other and to α7 homopentameric nAChRs. This supports the hypothesis that α7β2-nAChR agonist activation predominantly or entirely reflects binding to α7/α7 subunit interface sites.
Albuquerque,
Properties of neuronal nicotinic acetylcholine receptors: pharmacological characterization and modulation of synaptic function.
1997, Pubmed
Albuquerque,
Properties of neuronal nicotinic acetylcholine receptors: pharmacological characterization and modulation of synaptic function.
1997,
Pubmed
Albuquerque,
Mammalian nicotinic acetylcholine receptors: from structure to function.
2009,
Pubmed
Alkondon,
Choline is a selective agonist of alpha7 nicotinic acetylcholine receptors in the rat brain neurons.
1997,
Pubmed
Andersen,
Stoichiometry for activation of neuronal α7 nicotinic receptors.
2013,
Pubmed
Azam,
Co-expression of alpha7 and beta2 nicotinic acetylcholine receptor subunit mRNAs within rat brain cholinergic neurons.
2003,
Pubmed
Balestra,
Chick optic lobe contains a developmentally regulated alpha2alpha5beta2 nicotinic receptor subtype.
2000,
Pubmed
Capsoni,
Alzheimer-like neurodegeneration in aged antinerve growth factor transgenic mice.
2000,
Pubmed
Carbone,
Pentameric concatenated (alpha4)(2)(beta2)(3) and (alpha4)(3)(beta2)(2) nicotinic acetylcholine receptors: subunit arrangement determines functional expression.
2009,
Pubmed
,
Xenbase
Celie,
Crystal structure of nicotinic acetylcholine receptor homolog AChBP in complex with an alpha-conotoxin PnIA variant.
2005,
Pubmed
,
Xenbase
Conroy,
Nicotinic receptor subtypes in the developing chick brain: appearance of a species containing the alpha4, beta2, and alpha5 gene products.
1998,
Pubmed
Court,
Attenuation of Abeta deposition in the entorhinal cortex of normal elderly individuals associated with tobacco smoking.
2005,
Pubmed
Criado,
Expression and functional properties of α7 acetylcholine nicotinic receptors are modified in the presence of other receptor subunits.
2012,
Pubmed
,
Xenbase
Dajas-Bailador,
Nicotinic acetylcholine receptors and the regulation of neuronal signalling.
2004,
Pubmed
Dolga,
Pretreatment with lovastatin prevents N-methyl-D-aspartate-induced neurodegeneration in the magnocellular nucleus basalis and behavioral dysfunction.
2009,
Pubmed
Drisdel,
Neuronal alpha-bungarotoxin receptors are alpha7 subunit homomers.
2000,
Pubmed
Dumas,
The cholinergic hypothesis of cognitive aging revisited again: cholinergic functional compensation.
2011,
Pubmed
Eaton,
The unique α4+/-α4 agonist binding site in (α4)3(β2)2 subtype nicotinic acetylcholine receptors permits differential agonist desensitization pharmacology versus the (α4)2(β2)3 subtype.
2014,
Pubmed
,
Xenbase
Exley,
Presynaptic nicotinic receptors: a dynamic and diverse cholinergic filter of striatal dopamine neurotransmission.
2008,
Pubmed
Exley,
Alpha6-containing nicotinic acetylcholine receptors dominate the nicotine control of dopamine neurotransmission in nucleus accumbens.
2008,
Pubmed
Flora,
Neuronal and extraneuronal expression and regulation of the human alpha5 nicotinic receptor subunit gene.
2000,
Pubmed
Fraser,
Ionic effects of the Alzheimer's disease beta-amyloid precursor protein and its metabolic fragments.
1997,
Pubmed
George,
Function of human α3β4α5 nicotinic acetylcholine receptors is reduced by the α5(D398N) variant.
2012,
Pubmed
,
Xenbase
Girod,
Heteromeric complexes of alpha 5 and/or alpha 7 subunits. Effects of calcium and potential role in nicotine-induced presynaptic facilitation.
