5-HT2A receptor 4574063 224268349 2008-07-08T02:12:12Z ProteinBoxBot 3991663 Replaced protein Box Template with PBB Template for easy viewing. {{Wrongtitle|title=5-HT<sub>2A</sub> receptor}} {{PBB|geneid=3356}} The mammalian '''5-HT<sub>2A</sub> receptor''' is a subtype of the 5-HT<sub>2</sub> receptor which belongs to the [[serotonin receptor]] family and is a [[GPCR|G protein coupled receptor]] (GPCR). This is the main excitatory receptor subtype among the [[GPCR]]s for [[serotonin]] (5-HT), although 5-HT<sub>2A</sub> may also have an inhibitory effect on certain areas such as the [[visual cortex]] and the [[orbitofrontal cortex]]. This receptor was given importance first as the target of [[psychedelic]] drugs like [[LSD]]. Later it came back to prominence because it was also found to be mediating, at least partly, the action of many [[antipsychotic]] drugs, especially the [[atypical antipsychotic|atypical]] ones. 5-HT<sub>2A</sub> also happens to be a necessary receptor for the spread of the human [[polyoma virus]] called [[JC virus]]. ==History== Serotonin receptors were split into two classes by Gaddum and Picarelli when it was discovered that some of the serotonin-induced changes in the gut could be blocked by [[morphine]], whilst the remainder of the response was inhibited by [[dibenzyline]] leading to the naming of M and D receptors respectively. 5-HT<sub>2A</sub> is thought to correspond to what was originally described as D subtype of 5-HT receptors by Gaddum and Picarelli <ref>Chapter 11, Goodman & Gilman's The Pharmacological Basis of Therapeutics, 11th Edition </ref>. In the pre-molecular-cloning era when [[radioligand]] binding and displacement was the only major tool, spiperone and LSD were shown to label two different serotonin receptors, and neither of them displaced morphine, leading to naming of the [[5-HT1 receptor|5-HT<sub>1</sub>]], [[5-HT2 receptor|5-HT<sub>2</sub>]] and [[5-HT3 receptor|5-HT<sub>3</sub>]] receptors, corresponding to high affinity sites from [[LSD]], [[spiperone]] and morphine respectively (?). Later it was shown that the 5-HT<sub>2</sub> was very close to 5-HT<sub>1C</sub> and thus were clubbed together, renaming the 5-HT<sub>2</sub> into 5-HT<sub>2A</sub>. Thus the 5-HT<sub>2</sub> receptor family is comprised of three separate molecular entities: the 5-HT<sub>2A</sub> (erstwhile 5-HT<sub>2</sub> or D), the 5-HT<sub>2B</sub> (erstwhile 5-HT<sub>2F</sub>) and the 5-HT<sub>2C</sub> (erstwhile 5-HT<sub>1C</sub>) receptors.<ref name=Hoyer_2002>{{cite journal |author=Hoyer D, Hannon J, Martin G |title=Molecular, pharmacological and functional diversity of 5-HT receptors |journal=Pharmacol Biochem Behav |volume=71 |issue=4 |pages=533–54 |year=2002 |pmid=11888546 |doi=10.1016/S0091-3057(01)00746-8}}</ref> ==Distribution== 5-HT<sub>2A</sub> is expressed widely throughout the [[central nervous system]] (CNS). It is expressed near most of the serotoninergic terminal rich areas, including [[neocortex]] (mainly [[prefrontal]], [[parietal cortex|parietal]], and [[somatosensory cortex]]) and [[olfactory tubercle]]. There are especially high concentrations of this receptor on the [[apical dendrite]]s of [[pyramidal cell]]s in [[layer V]] of the cortex that may modulate cognitive processes. The protein has also been found in the [[Golgi cell]]s of the [[granular layer]] in the rat [[cerebellum]],<ref>{{Cite journal | author = [[Frederik J. Geurts]], [[Erik De Schutter]] and [[Jean-Pierre Timmermans]] | title = Localization of 5-HT2A, 5-HT3, 5-HT5A and 5-HT7 receptor-like immunoreactivity in the rat cerebellum | journal = [[Journal of Chemical Neuroanatomy]] | volume = 24 | issue = 1 | month = June | year = 2002 | pages = 65&ndash;74 | doi = 10.1016/S0891-0618(02)00020-0 | url = http://www.tnb.ua.ac.be/publications/pub060/pub060.shtml }}</ref> as well as in the [[Purkinje cell]]s (also in the rat cerebellum).