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α3

Family: Nicotinic acetylcholine receptors

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Tissue Distribution
Physiological Consequences of Altering Gene Expression
Clinically-Relevant Mutations and Pathophysiology
References
Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 505 15q24 CHRNA3 cholinergic receptor, nicotinic, alpha 3 (neuronal) 4
Mouse 4 504 9 B Chrna3 cholinergic receptor, nicotinic, alpha polypeptide 3 2
Rat 4 499 8q24 Chrna3 cholinergic receptor, nicotinic, alpha 3 (neuronal) 3
Previous and Unofficial Names
Autonomic, ganglionic
cholinergic receptor, nicotinic, alpha polypeptide 3
acetylcholine receptor, nicotinic, alpha 3 (neuronal)
cholinergic receptor, nicotinic, alpha polypeptide 4
cholinergic receptor nicotinic alpha polypeptide 4
cholinergic receptor, nicotinic, alpha 3
neuronal acetylcholine receptor subunit alpha-3
neuronal nicotinic acetylcholine receptor, alpha 3 subunit
alpha 3
(a)3
Acra-3
Acra3
A730007P14Rik
acetylcholine receptor alpha 3 (neuronal nicotine)
Database Links
ChEMBL Target 11184 (Hs), 10669 (Rn)
Ensembl ENSG00000080644 (Hs), ENSMUSG00000032303 (Mm), ENSRNOG00000013829 (Rn)
Entrez Gene 1136 (Hs), 110834 (Mm), 25101 (Rn)
GeneCards CHRNA3 (Hs)
GenitoUrinary Development Molecular Anatomy Project Chrna3 (Mm)
HomoloGene 591
Human Protein Reference Database 07511 (Hs)
InterPro P32297 (Hs), Q8R4G9 (Mm), P04757 (Rn)
KEGG Gene hsa:1136 (Hs), mmu:110834 (Mm), rno:25101 (Rn)
OMIM 118503 (Hs)
PharmGKB Gene PA113 (Hs)
PhosphoSitePlus P32297 (Hs), Q8R4G9 (Mm), P04757 (Rn)
Protein Ontology (PRO) PRO:000005456 (Hs)
RefSeq Nucleotide NM_000743 (Hs), NM_145129 (Mm), NM_052805 (Rn)
RefSeq Protein NP_000734 (Hs), NP_660111 (Mm), NP_434692 (Rn)
TreeFam ENSG00000080644 (Hs), ENSMUSG00000032303 (Mm), ENSRNOG00000013829 (Rn)
UniGene Hs. 89605 (Hs)
UniProt P32297 (Hs), Q8R4G9 (Mm), P04757 (Rn)
Wikipedia α3
Nicotinic acetylcholine receptors
Search for 3D structures on the PDB
Search by keyword: Nicotinic acetylcholine receptors α3 Search by accession number: P04757, P32297, Q8R4G9
Natural/Endogenous Ligand(s)
acetylcholine
Commonly used antagonists (Human)
α3β2: DHβE (KB = 1.6 μM, IC50 = 2.0 μM), (+)-tubocurarine (KB = 2.4 μM); α3β4: DHβE (KB = 19 μM, IC50 = 26 μM), (+)-tubocurarine (KB = 2.2 μM)
Tissue Distribution
Brain:-
High levels of α3-subunit mRNA are expressed in the medial habenula. Expression has also been detected in substantia nigra pars compacta and ventral tegmental area (similar patterns seen in rat)
Expression level:  High
Species:  Mouse
Technique:  in situ hybridisation
References:  5
Brain:-
Intense expression in the medial habenula with lower levels of expression in cortical layer IV, substantia nigra pars compacta, ventral tegmental area and in several hindbrain nuclei. Significant hybridization was also noted in the superficial layers of the superior colliculus and in inferior colliculus In contrast to rat brain, little hybridization was observed in thalamus.
Expression level:  High
Species:  Mouse
Technique:  in situ hybridisation
References:  9
Olfactory bulbs, including the mitral cell layer and the accessory olfactory bulb. Whiteaker et al. 2000
Species:  Mouse
Technique:  in situ hybridisation
References:  17
Brain:-
Deletion of the α3 nAChR subunit gene in knockout mice decreases the levels of A85380-resistant [125I]-epibatidine binding in the medial habenula–fasciculus retroflexus–interpenduncular nucleus tract, the dorsal cortex of the inferior colliculus, and the medial vestibular and prepositus hypoglossal nuclei.
Species:  Mouse
Technique:  Radioligand binding
References:  18
Brain:-
Intense expression in the medial habenula with less pronounced expression in the substantia nigra pars compacta and ventral tegmental area. In addition, hybridization was detected in olfactory bulb, cortical layer IV, basal lateral amygdala, interpeduncular nucleus, locus coeruleus, and several hindbrain nuclei, including motor nuclei such as motor nucleus V, facial nerve VII and nucleus ambiguous. Labeling was also observed in several thalamic areas.
Expression level:  High
Species:  Rat
Technique:  in situ hybridisation
References:  16
Sympathetic and parasympathetic nervous system
Species:  Rat
Technique:  RT-PCR and in situ hybridization.
References:  8,10-11
Tissue Distribution Comments
In situ hybridization of rhesus monkey (Macaca mulatta) brain shows that expression appears to be restricted primarily to the medial habenula with minor expression in the hippocampus [6].
Physiological Consequences of Altering Gene Expression
Heterozygous α3 mice are less sensitive to nicotine-induced seizures.
Species:  Mouse
Tissue:  in vivo
Technique:  Knockout
References:  14
Administration of α3 antisense RNA into cerebral ventricles for seven days reduced α3 mRNA levels in both thalamus and medial habenula. Hypothermia elicited by epibatidine administration was unaffected, but sensitivity to seizures elicited by epibatidine was significantly reduced.
Species:  Rat
Tissue:  Brain (cerebral ventricles)
Technique:  Antisense knockdown
References:  1
Knockout mice have extensive autonomic dysfunctions. Phenotypic effects include bladder enlargement, dribbling urination, bladder infection, urinary stones and dilated ocular pupils. Mice survive to birth but have impaired growth and increased perinatal mortality.
Species:  Mouse
Tissue:  in vivo
Technique:  Knockout (homologous recombination)
References:  19
Clinically-Relevant Mutations and Pathophysiology
Disease:  Sporadic amyotrophic lateral sclerosis
References:  12
Click column headers to sort
Type Species Molecular location Description Reference
Missense Human M3-M4 intracellular loop 12
Disease:  Nicotine dependence, lung cancer, peripheral arterial disease
References:  7,13,15
Click column headers to sort
Type Species Molecular location Description Reference
Variant Human common variant in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 15

