Nomenclature: α2

Family: Nicotinic acetylcholine receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates. 

Contents

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 529 8p21 CHRNA2 cholinergic receptor, nicotinic, alpha 2 (neuronal) 12
Mouse 4 512 14 D1 Chrna2 cholinergic receptor, nicotinic, alpha polypeptide 2 (neuronal) 2
Rat 4 511 15p12 Chrna2 cholinergic receptor, nicotinic, alpha 2 (neuronal) 10
Previous and Unofficial Names
cholinergic receptor, nicotinic, alpha polypeptide 2 (neuronal)
acetylcholine receptor, nicotinic, alpha 2 (neuronal)
ACHR
neuronal acetylcholine receptor subunit alpha-2
nicotinic acetylcholine receptor
Acra-2
Acra2
BC011490
Database Links
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
Orphanet Gene
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Functional Characteristics
α2β2: PCa/PNa ~ 1.5
Natural/Endogenous Ligands
acetylcholine
Commonly used antagonists (Human)
α2β2: DHβE (KB = 0.9 μM), tubocurarine (KB = 1.4 μM); α2β4: DHβE (KB = 3.6 μM), tubocurarine (KB = 4.2 μM)
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[125I]epibatidine Rn Full agonist 10.08 – 11.0 pKd
pKd 11.0 – 10.68 (Kd 1x10-11 – 2.1x10-11 M) α2β2
pKd 10.08 – 10.06 (Kd 8.4x10-11 – 8.7x10-11 M) α2β4
[125I]epibatidine Hs Full agonist 10.38 pKd
pKd 10.38 (Kd 4.2x10-11 M) α2β4
[3H]epibatidine Hs Full agonist 10.38 pKd
pKd 10.38 (Kd 4.2x10-11 M) α2β4
[3H]epibatidine Rn Full agonist 10.06 – 10.68 pKd
pKd 11.0 – 10.68 (Kd 1x10-11 – 2.1x10-11 M) α2β2
pKd 10.08 – 10.06 (Kd 8.4x10-11 – 8.7x10-11 M) α2β4
[3H]cytisine Hs Full agonist - -
View species-specific agonist tables
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Use-dependent Affinity Units Concentration range (M) Voltage-dependent (mV) Reference
mecamylamine Hs - no - - - no

Not voltage dependent
hexamethonium Hs - no - - - no

Not voltage dependent
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Voltage-dependent (mV) Reference
LY2087101 Hs Positive - - - no 3
[3]
Not voltage dependent
Tissue Distribution
Brain:-
High levels of α2 subunit mRNA are expressed in the interpeduncular nucleus. Expression has also been detected in the dorsal and ventral tegmental nuclei in the hindbrain.
Expression level:  High
Species:  Mouse
Technique:  in situ hybridisation
References:  5-6
Brain:-
Radio-ligand binding studies in knockout mice provides evidence for expression of α2-containing nAChRs in interpeduncular nucleus and olfactory bulbs.
Species:  Mouse
Technique:  radio-ligand binding
References:  11
Brain:-
High levels of α2 subunit mRNA are expressed in the interpeduncular nucleus. Expression has also been detected in some areas of the olfactory bulbs, hippocampal formation, amgydala and a few brainstem nuclei. Developmental changes in expression have been reported, with expression in the cortex and hippocampus reaching a peak at postnatal day 7.
Expression level:  High
Species:  Rat
Technique:  in situ hybridisation
References:  5,8-10
Tissue Distribution Comments
In situ hybridization of rhesus monkey tissue shows that α1 mRNA appears to be more widely expressed in primate brain than in rodent brain. And relatively intense hybridization was observed in several thalamic nuclei of the Macaca mulatta brain with a pattern closely resembling that seen for α4. Low levels of expression in the interpeduncular nucleus (the site of most intense expression in rodents) [4].
Physiological Consequences of Altering Gene Expression
Nicotinic receptor α2 subunit knockout mice have reduced nicotine-induced modulation of long-term potentiation in the hippocampal CA1 region.
Species:  Mouse
Tissue:  in vivo
Technique:  Knockout (homologous recombination)
References:  7
Clinically-Relevant Mutations and Pathophysiology
Disease:  Familial sleep-related focal epilepsy
OMIM:  603204
References:  1
Click column headers to sort
Type Species Molecular location Description Reference
Missense Human I279N mutation (located in the first transmembrane domain) 1
Disease:  Nocturnal frontal lobe epilepsy, type 4
OMIM:  610353
Orphanet:  98784
References: 
Mutations not determined

REFERENCES

1. Aridon P, Marini C, Di Resta C, Brilli E, De Fusco M, Politi F, Parrini E, Manfredi I, Pisano T, Pruna D et al.. (2006) Increased sensitivity of the neuronal nicotinic receptor alpha 2 subunit causes familial epilepsy with nocturnal wandering and ictal fear. Am. J. Hum. Genet.79 (2): 342-50. [PMID:16826524]

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. Broad LM, Zwart R, Pearson KH, Lee M, Wallace L, McPhie GI, Emkey R, Hollinshead SP, Dell CP, Baker SR et al.. (2006) Identification and pharmacological profile of a new class of selective nicotinic acetylcholine receptor potentiators. J. Pharmacol. Exp. Ther.318 (3): 1108-17. [PMID:16738207]

4. 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]

5. Ishii K, Wong JK, Sumikawa K. (2005) Comparison of alpha2 nicotinic acetylcholine receptor subunit mRNA expression in the central nervous system of rats and mice. J. Comp. Neurol.493 (2): 241-60. [PMID:16255031]

6. 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]

7. Nakauchi S, Brennan RJ, Boulter J, Sumikawa K. (2007) Nicotine gates long-term potentiation in the hippocampal CA1 region via the activation of alpha2* nicotinic ACh receptors. Eur. J. Neurosci.25 (9): 2666-81. [PMID:17466021]

8. Son JH, Winzer-Serhan UH. (2006) Postnatal expression of alpha2 nicotinic acetylcholine receptor subunit mRNA in developing cortex and hippocampus. J. Chem. Neuroanat.32 (2-4): 179-90. [PMID:17046198]

9. 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]

10. Wada K, Ballivet M, Boulter J, Connolly J, Wada E, Deneris ES, Swanson LW, Heinemann S, Patrick J. (1988) Functional expression of a new pharmacological subtype of brain nicotinic acetylcholine receptor. Science240 (4850): 330-4. [PMID:2832952]

11. Whiteaker P, Wilking JA, Brown RW, Brennan RJ, Collins AC, Lindstrom JM, Boulter J. (2009) Pharmacological and immunochemical characterization of alpha2* nicotinic acetylcholine receptors (nAChRs) in mouse brain. Acta Pharmacol. Sin.30 (6): 795-804. [PMID:19498420]

12. Wood S, Schertzer M, Yaremko ML. (1995) Identification of the human neuronal nicotinic cholinergic alpha 2 receptor locus, (CHRNA2), within an 8p21 mapped locus, by sequence homology with rat DNA. Somat. Cell Mol. Genet.21 (2): 147-50. [PMID:7570187]

To cite this database page, please use the following:

Cecilia Gotti, Michael. J. Marks, Neil S. Millar, Susan Wonnacott.
Nicotinic acetylcholine receptors: α2. Last modified on 14/03/2014. Accessed on 22/08/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=463.

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