nicotinic acetylcholine receptor α6 subunit | Nicotinic acetylcholine receptors | IUPHAR/BPS Guide to PHARMACOLOGY

nicotinic acetylcholine receptor α6 subunit

Target id: 467

Nomenclature: nicotinic acetylcholine receptor α6 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 α6 subunit in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 494 8p11.21 CHRNA6 cholinergic receptor nicotinic alpha 6 subunit 4
Mouse 4 494 8 A3 Chrna6 cholinergic receptor, nicotinic, alpha polypeptide 6 2
Rat 4 493 16q12.3 Chrna6 cholinergic receptor nicotinic alpha 6 subunit
Previous and Unofficial Names
neuronal acetylcholine receptor subunit alpha-6 | Acra6 | cholinergic receptor, nicotinic, alpha 6 (neuronal) | cholinergic receptor, nicotinic alpha 6 | cholinergic receptor
Database Links
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands
acetylcholine
Commonly used antagonists (Human)
α6/α3β2β3 chimera: DHβE (IC50 = 1.1 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
[3H]epibatidine Ggal Full agonist 10.5 pKd
pKd 10.5 (Kd 3.5x10-11 M) native α6β4*
Antagonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
α-conotoxin MII Hs Antagonist - -
α6β2*
[125I]α-conotoxin MII Hs Antagonist - -
α-conotoxin PIA Hs Antagonist - -
α6/α3β2β3 chimera
α-conotoxin MII [H9A, L15A] Hs Antagonist - -
α6β2β3
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 5.0 pIC50 - no
pIC50 5.0 (IC50 1.1x10-5 M) α6/α3β2β3 chimera
Not voltage dependent
hexamethonium Hs - no 4.0 pIC50 - no
pIC50 4.0 (IC50 9.1x10-5 M) α6/α3β2β3 chimera
Not voltage dependent
Tissue Distribution
Brain:-
Expression of α6 mRNA in mouse brain is very similar to that described in rat brain. with high levels in the substantia nigra, ventral tegmental area and locus coeruleus.
Expression level:  High
Species:  Mouse
Technique:  in situ hybridisation
References:  2
Brain:-
Comparison of wild-type and α6 knockout mice identify α6-containing nAChRs in the striatum and retinal terminal fields
Species:  Mouse
Technique:  Immunoprecipitation, radioligand binding
References:  1
Brain:-
Comparison of the binding profiles of [3H]-cytisine, [3H]-epibatidine, and [3H]-nicotine in wild-type and α6 knockout mice reveal that the binding of all three ligands in α6 Ko mice is decreased in the retina, superior colliculus and nucleus geniculate lateralis. Decrease in [3H]-epibatidine binding in ventral tegmental area and caudate-putamen nuclei was observed when binding was performed in presence of 50 nM cytisine to block the binding of [3H]-epibatidine to the widely expressed striatal α4β2 subtype. In α6 knockout mice, the high affinity binding of [125I] α-conotoxinMII is eliminated from the visual system (retina, superior colliculus and nucleus geniculate lateralis) and from the mesostriatal dopaminergic system, which includes substantia nigra-ventral tegmental area neurons and their projecting structures (nucleus accumbens and caudate putamen).
Species:  Mouse
Technique:  Radioligand binding.
References:  2
Brain:-
α6 mRNA is expressed in the substantia nigra and locus coeruleus ( little detectable expression in other brain structures).
Expression level:  High
Species:  Rat
Technique:  in situ hybridisation
References:  6
Tissue Distribution Comments
Using in situ hybridisation research reveals that in rhesus monkey (Macaca mulatta) and squirrel monkey (Saimiri sciureus) the α6 mRNA distribution in brain is similar to rodents:- high levels in substantia nigra, ventral tegmental area, locus coeruleu, medial habenula [5,7].
Physiological Consequences of Altering Gene Expression
Knockout mice do not display any gross neurological or behavioural deficits but lack α-conotoxin MII binding sites in the brain.
Species:  Mouse
Tissue:  in vivo
Technique:  knockout
References:  2
Transgenic mice expressing α6 containing an L9’S substitution in the second transmembrane domain display extremely high activity during their active cycle in the dark. Mice also display locomotor activation following injection of low nicotine doses. Neurons in the ventral tegmental area are very sensitive to activation by nicotine. Enhanced response is observed for dopaminergic neurons. Synaptosomal dopamine release in striatal or olfactory tubercle preparations stimulated by nicotine is altered.
Species:  Mouse
Tissue: 
Technique:  Transgenesis
References:  3

References

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1. Champtiaux N, Gotti C, Cordero-Erausquin M, David DJ, Przybylski C, Léna C, Clementi F, Moretti M, Rossi FM, Le Novère N et al.. (2003) Subunit composition of functional nicotinic receptors in dopaminergic neurons investigated with knock-out mice. J. Neurosci., 23 (21): 7820-9. [PMID:12944511]

2. Champtiaux N, Han ZY, Bessis A, Rossi FM, Zoli M, Marubio L, McIntosh JM, Changeux JP. (2002) Distribution and pharmacology of alpha 6-containing nicotinic acetylcholine receptors analyzed with mutant mice. J. Neurosci., 22 (4): 1208-17. [PMID:11850448]

3. Drenan RM, Grady SR, Whiteaker P, McClure-Begley T, McKinney S, Miwa JM, Bupp S, Heintz N, McIntosh JM, Bencherif M et al.. (2008) In vivo activation of midbrain dopamine neurons via sensitized, high-affinity alpha 6 nicotinic acetylcholine receptors. Neuron, 60 (1): 123-36. [PMID:18940593]

4. Elliott KJ, Ellis SB, Berckhan KJ, Urrutia A, Chavez-Noriega LE, Johnson EC, Veliçelebi G, Harpold MM. (1996) Comparative structure of human neuronal alpha 2-alpha 7 and beta 2-beta 4 nicotinic acetylcholine receptor subunits and functional expression of the alpha 2, alpha 3, alpha 4, alpha 7, beta 2, and beta 4 subunits. J. Mol. Neurosci., 7 (3): 217-28. [PMID:8906617]

5. 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]

6. Le Novère N, Zoli M, Changeux JP. (1996) Neuronal nicotinic receptor alpha 6 subunit mRNA is selectively concentrated in catecholaminergic nuclei of the rat brain. Eur. J. Neurosci., 8 (11): 2428-39. [PMID:8950106]

7. Quik M, Polonskaya Y, Gillespie A, Jakowec M, Lloyd GK, Langston JW. (2000) Localization of nicotinic receptor subunit mRNAs in monkey brain by in situ hybridization. J. Comp. Neurol., 425 (1): 58-69. [PMID:10940942]

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 α6 subunit. Last modified on 14/07/2015. Accessed on 14/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=467.