HTR2A

S Wikipedije, slobodne enciklopedije
Idi na navigaciju Idi na pretragu
HTR2A
5ht2a.jpg
Identifikatori
AliasiHTR2A
Vanjski ID-jeviOMIM: 182135 MGI: 109521 HomoloGene: 68073 GeneCards: HTR2A
Lokacija gena (čovjek)
Hromosom 13 (čovjek)
Hrom.Hromosom 13 (čovjek)[1]
Hromosom 13 (čovjek)
Genomska lokacija za HTR2A
Genomska lokacija za HTR2A
Bend13q14.2Početak46,831,546 bp[1]
Kraj46,897,076 bp[1]
Obrazac RNK ekspresije
PBB GE HTR2A 211616 s at fs.png

PBB GE HTR2A 207135 at fs.png
Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija 1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding
G protein-coupled receptor activity
virus receptor activity
signal transducer activity
G-protein alpha-subunit binding
G protein-coupled serotonin receptor activity
serotonin binding
neurotransmitter receptor activity
GO:0001948, GO:0016582 protein binding
GO:0032403 protein-containing complex binding
Ćelijska komponenta citoplazma
integral component of membrane
citosol
projekcija ćelije
membrana
cell body fiber
integral component of plasma membrane
dendritic shaft
Akson
neuronal cell body
Kaveole
GO:0016023 citoplazmatska vezikula
Ćelijska membrana
dendrit
glutamatergic synapse
integral component of postsynaptic membrane
integral component of presynaptic membrane
Biološki proces detection of mechanical stimulus involved in sensory perception of pain
release of sequestered calcium ion into cytosol
regulation of dopamine secretion
phospholipase C-activating serotonin receptor signaling pathway
urinary bladder smooth muscle contraction
positive regulation of MAP kinase activity
behavioral response to cocaine
positive regulation of cytosolic calcium ion concentration
positive regulation of kinase activity
positive regulation of phosphatidylinositol biosynthetic process
GO:0010260 Starenje
cellular calcium ion homeostasis
Ćelijska smrt
Memorija
activation of phospholipase C activity
detection of temperature stimulus involved in sensory perception of pain
protein localization to cytoskeleton
Spavanje
positive regulation of vasoconstriction
positive regulation of cell population proliferation
negative regulation of potassium ion transport
positive regulation of ERK1 and ERK2 cascade
artery smooth muscle contraction
positive regulation of peptidyl-tyrosine phosphorylation
viral entry into host cell
phosphatidylinositol 3-kinase signaling
sensory perception of pain
temperature homeostasis
GO:0022415 viral process
positive regulation of fat cell differentiation
positive regulation of glycolytic process
negative regulation of synaptic transmission, glutamatergic
GO:0072468 signal transduction
chemical synaptic transmission
serotonin receptor signaling pathway
phospholipase C-activating G protein-coupled receptor signaling pathway
G protein-coupled receptor signaling pathway
GO:0035737 behavior
regulation of synaptic vesicle exocytosis
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez
Ensembl
UniProt
RefSeq (mRNK)

NM_001165947
NM_000621
NM_001378924

NM_172812

RefSeq (bjelančevina)

NP_000612
NP_001159419
NP_001365853

NP_766400

Lokacija (UCSC)Chr 13: 46.83 – 46.9 Mbn/a
PubMed pretraga[2][3]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

Receptor 5-HT2A je podtip receptora5-HT2 porodice serotononskih G protein-spregnutih receptora (GPCR).[4] Recweptor 5-HT2A je receptor ćelijske površine.[5] 5-HT je skraćenica za 5-hidroksi-triptamin, koji je serotonin. Ovo je glavni podtip ekscitacijskog receptora među GPCR za serotonin, iako 5-HT2A također može imati inhibitorni učinak[6] na određenim područjima kao što su vizuelni i orbitofrontalni korteks.[7] Ovaj receptor je prvi put zapažen po svom značaju kao meta serotonergični psihodelični lijekovi kao što su LSD i psilocibinska gljiva. Kasnije se vratio na vidjelo jer je utvrđeno da je barem djelomično posredovao u djelovanju mnogih antipsihotičnih lijekova, posebno atipskih.