1999,
Pubmed
Gotti,
Selective nicotinic acetylcholine receptor subunit deficits identified in Alzheimer's disease, Parkinson's disease and dementia with Lewy bodies by immunoprecipitation.
2006,
Pubmed
Gotti,
Pharmacology and biophysical properties of alpha 7 and alpha 7-alpha 8 alpha-bungarotoxin receptor subtypes immunopurified from the chick optic lobe.
1994,
Pubmed
,
Xenbase
Gotti,
Expression of nigrostriatal alpha 6-containing nicotinic acetylcholine receptors is selectively reduced, but not eliminated, by beta 3 subunit gene deletion.
2005,
Pubmed
Gotti,
Neuronal nicotinic receptors: from structure to pathology.
2004,
Pubmed
Grady,
Rodent habenulo-interpeduncular pathway expresses a large variety of uncommon nAChR subtypes, but only the alpha3beta4* and alpha3beta3beta4* subtypes mediate acetylcholine release.
2009,
Pubmed
Griguoli,
Regulation of hippocampal inhibitory circuits by nicotinic acetylcholine receptors.
2012,
Pubmed
Halevi,
The C. elegans ric-3 gene is required for maturation of nicotinic acetylcholine receptors.
2002,
Pubmed
,
Xenbase
Hernandez,
Loss of alpha7 nicotinic receptors enhances beta-amyloid oligomer accumulation, exacerbating early-stage cognitive decline and septohippocampal pathology in a mouse model of Alzheimer's disease.
2010,
Pubmed
Holtzman,
Mouse model of neurodegeneration: atrophy of basal forebrain cholinergic neurons in trisomy 16 transplants.
1992,
Pubmed
Hurst,
Nicotinic acetylcholine receptors: from basic science to therapeutics.
2013,
Pubmed
Keyser,
Three subtypes of alpha-bungarotoxin-sensitive nicotinic acetylcholine receptors are expressed in chick retina.
1993,
Pubmed
Khiroug,
Rat nicotinic ACh receptor alpha7 and beta2 subunits co-assemble to form functional heteromeric nicotinic receptor channels.
2002,
Pubmed
,
Xenbase
Kozikowski,
Chemistry and pharmacology of nicotinic ligands based on 6-[5-(azetidin-2-ylmethoxy)pyridin-3-yl]hex-5-yn-1-ol (AMOP-H-OH) for possible use in depression.
2009,
Pubmed
Kuryatov,
Expression of functional human α6β2β3* acetylcholine receptors in Xenopus laevis oocytes achieved through subunit chimeras and concatamers.
2011,
Pubmed
,
Xenbase
Lendvai,
Nonsynaptic chemical transmission through nicotinic acetylcholine receptors.
2008,
Pubmed
Lewis,
High-affinity nicotinic acetylcholine receptor expression and trafficking abnormalities in psychiatric illness.
2013,
Pubmed
Liu,
A novel nicotinic mechanism underlies β-amyloid-induced neuronal hyperexcitation.
2013,
Pubmed
Liu,
Functional α7β2 nicotinic acetylcholine receptors expressed in hippocampal interneurons exhibit high sensitivity to pathological level of amyloid β peptides.
2012,
Pubmed
Liu,
A novel nicotinic acetylcholine receptor subtype in basal forebrain cholinergic neurons with high sensitivity to amyloid peptides.
2009,
Pubmed
,
Xenbase
Lukas,
International Union of Pharmacology. XX. Current status of the nomenclature for nicotinic acetylcholine receptors and their subunits.
1999,
Pubmed
Mazzaferro,
Additional acetylcholine (ACh) binding site at alpha4/alpha4 interface of (alpha4beta2)2alpha4 nicotinic receptor influences agonist sensitivity.
2011,
Pubmed
,
Xenbase
McCullumsmith,
Postmortem brain: an underutilized substrate for studying severe mental illness.