<ref>{{Cite journal | author = Maeshima T, Shutoh F, Hamada S, Senzaki K, Hamaguchi-Hamada K, Ito R, Okado N. | title = Serotonin2A receptor-like immunoreactivity in rat cerebellar Purkinje cells | journal = [[Neurosci. Lett.]] | year = 1998 | month = August | volume = 252 | issue = 1 | pages = 72&ndash;74 | pmid = 9756362 | doi = 10.1016/S0304-3940(98)00546-1 }}</ref><ref>{{Cite journal | author = Maeshima T, Shiga T, Ito R, Okado N. | title = Expression of serotonin2A receptors in Purkinje cells of the developing rat cerebellum | journal = [[Neurosci. Res.]] | year = 2004 | month = December | volume = 50 | issue = 4 | pages = 411&ndash;417 | pmid = 15567478 | doi = 10.1016/j.neures.2004.08.010 }}</ref> In the periphery, it is highly expressed in [[platelets]] and many cell types of the [[cardiovascular]]system, as well as in [[fibroblast]]s, and within neurons of the peripheral nervous system. ==Signalling Cascade== The 5-HT<sub>2A</sub> receptor is known primarily to couple to the Galphaq signal transduction pathway. Upon receptor stimulation with agonist, Gaphaq and beta-gamma subunits dissociate to initiate downstream effector pathways. Galphaq stimulates [[phospholipase C]] (PLC) activity, which subsequently promotes the release of [[diglyceride|diacylglycerol]]&nbsp;(DAG) and [[inositol triphosphate]]&nbsp;(IP3), which in turn stimulate [[protein kinase C]]&nbsp;(PKC) activity and [[Ca2+|Ca<sup>2+</sup>]] release.<ref name="pmid16803859">{{cite journal | author = Urban JD, Clarke WP, von Zastrow M, Nichols DE, Kobilka B, Weinstein H, Javitch JA, Roth BL, Christopoulos A, Sexton PM, Miller KJ, Spedding M, Mailman RB | title = Functional selectivity and classical concepts of quantitative pharmacology | journal = J. Pharmacol. Exp. Ther. | volume = 320 | issue = 1 | pages = 1–13 | year = 2007 | pmid = 16803859 | doi = 10.1124/jpet.106.104463 | issn = }}</ref> There are many additional signal cascade components that include the formation of [[arachidonic acid]] through [[PLA2]] activity, activation of [[PLD]], [[Rho/RhoK]], and [[ERK]] pathway activation initiated by agonist stimulation of the receptor.{{Fact|date=November 2007}} ==Effects== Effects of activation of the receptor include: *CNS: neuronal excitation, behavioural effects, learning, anxiety *smooth muscle: contraction (in [[gastrointestinal tract]] & [[bronchi]])<ref name=Rang187/> *[[vasoconstriction]] / [[vasodilatation]] *platelets: aggregation ==Ligands== === Functional selectivity === 5-HT<sub>2A</sub>-receptor [[Ligand (biochemistry)|ligands]] may differentially activate the [[signal transduction|transductional pathways]] ([[#Signalling Cascade|see above]]). Studies evaluated the activation of two [[Effector (biology)|effectors]], [[Phospholipase C|PLC]] and [[Phospholipase A2|PLA2]], by means of their [[second messenger]]s. Compounds displaying more pronounced [[functional selectivity]] are [[Dimethoxyamphetamine#2,5-DMA|2,5-DMA]] and [[2C-N]]. The former induces [[Inositol triphosphate|IP]] accumulation without activating the PLA2 mediated response, while the latter elicits [[Arachidonic acid|AA]] release without activating the PLC mediated response.<!