Smanjena regulacija postsinapsnihih receptora 5-HT2A je adaptivni proces izazvan hroničnom primjenom selektivnih inhibitora preuzimanja serotonina (SSRI) i atipskih antipsihotika. Samoubilački i na drugi način depresivni pacijenti imali su više receptora 5-HT2A od normalnih pacijenata. Ovi nalazi ukazuju na to da je postsinapsna prekomjerna gustoća 5-HT2A uključena u patogenezu depresije.[8]

Paradoksalna podregulacija receptora 5-HT2A može se primijetiti s nekoliko antagonista 5-HT 2A.[9] Prema tome, umjesto tolerancije, od antagoniste 5-HT2A očekivala bi se reverzna tolerancija. Međutim, na ovom mjestu postoji barem jedan antagonist za koji je pokazano da poboljšava receptore 5-HT2A.[10] Osim toga, nekoliko drugih antagonista možda neće uticati na broj receptora 5-HT2A.[11] Ipak, nadregulacija je prije izuzetak nego pravilo. Niti tolerancija niti odskok ne primjećuju se kod ljudi s obzirom na SWS koji promovira efekte antagonista 5-HT2A.[12]

Aminokiselinska sekvenca[uredi | uredi izvor]

Dužina polipeptidnog lanca je 471 aminokiselina, a molekulska težina 52.603 Da.[13]

1020304050
MDILCEENTSLSSTTNSLMQLNDDTRLYSNDFNSGEANTSDAFNWTVDSE
NRTNLSCEGCLSPSCLSLLHLQEKNWSALLTAVVIILTIAGNILVIMAVS
LEKKLQNATNYFLMSLAIADMLLGFLVMPVSMLTILYGYRWPLPSKLCAV
WIYLDVLFSTASIMHLCAISLDRYVAIQNPIHHSRFNSRTKAFLKIIAVW
TISVGISMPIPVFGLQDDSKVFKEGSCLLADDNFVLIGSFVSFFIPLTIM
VITYFLTIKSLQKEATLCVSDLGTRAKLASFSFLPQSSLSSEKLFQRSIH
REPGSYTGRRTMQSISNEQKACKVLGIVFFLFVVMWCPFFITNIMAVICK
ESCNEDVIGALLNVFVWIGYLSSAVNPLVYTLFNKTYRSAFSRYIQCQYK
ENKKPLQLILVNTIPALAYKSSQLQMGQKKNSKQDAKTTDNDCSMVALGK
QHSEEASKDNSDGVNEKVSCV
Simboli

Distribucija[uredi | uredi izvor]

5-HT2A je široko eksprimiran u centralnom nervnom sistemu (CNS). Ispolava se u blizini većine područja bogatih serotonergijskim terminalima, uključujući neokorteks (uglavnom prefrontalni, parietalni i somatosenzorni korteks) i olfaktorni tuberkulom. Posebno visoke koncentracije ovog receptora na apikalni dendritima piramidnih ćelija u sloju V korteksa mogu modulirati kognitivne procese, radnu memoriju i pažnju[14][15][16] pojačavanjem oslobađanja glutamata, nakon čega slijedi složen raspon interakcija s 5-HT1A,[17] GABAA,[18] adenozin A1,[19] AMPA,[20] mGluR2/3,[21] mGlu5,[22] i receptori OX2.[23][24] U malom mozgu pacova, protein je takođe pronađen u Golgijevim ćelijama zrnastog sloja,[25] i u Purkinjeovim ćelijama.[26][27]

Na periferiji je visoko eksprimiran u trombocitima i mnogim tipovima ćelija kardiovaskularnog sistema, u fibroblastima i u neuronima perifernog nervnog sistema. Osim toga, ekspresija iRNK za 5-HT2A primijećena je kod ljudskih monocita.[28] Distribucija agonista receptora 5-HT2A/2C u cijelom tijelu, [11C] Cimbi-36 pokazuje unos u nekoliko unutrašnjih organa i smeđe masno tkivo (BAT), ali nije jasno predstavlja li to specifično vezivanje za receptore 5-HT2A.[29]

Signalna kaskada[uredi | uredi izvor]

Poznato je da se receptor 5-HT2A prvenstveno spaja sa q putem transdukcije signala. Nakon stimulacije receptora preko agonista, Gαq i β-γ podjedinice disociraju kako bi pokrenuli nizvodne efektorske putove. Gα q stimulira aktivnost fosfolipaza C (PLC), što kasnije podstiče oslobađanje diacilglicerola (DAG) i inozitol-trifosfata (IP3), koji zauzvrat stimuliraju aktivnost protein-kinaza C (PKC) i oslobađanje Ca2+.[30]

Efekti[uredi | uredi izvor]

Fiziološki procesi posredovani receptorom uključuju:

Genetika[uredi | uredi izvor]

Receptori 5-HT2A kodirani su genom HTR2A . Kod ljudi gen se nalazi na hromozomu 13. Gen se ranije zvao samo HTR2 do opisa dva povezana gena HTR2B i HTR2C. Za HTR2A je identificirano nekoliko zanimljivih polimorfizama): A-1438G (rs6311), C102T (rs6313) i His452Tyr (rs6314). Za ovaj gen postoji mnogo više vezanih polimorfizama. U dokumentu iz 2006. godine navedeno ih je 255.[42]

Vjerojatna uloga u fibromialgiji kao polimorfizmi T102C gena 5HT2A bili su česti u pacijenata s fibromialgijom.[43]

