nicotinic acetylcholine receptor α2 subunit | Nicotinic acetylcholine receptors | IUPHAR/BPS Guide to PHARMACOLOGY

nicotinic acetylcholine receptor α2 subunit

Target id: 463

Nomenclature: nicotinic acetylcholine receptor α2 subunit

Family: Nicotinic acetylcholine receptors

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

   GtoImmuPdb view: OFF :     Currently no data for nicotinic acetylcholine receptor α2 subunit in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 529 8p21 CHRNA2 cholinergic receptor nicotinic alpha 2 subunit 13
Mouse 4 512 14 D1 Chrna2 cholinergic receptor, nicotinic, alpha polypeptide 2 (neuronal) 2
Rat 4 511 15p12 Chrna2 cholinergic receptor nicotinic alpha 2 subunit 11
Previous and Unofficial Names
neuronal acetylcholine receptor subunit alpha-2 | Acra2 | cholinergic receptor, nicotinic, alpha 2 (neuronal) | cholinergic receptor, nicotinic alpha 2 | cholinergic receptor, nicotinic, alpha 2 | cholinergic receptor
Database Links
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
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)

Download all structure-activity data for this target as a CSV file

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 10.1 – 11.0 pKd
pKd 10.7 – 11.0 (Kd 2.1x10-11 – 1x10-11 M) α2β2
pKd 10.1 – 10.1 (Kd 8.7x10-11 – 8.4x10-11 M) α2β4
[3H]epibatidine Rn Full agonist 10.1 – 11.0 pKd
pKd 10.7 – 11.0 (Kd 2.1x10-11 – 1x10-11 M) α2β2
pKd 10.1 – 10.1 (Kd 8.7x10-11 – 8.4x10-11 M) α2β4
[125I]epibatidine Hs Full agonist 10.4 pKd
pKd 10.4 (Kd 4.2x10-11 M) α2β4
[3H]epibatidine Hs Full agonist 10.4 pKd
pKd 10.4 (Kd 4.2x10-11 M) α2β4
CP-601927 Hs Partial agonist 8.9 pKi 7
pKi 8.9 (Ki 1.2x10-9 M) [7]
Description: Measured against α2β4 nAchRs- species not identified.
[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
hexamethonium Hs - no - - - no

Not voltage dependent
mecamylamine 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:  Radioligand binding
References:  12
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:  5,9-11
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:  8
Clinically-Relevant Mutations and Pathophysiology
Disease:  Epilepsy, nocturnal frontal lobe 4, ENFL4
Synonyms: Autosomal dominant nocturnal frontal lobe epilepsy [Orphanet: ORPHA98784]
OMIM: 610353
Orphanet: ORPHA98784
References:  1
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human I279N The amino acid substitution is located in the first transmembrane domain 1

References

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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. Mineur YS, Einstein EB, Seymour PA, Coe JW, O'neill BT, Rollema H, Picciotto MR. (2011) α4β2 nicotinic acetylcholine receptor partial agonists with low intrinsic efficacy have antidepressant-like properties. Behav Pharmacol, 22 (4): 291-9. [PMID:21566524]

8. 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]

9. 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]

10. 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]

11. 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. Science, 240 (4850): 330-4. [PMID:2832952]

12. 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]

13. 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]

Contributors

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How to cite this page

Cecilia Gotti, Michael. J. Marks, Neil S. Millar, Susan Wonnacott.
Nicotinic acetylcholine receptors: nicotinic acetylcholine receptor α2 subunit. Last modified on 11/07/2018. Accessed on 13/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=463.