--other pathways were not examined in the reference--><ref name="pmid17337633">{{cite journal | author = Moya PR, Berg KA, Gutiérrez-Hernandez MA, Sáez-Briones P, Reyes-Parada M, Cassels BK, Clarke WP | title = Functional selectivity of hallucinogenic phenethylamine and phenylisopropylamine derivatives at human 5-hydroxytryptamine (5-HT)2A and 5-HT2C receptors | journal = J. Pharmacol. Exp. Ther. | volume = 321 | issue = 3 | pages = 1054–61 | year = 2007 | pmid = 17337633 | doi = 10.1124/jpet.106.117507 | issn = }}</ref><br/> [[Image:2,5-dma.png|80px]][[Image:2C-N.png|95px]] Recent research has suggested potential signaling differences within the somatosensory cortex between 5-HT<sub>2A</sub> agonists that produce [[headshake response|headshakes]] in the [[mouse]] and those that do not.<ref name="pmid17270739">{{cite journal | author = González-Maeso J, Weisstaub NV, Zhou M, Chan P, Ivic L, Ang R, Lira A, Bradley-Moore M, Ge Y, Zhou Q, Sealfon SC, Gingrich JA | title = Hallucinogens recruit specific cortical 5-HT(2A) receptor-mediated signaling pathways to affect behavior | journal = Neuron | volume = 53 | issue = 3 | pages = 439–52 | year = 2007 | pmid = 17270739 | doi = 10.1016/j.neuron.2007.01.008 | issn = }}</ref> The difference in signal transduction between the two 5-HT<sub>2A</sub> agonists serotonin and [[2,5-dimethoxy-4-iodoamphetamine|DOI]] may be due to the presence of the intracellular proteins called β-[[arrestin]]s, more specifically [[arrestin beta 2]].<ref name="pmid18195357">{{cite journal | author = Schmid CL, Raehal KM, Bohn LM | title = Agonist-directed signaling of the serotonin 2A receptor depends on beta-arrestin-2 interactions in vivo | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 105 | issue = 3 | pages = 1079–84 | year = 2008 | pmid = 18195357 | doi = 10.1073/pnas.0708862105 | issn = }}</ref><ref name="pmid18195368">{{cite journal | author = Abbas A, Roth BL | title = Arresting serotonin | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 105 | issue = 3 | pages = 831–2 | year = 2008 | pmid = 18195368 | doi = 10.1073/pnas.0711335105 | issn = }}</ref> ===Role of lipophilicity=== A set of ligands were evaluated. For "agonists", a highly significant linear correlation was observed between [[Dissociation constant#Protein-Ligand binding|binding affinity]] and [[lipophilicity]]. For ligands exhibiting partial agonist or antagonist properties, the lipophilicity was consistently higher than would be expected for an agonist of comparable affinity.<ref name="pmid18296055">{{cite journal | author = Parker MA, Kurrasch DM, Nichols DE | title = The role of lipophilicity in determining binding affinity and functional activity for 5-HT(2A) receptor ligands | journal = Bioorg. Med. Chem. | volume = | issue = | pages = | year = 2008 | pmid = 18296055 | doi = 10.1016/j.bmc.2008.02.033 | issn = }}</ref> ==="Agonists"=== Activation of the 5-HT<sub>2A</sub> [[receptor (biochemistry)|receptor]] is necessary for the effects of the "classic" [[hallucinogen]]s like [[LSD]], [[psilocin]] and [[mescaline]], which act as full or partial [[agonists]] at this receptor. Agonists acting at 5-HT<sub>2A</sub> receptors located on the apical dendrites of pyramidal cells within regions of the prefrontal cortex are believed to mediate hallucinogenic activity. ;Full agonists [[25I-NBOH|N-(2-hydroxybenzyl)-2C-I]] and [[25I-NBOMe|its 2-methoxy-analog]] are highly potent agonists at the human 5-HT<sub>2A</sub> receptor,<ref name="pmid17000863">{{cite journal | author = Braden MR, Parrish JC, Naylor JC, Nichols DE | title = Molecular interaction of serotonin 5-HT2A receptor residues Phe339(6.51) and Phe340(6.52) with superpotent N-benzyl phenethylamine agonists | journal = Mol. Pharmacol. | volume = 70 | issue = 6 | pages = 1956–64 | year = 2006 | pmid = 17000863 | doi = 10.1124/mol.106.028720 | issn = }}</ref> as are the benzocyclobutene derivative [[TCB-2]]<ref>McLean TH, Parrish JC, Braden MR, Marona-Lewicka D, Gallardo-Godoy A, Nichols DE. 1-Aminomethylbenzocycloalkanes: conformationally restricted hallucinogenic phenethylamine analogues as functionally selective 5-HT2A receptor agonists. ''Journal of Medicinal Chemistry''. 