Cholinergic receptor, nicotinic, alpha 6, also known as nAChRα6, is a protein that in humans is encoded by the CHRNA6gene.[5] 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. Neural nicotinic acetylcholine receptors containing α6 subunits are expressed on dopamine-releasing neurons in the midbrain,[6][7] and dopamine release following activation of these neurons is thought to be involved in the addictive properties of nicotine.[8][9][10] 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.[11][12] In addition to nicotine, research in animals has implicated alpha-6-containing nAChRs in the abusive and addictive properties of ethanol, with mecamylamine demonstrating a potent ability to block these properties.
Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles.[§ 1]
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|alt=Nicotine Activity on Dopaminergic Neurons edit]]
Nicotine Activity on Dopaminergic Neurons edit
^The interactive pathway map can be edited at WikiPathways: "NicotineDopaminergic_WP1602".
^*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): 2428–2439. doi:10.1111/j.1460-9568.1996.tb01206.x. PMID 8950106. S2CID 23102912.
^Meyer EL, Yoshikami D, McIntosh JM (2008). "The Neuronal Nicotinic Acetylcholine Receptors α4* and α6* Differentially Modulate Dopamine Release in Mouse Striatal Slices". Journal of Neurochemistry. 105 (5): 1761–1769. doi:10.1111/j.1471-4159.2008.05266.x. PMC 2527994. PMID 18248619.
^Calabresi P, Massimiliano D (Oct 2008). "ACh/Dopamine Crosstalk in Motor Control and Reward: A Crucial Role for α6-Containing Nicotinic Receptors?". Neuron. 60 (1): 4–7. doi:10.1016/j.neuron.2008.09.031. PMID 18940582. S2CID 10537163.
^Drenan RM, Grady SR, Whiteaker P, McClure-Begley T, McKinney S, Miwa JM, Bupp S, Heintz N, et al. (2008). "In vivo activation of midbrain dopamine neurons via sensitized, high-affinity alpha 6 nicotinic acetylcholine receptors". Neuron. 60 (1): 123–136. doi:10.1016/j.neuron.2008.09.009. PMC 2632732. PMID 18940593.
^Exley R, Clements MA, Hartung H, McIntosh JM, Cragg SJ (2008). "Alpha6-containing nicotinic acetylcholine receptors dominate the nicotine control of dopamine neurotransmission in nucleus accumbens". Neuropsychopharmacology. 33 (9): 2158–2166. doi:10.1038/sj.npp.1301617. PMID 18033235.
^Quik M, McIntosh JM (2006). "Striatal alpha6* nicotinic acetylcholine receptors: potential targets for Parkinson's disease therapy". The Journal of Pharmacology and Experimental Therapeutics. 316 (2): 481–489. doi:10.1124/jpet.105.094375. PMID 16210393. S2CID 20050682.
^Bordia T, Grady SR, McIntosh JM, Quik M (2007). "Nigrostriatal damage preferentially decreases a subpopulation of alpha6beta2* nAChRs in mouse, monkey, and Parkinson's disease striatum". Molecular Pharmacology. 72 (1): 52–61. doi:10.1124/mol.107.035998. PMID 17409284. S2CID 25281990.
Further reading
Zeiger JS, Haberstick BC, Schlaepfer I, et al. (2008). "The neuronal nicotinic receptor subunit genes (CHRNA6 and CHRNB3) are associated with subjective responses to tobacco". Hum. Mol. Genet. 17 (5): 724–734. doi:10.1093/hmg/ddm344. PMID 18055561.
Shi J, Hattori E, Zou H, et al. (2007). "No Evidence for Association between 19 Cholinergic Genes and Bipolar Disorder". Am. J. Med. Genet. B Neuropsychiatr. Genet. 144 (6): 715–723. doi:10.1002/ajmg.b.30417. PMC 2576477. PMID 17373692.
Olsen JV, Blagoev B, Gnad F, et al. (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–648. doi:10.1016/j.cell.2006.09.026. PMID 17081983. S2CID 7827573.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–2127. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
Keiger CJ, Case LD, Kendal-Reed M, et al. (2003). "Nicotinic cholinergic receptor expression in the human nasal mucosa". Ann. Otol. Rhinol. Laryngol. 112 (1): 77–84. doi:10.1177/000348940311200115. PMID 12537063. S2CID 24705718.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–16903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Ebihara M, Ohba H, Ohno SI, Yoshikawa T (2003). "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. doi:10.1016/S0378-1119(02)00925-3. PMID 12406580.
Graham A, Court JA, Martin-Ruiz CM, et al. (2002). "Immunohistochemical localisation of nicotinic acetylcholine receptor subunits in human cerebellum". Neuroscience. 113 (3): 493–507. doi:10.1016/S0306-4522(02)00223-3. PMID 12150770. S2CID 39839166.
Elliott KJ, Ellis SB, Berckhan KJ, et al. (1997). "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): 217–228. doi:10.1007/BF02736842. PMID 8906617. S2CID 45737923.