REFERENCES

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1. Adams, MR; Nikkel, AL; Donnelly-Roberts, DL; Watt, AT; Johnston, JF; Cowsert, LM; Butler, M; Kroeger, PE; Frost, L; Curzon, P; et al.. (2004) In vitro and in vivo effects of an alpha3 neuronal nicotinic acetylcholine receptor antisense oligonucleotide. Brain Res. Mol. Brain Res., 129 (1-2): 67-79. [PMID:15469883]

2. Bessis, A; Simon-Chazottes, D; Devillers-Thiéry, A; Guénet, JL; Changeux, JP. (1990) Chromosomal localization of the mouse genes coding for alpha 2, alpha 3, alpha 4 and beta 2 subunits of neuronal nicotinic acetylcholine receptor. FEBS Lett., 264 (1): 48-52. [PMID:2338144]

3. Boulter, J; Evans, K; Goldman, D; Martin, G; Treco, D; Heinemann, S; Patrick, J. (1986) Isolation of a cDNA clone coding for a possible neural nicotinic acetylcholine receptor alpha-subunit. Nature, 319 (6052): 368-74. [PMID:3753746]

4. Fornasari, D; Chini, B; Tarroni, P; Clementi, F. (1990) Molecular cloning of human neuronal nicotinic receptor alpha 3-subunit. Neurosci. Lett., 111 (3): 351-6. [PMID:2336208]

5. Goldman, D; Simmons, D; Swanson, LW; Patrick, J; Heinemann, S. (1986) Mapping of brain areas expressing RNA homologous to two different acetylcholine receptor alpha-subunit cDNAs. Proc. Natl. Acad. Sci. U.S.A., 83 (11): 4076-80. [PMID:3012549]

6. Han, ZY; Le Novère, N; Zoli, M; Hill, JA; Champtiaux, N; Changeux, JP. (2000) Localization of nAChR subunit mRNAs in the brain of Macaca mulatta. Eur. J. Neurosci., 12 (10): 3664-74. [PMID:11029636]

7. Improgo, MR; Scofield, MD; Tapper, AR; Gardner, PD. (2010) The nicotinic acetylcholine receptor CHRNA5/A3/B4 gene cluster: dual role in nicotine addiction and lung cancer. Prog. Neurobiol., 92 (2): 212-26. [PMID:20685379]

