Biology:CHRNA6
 Generic protein structure example |
Cholinergic receptor, nicotinic, alpha 6, also known as nAChRα6, is a protein that in humans is encoded by the CHRNA6 gene.[1] The CHRNA6 gene codes for the α6 nicotinic receptor subunit that is found in certain types of nicotinic acetylcholine receptors found primarily in the brain.
Tissue distribution
α6-containing nicotinic acetylcholine receptors (nAChRs) show a restricted expression pattern in the brain. Neural nicotinic acetylcholine receptors containing α6 subunits are expressed on dopamine-releasing neurons in the midbrain.[2][3]
Function
These receptors play a key role in regulating dopaminergic neurotransmission. Dopamine release following activation of these neurons is thought to be involved in the addictive properties of nicotine.[4][5][6] In addition to nicotine, research in animals has implicated α6-containing nAChRs in the abusive and addictive properties of ethanol, with mecamylamine demonstrating a potent ability to block these properties.
Clinical significance
Because of their selective distribution and role in dopamine regulation, α6-containing receptors have been investigated as therapeutic targets. Due to their selective localisation on dopaminergic neurons, α6-containing nACh receptors have also been suggested as a possible therapeutic target for the treatment of Parkinson's disease.[7][8]
Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles.[§ 1]
- ↑ The interactive pathway map can be edited at WikiPathways: "NicotineDopaminergic_WP1602". http://www.wikipathways.org/index.php/Pathway:WP1602.
See also
References
- ↑ "Entrez Gene: CHRNA6 cholinergic receptor, nicotinic, alpha 6". https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=8973.
- ↑ "Neuronal nicotinic receptor alpha 6 subunit mRNA is selectively concentrated in catecholaminergic nuclei of the rat brain". The European Journal of Neuroscience 8 (11): 2428–2439. November 1996. doi:10.1111/j.1460-9568.1996.tb01206.x. PMID 8950106.
- ↑ "The neuronal nicotinic acetylcholine receptors alpha 4* and alpha 6* differentially modulate dopamine release in mouse striatal slices". Journal of Neurochemistry 105 (5): 1761–1769. June 2008. doi:10.1111/j.1471-4159.2008.05266.x. PMID 18248619.
- ↑ "ACh/dopamine crosstalk in motor control and reward: a crucial role for alpha 6-containing nicotinic receptors?". Neuron 60 (1): 4–7. October 2008. doi:10.1016/j.neuron.2008.09.031. PMID 18940582.
- ↑ "In vivo activation of midbrain dopamine neurons via sensitized, high-affinity alpha 6 nicotinic acetylcholine receptors". Neuron 60 (1): 123–136. October 2008. doi:10.1016/j.neuron.2008.09.009. PMID 18940593.
- ↑ "Alpha6-containing nicotinic acetylcholine receptors dominate the nicotine control of dopamine neurotransmission in nucleus accumbens". Neuropsychopharmacology 33 (9): 2158–2166. August 2008. doi:10.1038/sj.npp.1301617. PMID 18033235.
- ↑ "Striatal alpha6* nicotinic acetylcholine receptors: potential targets for Parkinson's disease therapy". The Journal of Pharmacology and Experimental Therapeutics 316 (2): 481–489. February 2006. doi:10.1124/jpet.105.094375. PMID 16210393.
- ↑ "Nigrostriatal damage preferentially decreases a subpopulation of alpha6beta2* nAChRs in mouse, monkey, and Parkinson's disease striatum". Molecular Pharmacology 72 (1): 52–61. July 2007. doi:10.1124/mol.107.035998. PMID 17409284.
Further reading
- "The neuronal nicotinic receptor subunit genes (CHRNA6 and CHRNB3) are associated with subjective responses to tobacco". Human Molecular Genetics 17 (5): 724–734. March 2008. doi:10.1093/hmg/ddm344. PMID 18055561.
- "No evidence for association between 19 cholinergic genes and bipolar disorder". American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 144B (6): 715–723. September 2007. doi:10.1002/ajmg.b.30417. PMID 17373692.
- "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell 127 (3): 635–648. November 2006. doi:10.1016/j.cell.2006.09.026. PMID 17081983.
- "Nicotinic cholinergic receptor expression in the human nasal mucosa". The Annals of Otology, Rhinology, and Laryngology 112 (1): 77–84. January 2003. doi:10.1177/000348940311200115. PMID 12537063.
- "Genomic organization and promoter analysis of the human nicotinic acetylcholine receptor alpha6 subunit (CHNRA6) gene: Alu and other elements direct transcriptional repression". Gene 298 (1): 101–108. September 2002. doi:10.1016/S0378-1119(02)00925-3. PMID 12406580.
- "Immunohistochemical localisation of nicotinic acetylcholine receptor subunits in human cerebellum". Neuroscience 113 (3): 493–507. 2002. doi:10.1016/S0306-4522(02)00223-3. PMID 12150770.
- "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". Journal of Molecular Neuroscience 7 (3): 217–228. 1997. doi:10.1007/BF02736842. PMID 8906617.
External links
- CHRNA6+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
- Human CHRNA6 genome location and CHRNA6 gene details page in the UCSC Genome Browser.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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