2006 Sep 21;49(19):5794-803. PMID 16970404</ref> and the benzodifuran derivative [[Br-DFLY]].<ref>Chambers JJ, Kurrasch-Orbaugh DM, Parker MA, Nichols DE. Enantiospecific synthesis and pharmacological evaluation of a series of super-potent, conformationally restricted 5-HT(2A/2C) receptor agonists. ''Journal of Medicinal Chemistry''. 2001 Mar 15;44(6):1003-10. PMID 11300881</ref> ;Partial agonists [[Methysergide]], a congener of [[methylergonovine]], used in treatment of [[migraine]] blocks 5-HT<sub>2A</sub> and 5-HT<sub>2C</sub> receptors, but sometimes acts as partial agonist, in some preparations. ==="Silent antagonists"=== Although [[ergot]] alkaloids are mostly nonspecific 5-HT receptor antagonists, a few ergot derivatives such as [[metergoline]] bind preferentially to members of the 5-HT<sub>2</sub> receptor family. A number of antagonists for 5-HT<sub>2A/2C</sub> are currently available but none are absolutely specific for 2A.{{Fact|date=April 2008}} [[Ketanserin]], the prototypic 5-HT<sub>2A</sub> receptor antagonist potently blocks 5-HT<sub>2A</sub> receptors, less potently blocks 5-HT<sub>2C</sub> receptors, and has no significant effect on 5-HT<sub>3</sub> or 5-HT<sub>4</sub> receptors or any members of the 5-HT<sub>1</sub> receptor family. Thus discovery of Ketanserin was a landmark in the pharmacology of 5-HT<sub>2</sub> receptors. Ketanserin, though capable of blocking 5-HT induced platelet adhesion, however does not mediate its well known antihypertensive action through 5-HT<sub>2</sub> receptor family, but through its high affinity for alpha adrenergic receptors. It also has high affinity for H<sub>1</sub> histaminergic receptors. Compounds chemically related to ketanserin such as ritanserin are more selective 5-HT<sub>2A</sub> receptor antagonists with low affinity for alpha-adrenergic receptors. However, ritanserin, like most other 5-HT<sub>2A</sub> receptor antagonists, also potently inhibit 5-HT<sub>2C</sub> receptors. Nefazadone operates by blocking post-synaptic serotonin type-2A receptors and to a lesser extent by inhibiting pre-synaptic serotonin and norepinephrine (noradrenaline) reuptake. [[Atypical antipsychotic]] drugs like [[Clozapine]], [[Olanzapine]], [[Quetiapine]], [[risperidone]] are relatively potent antagonists of 5-HT<sub>2A</sub> as are some of the lower potency old generation/typical antipsychotics. Other antagonists are [[Elsevier MDL|MDL]]-100907 (prototype of another new series of 5-HT<sub>2A</sub> antagonists) and [[Cyproheptadine]]. [[APD125]], a new sleeping pill recently developed by [[Arena Pharmaceuticals]] and currently in Phase 2 trials, acts as a selective 5-HT<sub>2A</sub> antagonist. [[Pizotifen]] is a non-selective antagonist.<ref name=Rang187> {{cite book |author=Rang, H. P. |title=Pharmacology |publisher=Churchill Livingstone |location=Edinburgh |year=2003 |pages= |isbn=0-443-07145-4 |oclc= |doi=}} Page 187 </ref> 2-alkyl-4-aryl-tetrahydro-pyrimido-azepines are subtype selective antagonists (35g: 60-fold).<ref>{{Cite journal | author = Brock T. Shireman, C. A. Dvorak, D. A. Rudolph, P. Bonaventure, D. Nepomuceno, L. Dvorak, K. L. Miller, T. W. Lovenberg, N. I. Carruthers NI | title = 2-Alkyl-4-aryl-pyrimidine fused heterocycles as selective 5-HT<sub>2A</sub> antagonists | journal = [[Bioorg. Med. Chem. Lett.]] | year = 2008 | month = March | volume = 18 | issue = 6 | pages = 2103–2108 | pmid = 18282705 | doi = 10.1016/j.bmcl.2008.01.090 }} </ref> == Genetics == [[Image:Chromosome 13.jpeg|thumb|right|[[Chromosome 13|Chromosome&nbsp;13]].]] The 5-HT<sub>2A</sub> receptors is coded by the HTR2A gene. In humans the gene is located on [[chromosome 13]]. The gene has previously been called just HTR2 until the description of two related genes [[HTR2B]] and [[HTR2C]]. Several interesting [[polymorphism (biology)|polymorphism]]s have been identified for HTR2A: -1438G/A ([[rs6311]]), T102C ([[rs6313]]) and His452Tyr ([[rs6314]]). === Associations with psychiatric disorders === Several studies have seen links between the -1438G/A polymorphism and [[mood disorders]], such as [[bipolar disorder]]<ref name="pmid11702051">{{Cite journal | author = Chee IS, Lee SW, Kim JL, Wang SK, Shin YO, Shin SC, Lee YH, Hwang HM, Lim MR | title = 5-HT2A receptor gene promoter polymorphism -1438A/G and bipolar disorder | journal = [[Psychiatr. Genet.]] | volume = 11 | issue = 3 | pages = 111–114 | year = 2001 | pmid = 11702051 | doi = | url = http://www.psychgenetics.com/pt/re/psychgen/abstract.00041444-200109000-00001.htm }}</ref> and [[major depressive disorder]].<ref name="pmid14730199">{{cite journal | author = Choi MJ, Lee HJ, Lee HJ, Ham BJ, Cha JH, Ryu SH, Lee MS | title = Association between major depressive disorder and the -1438A/G polymorphism of the serotonin 2A receptor gene | journal = [[Neuropsychobiology]] | volume = 49 | issue = 1 | pages = 38–41 | year = 2004 | pmid = 14730199 | doi = 10.1159/000075337 }}</ref> A weak link with an [[odds ratio]] of 1.3 has been found between the T102C polymorphism and [[schizophrenia]].<ref name="pmid8622505">{{cite journal | author = Williams J, Spurlock G, McGuffin P, Mallet J, Nöthen MM, Gill M, Aschauer H, Nylander PO, Macciardi F, Owen MJ | title = Association between schizophrenia and T102C polymorphism of the 5-hydroxytryptamine type 2a-receptor gene. European Multicentre Association Study of Schizophrenia (EMASS) Group | journal = [[The Lancet]] | volume = 347 | issue = 9011 | pages = 1294–1296 | year = 1996 | pmid = 8622505 }}</ref> This polymorphism has also been studies in relation to [[suicide]] attempts, with a study finding excess of the C/C genotypes among the suicide attempters.<ref>{{Cite journal | author = Vaquero-Lorenzo C, Baca-Garcia E, Diaz-Hernandez M, Perez-Rodriguez MM, Fernandez-Navarro P, Giner L, Carballo JJ, Saiz-Ruiz J, Fernandez-Piqueras J, Baldomero EB, de Leon J, Oquendo MA | title = Association study of two polymorphisms of the serotonin-2A receptor gene and suicide attempts | journal = [[Am J Med Genet B Neuropsychiatr Genet]] | doi = 10.1002/ajmg.b.30642 }} Electronic publication: 2007 December 28</ref> One study has found that genetic variations between individuals in the HTR2A gene may to some extent account for the difference in outcome of antidepressant treatment, so that patients suffering from [[major depressive disorder]] and treated with [[Citalopram]] may benefit more than others if they have one particular genotype.<ref name="pmid16642436">{{cite journal | author = McMahon FJ, Buervenich S, Charney D, Lipsky R, Rush AJ, Wilson AF, Sorant AJ, Papanicolaou GJ, Laje G, Fava M, Trivedi MH, Wisniewski SR, Manji H | title = Variation in the gene encoding the serotonin 2A receptor is associated with outcome of antidepressant treatment | journal = [[Am. J. Hum. Genet.]] | volume = 78 | issue = 5 | pages = 804–814 | year = 2006 | pmid = 16642436 | doi = 10.1086/503820 }}</ref> In this study 768 [[single nucleotide polymorphism]] (SNP) across 68 genes were investigated and a SNP&mdash;termed [[rs7997012]]&mdash;in the second [[intron]] of the HTR2A gene showed significant association with treatment outcome. Genetics seems also to be associated to some extent with the amount of adverse events in treatment of major depression disorder.