8. Mandelzys, A; Pié, B; Deneris, ES; Cooper, E. (1994) The developmental increase in ACh current densities on rat sympathetic neurons correlates with changes in nicotinic ACh receptor alpha-subunit gene expression and occurs independent of innervation. J. Neurosci., 14 (4): 2357-64. [PMID:8158273]

9. Marks, MJ; Pauly, JR; Gross, SD; Deneris, ES; Hermans-Borgmeyer, I; Heinemann, SF; Collins, AC. (1992) Nicotine binding and nicotinic receptor subunit RNA after chronic nicotine treatment. J. Neurosci., 12 (7): 2765-84. [PMID:1613557]

10. Poth, K; Nutter, TJ; Cuevas, J; Parker, MJ; Adams, DJ; Luetje, CW. (1997) Heterogeneity of nicotinic receptor class and subunit mRNA expression among individual parasympathetic neurons from rat intracardiac ganglia. J. Neurosci., 17 (2): 586-96. [PMID:8987781]

11. Rust, G; Burgunder, JM; Lauterburg, TE; Cachelin, AB. (1994) Expression of neuronal nicotinic acetylcholine receptor subunit genes in the rat autonomic nervous system. Eur. J. Neurosci., 6 (3): 478-85. [PMID:8019684]

12. Sabatelli, M; Eusebi, F; Al-Chalabi, A; Conte, A; Madia, F; Luigetti, M; Mancuso, I; Limatola, C; Trettel, F; Sobrero, F; et al.. (2009) Rare missense variants of neuronal nicotinic acetylcholine receptor altering receptor function are associated with sporadic amyotrophic lateral sclerosis. Hum. Mol. Genet., 18 (20): 3997-4006. [PMID:19628475]

13. Saccone, SF; Hinrichs, AL; Saccone, NL; Chase, GA; Konvicka, K; Madden, PA; Breslau, N; Johnson, EO; Hatsukami, D; Pomerleau, O; et al.. (2007) Cholinergic nicotinic receptor genes implicated in a nicotine dependence association study targeting 348 candidate genes with 3713 SNPs. Hum. Mol. Genet., 16 (1): 36-49. [PMID:17135278]

14. Salas, R; Cook, KD; Bassetto, L; De Biasi, M. (2004) The alpha3 and beta4 nicotinic acetylcholine receptor subunits are necessary for nicotine-induced seizures and hypolocomotion in mice. Neuropharmacology, 47 (3): 401-7. [PMID:15275829]

15. Thorgeirsson, TE; Geller, F; Sulem, P; Rafnar, T; Wiste, A; Magnusson, KP; Manolescu, A; Thorleifsson, G; Stefansson, H; Ingason, A; et al.. (2008) A variant associated with nicotine dependence, lung cancer and peripheral arterial disease. Nature, 452 (7187): 638-42. [PMID:18385739]

16. Wada, E; Wada, K; Boulter, J; Deneris, E; Heinemann, S; Patrick, J; Swanson, LW. (1989) Distribution of alpha 2, alpha 3, alpha 4, and beta 2 neuronal nicotinic receptor subunit mRNAs in the central nervous system: a hybridization histochemical study in the rat. J. Comp. Neurol., 284 (2): 314-35. [PMID:2754038]

17. Whiteaker, P; Jimenez, M; McIntosh, JM; Collins, AC; Marks, MJ. (2000) Identification of a novel nicotinic binding site in mouse brain using [(125)I]-epibatidine. Br. J. Pharmacol., 131 (4): 729-39. [PMID:11030722]

18. Whiteaker, P; Peterson, CG; Xu, W; McIntosh, JM; Paylor, R; Beaudet, AL; Collins, AC; Marks, MJ. (2002) Involvement of the alpha3 subunit in central nicotinic binding populations. J. Neurosci., 22 (7): 2522-9. [PMID:11923417]

19. Xu, W; Gelber, S; Orr-Urtreger, A; Armstrong, D; Lewis, RA; Ou, CN; Patrick, J; Role, L; De Biasi, M; Beaudet, AL. (1999) Megacystis, mydriasis, and ion channel defect in mice lacking the alpha3 neuronal nicotinic acetylcholine receptor. Proc. Natl. Acad. Sci. U.S.A., 96 (10): 5746-51. [PMID:10318955]

To cite this database page, please use the following:

Cecilia Gotti, Michael. J. Marks, Neil S. Millar, Susan Wonnacott.
Nicotinic acetylcholine receptors: α3. Last modified on 11/10/2012. Accessed on 24/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=464.


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