Vesicular acetylcholine transporter
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{{Short description|Protein-coding gene in the species Homo sapiens}}
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The Vesicular acetylcholine transporter (VAChT) is a neurotransmitter transporter which is responsible for loading acetylcholine (ACh) into secretory organelles in neurons making acetylcholine available for secretion.{{cite journal | vauthors = Erickson JD, Varoqui H | title = Molecular analysis of vesicular amine transporter function and targeting to secretory organelles | journal = FASEB Journal | volume = 14 | issue = 15 | pages = 2450–8 | date = Dec 2000 | pmid = 11099462 | doi = 10.1096/fj.00-0206rev | doi-access = free | s2cid = 15305436 }}{{cite journal | vauthors = Weihe E, Tao-Cheng JH, Schäfer MK, Erickson JD, Eiden LE | title = Visualization of the vesicular acetylcholine transporter in cholinergic nerve terminals and its targeting to a specific population of small synaptic vesicles | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 93 | issue = 8 | pages = 3547–52 | date = Apr 1996 | pmid = 8622973 | pmc = 39647 | doi = 10.1073/pnas.93.8.3547 | doi-access = free | bibcode = 1996PNAS...93.3547W }} It is encoded by Solute carrier family 18, member 3 (SLC18A3) gene, located within the first intron of the choline acetyltransferase gene. VAChT is able to transport ACh into vesicles by relying on an exchange between protons (H+) that were previously pumped into the vesicle diffusing out, thus acting as an antiporter. ACh molecules are then carried into the vesicle by the action of exiting protons.{{cite web|last=Waymire|first=Jack|title=Storage of ACh|url=http://neuroscience.uth.tmc.edu/s1/chapter11.html|publisher=University of Texas Medical Center}} Acetylcholine transport utilizes a proton gradient established by a vacuolar ATPase.
VAChT uptake inhibitors
= Radiolabeled compounds =
PET imaging of the VAChT may provide insights into early diagnosis of Alzheimer's disease.
- (−)-trans-2-Hydroxy-3-(4-(4-
[ 18F] fluorobenzoyl)piperidino)tetralin; racemate: Ki = 2.70 nM for VAChT, 191 nM for σ1, and 251 nM for σ2{{cite journal | vauthors = Tu Z, Efange SM, Xu J, Li S, Jones LA, Parsons SM, Mach RH | title = Synthesis and in vitro and in vivo evaluation of 18F-labeled positron emission tomography (PET) ligands for imaging the vesicular acetylcholine transporter | journal = Journal of Medicinal Chemistry | volume = 52 | issue = 5 | pages = 1358–69 | date = Mar 2009 | pmid = 19203271 | pmc = 2765529 | doi = 10.1021/jm8012344 }}
References
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Further reading
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- {{cite journal | vauthors = Matsuo A, Bellier JP, Nishimura M, Yasuhara O, Saito N, Kimura H | title = Nuclear choline acetyltransferase activates transcription of a high-affinity choline transporter | journal = The Journal of Biological Chemistry | volume = 286 | issue = 7 | pages = 5836–45 | date = Feb 2011 | pmid = 21163949 | pmc = 3037696 | doi = 10.1074/jbc.M110.147611 | doi-access = free }}
- {{cite journal | vauthors = Lau JK, Brown KC, Thornhill BA, Crabtree CM, Dom AM, Witte TR, Hardman WE, McNees CA, Stover CA, Carpenter AB, Luo H, Chen YC, Shiflett BS, Dasgupta P | title = Inhibition of cholinergic signaling causes apoptosis in human bronchioalveolar carcinoma | journal = Cancer Research | volume = 73 | issue = 4 | pages = 1328–39 | date = Feb 2013 | pmid = 23222296 | doi = 10.1158/0008-5472.CAN-12-3190 | url = https://works.bepress.com/jamie_lau/3/download/ | doi-access = free | pmc = 10461321 }}
- {{cite journal | vauthors = Varoqui H, Erickson JD | title = Active transport of acetylcholine by the human vesicular acetylcholine transporter | journal = The Journal of Biological Chemistry | volume = 271 | issue = 44 | pages = 27229–32 | date = Nov 1996 | pmid = 8910293 | doi = 10.1074/jbc.271.44.27229 | doi-access = free}}
- {{cite journal | vauthors = Harold D, Peirce T, Moskvina V, Myers A, Jones S, Hollingworth P, Moore P, Lovestone S, Powell J, Foy C, Archer N, Walter S, Edmonson A, McIlroy S, Craig D, Passmore PA, Goate A, Hardy J, O'Donovan M, Williams J, Liddell M, Owen MJ, Jones L | title = Sequence variation in the CHAT locus shows no association with late-onset Alzheimer's disease | journal = Human Genetics | volume = 113 | issue = 3 | pages = 258–67 | date = Aug 2003 | pmid = 12759818 | doi = 10.1007/s00439-003-0960-2 | s2cid = 24977017 }}
- {{cite journal | vauthors = Morgan AR, Turic D, Jehu L, Hamilton G, Hollingworth P, Moskvina V, Jones L, Lovestone S, Brayne C, Rubinsztein DC, Lawlor B, Gill M, O'Donovan MC, Owen MJ, Williams J | title = Association studies of 23 positional/functional candidate genes on chromosome 10 in late-onset Alzheimer's disease | journal = American Journal of Medical Genetics Part B | volume = 144B | issue = 6 | pages = 762–70 | date = Sep 2007 | pmid = 17373700 | doi = 10.1002/ajmg.b.30509 | s2cid = 26081707 }}
- {{cite journal | vauthors = Schütz B, Chen L, Schäfer MK, Weihe E, Eiden LE | title = Somatomotor neuron-specific expression of the human cholinergic gene locus in transgenic mice | journal = Neuroscience | volume = 96 | issue = 4 | pages = 707–22 | year = 2000 | pmid = 10727789 | doi = 10.1016/s0306-4522(99)00587-4 | s2cid = 44276305 }}
- {{cite journal | vauthors = Khare P, Mulakaluri A, Parsons SM | title = Search for the acetylcholine and vesamicol binding sites in vesicular acetylcholine transporter: the region around the lumenal end of the transport channel | journal = Journal of Neurochemistry | volume = 115 | issue = 4 | pages = 984–93 | date = Nov 2010 | pmid = 20831599 | pmc = 2962730 | doi = 10.1111/j.1471-4159.2010.06990.x }}
- {{cite journal | vauthors = Tayebati SK, El-Assouad D, Ricci A, Amenta F | title = Immunochemical and immunocytochemical characterization of cholinergic markers in human peripheral blood lymphocytes | journal = Journal of Neuroimmunology | volume = 132 | issue = 1–2 | pages = 147–55 | date = Nov 2002 | pmid = 12417445 | doi=10.1016/s0165-5728(02)00325-9| s2cid = 20921312 }}
- {{cite journal | vauthors = Chireux MA, Le Van Thai A, Weber MJ | title = Human choline acetyltransferase gene: localization of alternative first exons | journal = Journal of Neuroscience Research | volume = 40 | issue = 4 | pages = 427–38 | date = Mar 1995 | pmid = 7616604 | doi = 10.1002/jnr.490400402 | s2cid = 42856768 }}
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External links
- {{MeshName|Vesicular+Acetylcholine+Transporter}}
{{Membrane transport proteins}}
{{Neurotransmitter transporters}}
{{Acetylcholine metabolism and transport modulators}}
Category:Solute carrier family
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