<ref name="pmid17898344">{{cite journal | author = Laje G, Paddock S, Manji H, Rush AJ, Wilson AF, Charney D, McMahon FJ | title = Genetic markers of suicidal ideation emerging during citalopram treatment of major depression | journal = [[Am J Psychiatry]] | volume = 164 | issue = 10 | pages = 1530–1538 | year = 2007 | pmid = 17898344 | doi = 10.1176/appi.ajp.2007.06122018 }}</ref><ref name="pmid17949692">{{cite journal | author = Laje G, McMahon FJ | title = The pharmacogenetics of major depression: past, present, and future | journal = [[Biol. Psychiatry]] | volume = 62 | issue = 11 | pages = 1205–1207 | year = 2007 | pmid = 17949692 | doi = 10.1016/j.biopsych.2007.09.016 }}</ref> == Neuroimaging == The 5-HT<sub>2A</sub> receptors may be imaged with [[PET-scanner]]s using the fluorine-18-[[altanserin]]<ref name="pmid1744713">{{Cite journal | author = Lemaire C, Cantineau R, Guillaume M, Plenevaux A, Christiaens L | title = Fluorine-18-altanserin: a radioligand for the study of serotonin receptors with PET: radiolabeling and in vivo biologic behavior in rats | journal = [[Journal of Nuclear Medicine]] | volume = 32 | issue = 12 | pages = 2266–2272 | year = 1991 | pmid = 1744713 | url = http://jnm.snmjournals.org/cgi/content/abstract/32/12/2266 }}</ref> and MDL&nbsp;100,907<ref name="pmid8602111">{{Cite journal | author = Lundkvist C, Halldin C, Ginovart N, Nyberg S, Swahn CG, Carr AA, Brunner F, [[Lars Farde]] | title = <sup>11</sup>C-MDL 100907, a radioligland for selective imaging of 5-HT<sub>2A</sub> receptors with positron emission tomography | journal = [[Life Sci.]] | volume = 58 | issue = 10 | pages = PL 187–192 | year = 1996 | pmid = 8602111 | doi = 10.1016/0024-3205(96)00013-6 }}</ref> [[radioligand]]s that binds to the neuroreceptor, e.g., one study reported a ''reduced'' binding of altanserin particularly in the [[hippocampus]] in patients with [[major depressive disorder]].<ref name="pmid14744461">{{cite journal | author = Mintun MA, Sheline YI, Moerlein SM, Vlassenko AG, Huang Y, Snyder AZ | title = Decreased hippocampal 5-HT2A receptor binding in major depressive disorder: in vivo measurement with [18F]altanserin positron emission tomography | journal = [[Biological Psychiatry]] | volume = 55 | issue = 3 | pages = 217–24 | year = 2004 | pmid = 14744461 | doi = 10.1016/j.biopsych.2003.08.015}}</ref> Another PET study reported ''increased'' altanserin binding in the [[caudate nucleus|caudate nuclei]] in [[obsessive compulsive disorder]] patients compared to a healthy control group.<ref name="pmid15801987">{{Cite journal | author = Adams KH, Hansen ES, Pinborg LH, Hasselbalch SG, Svarer C, Holm S, Bolwig TG, Knudsen GM | title = Patients with obsessive-compulsive disorder have increased 5-HT2A receptor binding in the caudate nuclei | journal = [[International Journal of Neuropsychopharmacology]] | volume = 8 | issue = 3 | pages = 391–401 | year = 2005 | pmid = 15801987 | doi = 10.1017/S1461145705005055 }}</ref> Patients with [[Tourette's syndrome]] have also been scanned and the study found an increased binding of altanserin for patients compared to healthy controls.<ref name="pmid16945163">{{cite journal | author = Haugbøl S, Pinborg LH, Regeur L, Hansen ES, Bolwig TG, Nielsen FA, Svarer C, Skovgaard LT, Knudsen GM | title = Cerebral 5-HT2A receptor binding is increased in patients with Tourette's syndrome | journal = Int. J. Neuropsychopharmacol. | volume = 10 | issue = 2 | pages = 245–52 | year = 2007 | pmid = 16945163 | doi = 10.1017/S1461145706006559 | issn = }}</ref> The altanserin uptake decreases with [[aging|age]] reflecting a loss of specific 5-HT<sub>2A</sub> receptors with age.