2014,
Pubmed
Murray,
α7β2 nicotinic acetylcholine receptors assemble, function, and are activated primarily via their α7-α7 interfaces.
2012,
Pubmed
,
Xenbase
Orr-Urtreger,
Mice deficient in the alpha7 neuronal nicotinic acetylcholine receptor lack alpha-bungarotoxin binding sites and hippocampal fast nicotinic currents.
1997,
Pubmed
Palma,
Nicotinic acetylcholine receptors assembled from the alpha7 and beta3 subunits.
1999,
Pubmed
,
Xenbase
Papke,
Tricks of perspective: insights and limitations to the study of macroscopic currents for the analysis of nAChR activation and desensitization.
2010,
Pubmed
,
Xenbase
Picciotto,
Abnormal avoidance learning in mice lacking functional high-affinity nicotine receptor in the brain.
1995,
Pubmed
Picciotto,
Acetylcholine as a neuromodulator: cholinergic signaling shapes nervous system function and behavior.
2012,
Pubmed
Pinto,
Revisiting the cholinergic hypothesis of behavioral and psychological symptoms in dementia of the Alzheimer's type.
2011,
Pubmed
Price,
The functional organization of the basal forebrain cholinergic system in primates and the role of this system in Alzheimer's disease.
1985,
Pubmed
Rayes,
Number and locations of agonist binding sites required to activate homomeric Cys-loop receptors.
2009,
Pubmed
Riganti,
Long-term exposure to the new nicotinic antagonist 1,2-bisN-cytisinylethane upregulates nicotinic receptor subtypes of SH-SY5Y human neuroblastoma cells.
2005,
Pubmed
Sala,
CC4, a dimer of cytisine, is a selective partial agonist at α4β2/α6β2 nAChR with improved selectivity for tobacco smoking cessation.
2013,
Pubmed
Schneider,
NIH Image to ImageJ: 25 years of image analysis.
2012,
Pubmed
Semba,
Multiple output pathways of the basal forebrain: organization, chemical heterogeneity, and roles in vigilance.
2000,
Pubmed
Stokes,
Use of an α3β4 nicotinic acetylcholine receptor subunit concatamer to characterize ganglionic receptor subtypes with specific subunit composition reveals species-specific pharmacologic properties.
2012,
Pubmed
,
Xenbase
Voytko,
Basal forebrain lesions in monkeys disrupt attention but not learning and memory.
1994,
Pubmed
Wenk,
A primate model of Alzheimer's disease.
1993,
Pubmed
Whiteaker,
Discovery, synthesis, and structure activity of a highly selective alpha7 nicotinic acetylcholine receptor antagonist.
2007,
Pubmed
,
Xenbase
Whiteaker,
125I-alpha-conotoxin MII identifies a novel nicotinic acetylcholine receptor population in mouse brain.
2000,
Pubmed
Williams,
The effective opening of nicotinic acetylcholine receptors with single agonist binding sites.
2011,
Pubmed
,
Xenbase
Xiao,
Sazetidine-A, a novel ligand that desensitizes alpha4beta2 nicotinic acetylcholine receptors without activating them.
2006,
Pubmed
Yakel,
Cholinergic receptors: functional role of nicotinic ACh receptors in brain circuits and disease.
2013,
Pubmed
Zhang,
Postnatal changes of nicotinic acetylcholine receptor alpha 2, alpha 3, alpha 4, alpha 7 and beta 2 subunits genes expression in rat brain.
1998,
Pubmed
Zhou,
Human alpha4beta2 acetylcholine receptors formed from linked subunits.
2003,
Pubmed
,
Xenbase
Zoli,
Developmental regulation of nicotinic ACh receptor subunit mRNAs in the rat central and peripheral nervous systems.
1995,
Pubmed
Zwart,
Unique pharmacology of heteromeric α7β2 nicotinic acetylcholine receptors expressed in Xenopus laevis oocytes.
2014,
Pubmed
,
Xenbase
