Nomenclature: β3

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 4 458 8p11.2 CHRNB3 cholinergic receptor, nicotinic, beta 3 (neuronal) 11
Mouse 4 464 8 A3 Chrnb3 cholinergic receptor, nicotinic, beta polypeptide 3 4
Rat 4 464 16q12.3 Chrnb3 cholinergic receptor, nicotinic, beta 3 (neuronal) 3
Previous and Unofficial Names
cholinergic receptor, nicotinic, beta polypeptide 3
acetylcholine receptor, nicotinic, beta 3 (neuronal)
cholinergic receptor, nicotinic, beta 3
neuronal acetylcholine receptor subunit beta-3
Acrb3
5730417K16Rik
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Natural/Endogenous Ligands
acetylcholine
Tissue Distribution
Brain: substantia nigra pars compacta, ventral tegmental area, locus coeruleus, medial habenula, superior colliculus.
Expression level:  High
Species:  Mouse
Technique:  in situ hybridisation
References:  2
Brain: substantia nigra pars compacta, ventral tegmental area, locus coeruleus, medial habenula
Expression level:  High
Species:  Rat
Technique:  in situ hybridisation
References:  3
Tissue Distribution Comments
The pattern of expression of β3 mRNA in rat brain resemples that of α6 however, in contrast to α6, high levels of expression occur in the medial habenula [3]. In rhesus monkey (Macaca mulatta) brain the expression pattern is similar to that in rodents, with high levels of in substantia nigra pars compacta, vertral tegmental area and medial habenula [8]. As with patterns in squirrel monkey (Saimiri sciureus) brain (showing high levels of expression in substantia nigra pars compacta, vertral tegmental area and medial habenula) [9].

Comparison of radioligand binding in wild-type and β3 knockout mice reveals no significant difference in high affinity [3H]-nicotine binding but a decrease in cytisine-resistant [3H]-epibatidine binding and a substantial decrease in the density of [125I]α-conotoxinMII binding in the visual and mesostriatal pathways. However, the reduction in [125I] α-conotoxinMII binding in β3 knockout mice is less dramatic than in α6 knockout mice [1-2].

Radioligand binding and immunoprecipitation studies with β3 knockout mice also reveal a reduction in α6-containing receptors in the striatum, midbrain and superior colliculus, indicating that a substantial fraction of α6 receptors also contain theβ3 subunit. β3-containing receptors not associated with the α6 subunit are selectively expressed in the medial habenula [5-7].
Physiological Consequences of Altering Gene Expression
Knockout mice have altered locomotor activity and altered prepulse inhibition of acoustic startle. Mice survive to birth but have impaired growth and increased perinatal mortality.
Species:  Mouse
Tissue:  in vivo
Technique:  Gene knockout
References:  2
Clinically-Relevant Mutations and Pathophysiology
Disease:  Nicotine dependence and lung cancer
OMIM:  188890
References:  10
Mutations not determined
General Comments
The mouse β3 subunit exists as two variants, the largest of which is tabulated above.

REFERENCES

1. Baddick CG, Marks MJ. (2011) An auroradiographic survey of mouse brain nicotinic acetylcholine receptors defined by null mutants. Biochem. Pharmacol.,, . [PMID:21575611]

2. Cui C, Booker TK, Allen RS, Grady SR, Whiteaker P, Marks MJ, Salminen O, Tritto T, Butt CM, Allen WR et al.. (2003) The beta3 nicotinic receptor subunit: a component of alpha-conotoxin MII-binding nicotinic acetylcholine receptors that modulate dopamine release and related behaviors. J. Neurosci.23 (35): 11045-53. [PMID:14657161]

3. Deneris ES, Boulter J, Swanson LW, Patrick J, Heinemann S. (1989) Beta 3: a new member of nicotinic acetylcholine receptor gene family is expressed in brain. J. Biol. Chem.264 (11): 6268-72. [PMID:2703489]

4. Drescher DG, Khan KM, Green GE, Morley BJ, Beisel KW, Kaul H, Gordon D, Gupta AK, Drescher MJ, Barretto RL. (1995) Analysis of nicotinic acetylcholine receptor subunits in the cochlea of the mouse. Comp. Biochem. Physiol. C, Pharmacol. Toxicol. Endocrinol.112 (3): 267-73. [PMID:8838678]

5. Gotti C, Moretti M, Clementi F, Riganti L, McIntosh JM, Collins AC, Marks MJ, Whiteaker P. (2005) Expression of nigrostriatal alpha 6-containing nicotinic acetylcholine receptors is selectively reduced, but not eliminated, by beta 3 subunit gene deletion. Mol. Pharmacol.67 (6): 2007-15. [PMID:15749993]

6. Gotti C, Moretti M, Zanardi A, Gaimarri A, Champtiaux N, Changeux JP, Whiteaker P, Marks MJ, Clementi F, Zoli M. (2005) Heterogeneity and selective targeting of neuronal nicotinic acetylcholine receptor (nAChR) subtypes expressed on retinal afferents of the superior colliculus and lateral geniculate nucleus: identification of a new native nAChR subtype alpha3beta2(alpha5 or beta3) enriched in retinocollicular afferents. Mol. Pharmacol.68 (4): 1162-71. [PMID:16049166]

7. Grady SR, Moretti M, Zoli M, Marks MJ, Zanardi A, Pucci L, Clementi F, Gotti C. (2009) Rodent habenulo-interpeduncular pathway expresses a large variety of uncommon nAChR subtypes, but only the alpha3beta4* and alpha3beta3beta4* subtypes mediate acetylcholine release. J. Neurosci.29 (7): 2272-82. [PMID:19228980]

8. 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]

9. 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]

10. 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]

11. Willoughby JJ, Ninkina NN, Beech MM, Latchman DS, Wood JN. (1993) Molecular cloning of a human neuronal nicotinic acetylcholine receptor beta 3-like subunit. Neurosci. Lett.155 (2): 136-9. [PMID:7690916]

To cite this database page, please use the following:

Cecilia Gotti, Michael. J. Marks, Neil S. Millar, Susan Wonnacott.
Nicotinic acetylcholine receptors: β3. Last modified on 14/03/2014. Accessed on 02/09/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=473.

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