<ref name="pmid9027929">{{cite journal | author = Rosier A, Dupont P, Peuskens J, Bormans G, Vandenberghe R, Maes M, de Groot T, Schiepers C, Verbruggen A, Mortelmans L | title = Visualisation of loss of 5-HT<sub>2A</sub> receptors with age in healthy volunteers using [18F]altanserin and positron emission tomographic imaging | journal = [[Psychiatry Res.]] | volume = 68 | issue = 1 | pages = 11–22 | year = 1996 | pmid = 9027929 | doi = 10.1016/S0925-4927(96)02806-5 }}</ref><ref name="pmid9824691">{{Cite journal | author = Meltzer CC, Smith G, Price JC, Reynolds CF, Mathis CA, Greer P, Lopresti B, Mintun MA, Pollock BG, Ben-Eliezer D, Cantwell MN, Kaye W, DeKosky ST | title = Reduced binding of [18F]altanserin to serotonin type 2A receptors in aging: persistence of effect after partial volume correction | journal = [[Brain Res.]] | volume = 813 | issue = 1 | pages = 167–171 | year = 1998 | pmid = 9824691 | doi = 10.1016/S0006-8993(98)00909-3 }}</ref><ref name="pmid15006678">{{Cite journal | author = Adams KH, Pinborg LH, Svarer C, Hasselbalch SG, Holm S, Haugbøl S, Madsen K, Frøkjaer V, Martiny L, [[Olaf B. Paulson]], Knudsen GM | title = A database of [<sup>18</sup>F]-altanserin binding to 5-HT<sub>2A</sub> receptors in normal volunteers: normative data and relationship to physiological and demographic variables | journal = [[NeuroImage]] | volume = 21 | issue = 3 | pages = 1105–1113 | year = 2004 | pmid = 15006678 | doi = 10.1016/j.neuroimage.2003.10.046 }}</ref> A study has also found a positive correlation among healthy subjects between altanserin binding and the personality trait [[neuroticism]] as measure by the [[NEO PI-R]] personality questionnaire.<ref name="pmid17884017">{{Cite journal | author = Frøkjær VG, Mortensen EL, Nielsen FÅ, Haugbøl S, Pinborg LH, Adams KH, Svarer C, Hasselbalch SG, Holm S, [[Olaf B. Paulson]], Knudsen GM | title = Frontolimbic serotonin 2A receptor binding in healthy subjects is associated with personality risk factors for affective disorder | journal = [[Biological Psychiatry]] | volume = 63 | issue = 6 | pages = 569–76 | year = 2008 | pmid = 17884017 | doi = 10.1016/j.biopsych.2007.07.009 }}</ref> ==In virus endocytosis== 5-HT<sub>2A</sub> is a necessary receptor for [[clathrin]] mediated [[endocytosis]] of the human [[polyoma virus]] called [[JC virus]], the causative agent of [[progressive multifocal leukoencephalopathy]] (PML), that enters cells like [[oligodendrocyte]]s, [[astrocyte]]s, [[B lymphocytes]], and kidney epithelial cells. These cells need to express both the alpha 2-6–linked [[sialic acid]] component of the 5HT<sub>2A</sub> receptor in order to endocytose JCV.<ref name="pmid15550673">{{cite journal | author = Elphick GF, Querbes W, Jordan JA, Gee GV, Eash S, Manley K, Dugan A, Stanifer M, Bhatnagar A, Kroeze WK, Roth BL, Atwood WJ | title = The human polyomavirus, JCV, uses serotonin receptors to infect cells | journal = Science | volume = 306 | issue = 5700 | pages = 1380–3 | year = 2004 | pmid = 15550673 | doi = 10.1126/science.1103492 | issn = }}</ref> ==References== <!-- --------------------------------------------------------------- See http://en.wikipedia.org/wiki/Wikipedia:Footnotes for a discussion of different citation methods and how to generate footnotes using the <ref> & </ref> tags and the {{Reflist}} template -------------------------------------------------------------------- --> {{Reflist|2}} ==External links== * [http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2320 IUPHAR GPCR Database - 5-HT<sub>2A</sub>] * {{MeshName|5-HT2A+Receptor}} {{G protein-coupled receptors}} {{Cell signaling}} [[Category:Signal transduction]] [[Category:G protein coupled receptors]] <!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. --> {{PBB_Controls | update_page = yes | require_manual_inspection = no | update_protein_box = yes | update_summary = no | update_citations = no }}