Smatra se da se ljudskii gen HTR2A sastoji od tri introna i četiri egzona i da se preklapa s ljudskim genom HTR2A-AS1 ,koji se sastoji od 18 egzona.[44] Postoji više od 200 organizama koji imaju orthologa s ljudskim HTR2A. Najbolje dokumentirani ortolozi za gen HTR2Asu mišji[45] i zebricin.[46] Postoji osam paraloga za gen HTR2A. Poznato je da gen HTR2A stupa u interakciju i aktivira gene za G-proteine kao što su GNA14, GNAI1, GNAI3, GNAQ, i GNAZ.[47] Ove interakcije su kritične za ćelijsku signalizaciju [48][49] i homeostazu [50] imnogih organizama.[51]

U ljudskom moždanom tkivu regulacija HTR2A varira ovisno o regiji: frontalni korteks, amigdala, talamus, moždano stablo i mali mozak. U radu iz 2016. otkrili su da HTR2A prolazi kroz različite prerade, uključujući i alternativnua akceptorska mjesta, preskakanje egzona , rijetku upotrebu egzona i zadržavanje introna.

Mehanizmi regulacije[uredi | uredi izvor]

Postoji nekoliko mehanizama regulacije za gen HTR2A koji je reguliran metilacijom DNK na određenim mjestima vezanja za transkript.[52][53] Ostali mehanizmi za ispravnu regulaciju ekspresije gena postižu se alternativnom preradom. Ovo je kotranskripcijski proces, koji omogućuje generiranje više oblika transkripta iRNK iz jedne kodirajuće jedinice i pojavljuje se kao važna kontrolna tačka za ekspresiju gena. U ovom procesu, egzoni ili introni mogu biti uključeni ili isključeni iz prekursorne-iRNK, što rezultira u više zrelih varijanti iRNK.[54] Ove varijante iRNK rezultiraju različitim izoformama koje mogu imati antagonističke funkcije ili različite obrasce ekspresije, dajući ćelijama plastičnost i prilagodljivost.[55] One study found that the common genetic variant rs6311 regulates expression of HTR2A transcripts containing the extended 5’ UTR.

Jedno istraživanje otkrilo je da uobičajena genetička varijanta rs6311 regulira ekspresiju transkripata HTR2A koji sadrže prošireni 5' UTR.

Pridruženi psihijatrijski poremećaji[uredi | uredi izvor]

Nekoliko studija je pokazalo veze između polimorfizma -1438G/A i poremećaja raspoloženja, kao što je bipolarni poremećaj[56] i glavni depresivni poremećaj.[57]

Između polimorfizma T102C i shizofrenije pronađena je slaba veza s omjerom vjerovatnoće od 1,3.[58]

Ovaj polimorfizam je također proučavan u odnosu na pokušaje samoubistva, pri čemu je studija među pokušajima samoubistva otkrila višak genotipova C/C.[59]

Ove pojedinačne studije, međutim, možda ne daju potpunu sliku: pregled iz 2007. koji se bavi učinkom različitih jednonukleotidnih polimorfizama objavljen u odvojenim studijama navodi da su "studije genetičke povezanosti" varijanti gena "HTR2A" s psihijatrijskim poremećajima ] pr kontradiktorne i općenito sa negativnim rezultatima "bez učešća, male ili neopisane uloge genetičke varijante gena".[60]

Polimorfizmi u promotorskom genu, koji kodira rani odgovor na rast 3 (EGR3) povezani su sa shizofrenijom. Studije su pokazale vezu između EGR3 i HTR2A i ponašanja sličnog shizofreniji kod transgenih životinja.[61][62] Exactly how these results translate over to further biopsychological understanding of schizophrenia is still widely debated.[63][64] Postoje neki dokazi da disfunkcija "HTR2A" može uticati na farmakološke intervencije.[65]

Odgovor na liječenje[uredi | uredi izvor]

Čini se da je i genetikčka osnova donekle povezana s količinom nuspojava u liječenju velikog depresivnog poremećaja.[66]

Veze sa zloupotrebom supstanci[uredi | uredi izvor]

Pokazalo se da polimorfizmi receptora 5-HT2A kodirajućem genu HTR2A (rs6313 i s6311) imaju sukobljeneveze sa zloupotrebom alkohola. Naprimjer, prijavljeno je da polimorfizam gena za kodiranje 5-HT2A receptora HTR2A (rs6313) predviđa niže pozitivno očekivano trajanje alkohola u krvi, veću odbijajuću samoefikasnost i manju zloupotrebu alkohola u uzorku od 120 mladih odraslih osoba. Međutim, ovaj polimorfizam nije ublažio veze između impulzivnosti, spoznaje i zloupotrebe alkohola [67] Postoje i oprečni rezultati jer su druge studije otkrile povezanost polimorfizama T102C sa zloupotrebom alkohola.[68][69]

Uticaj lijekova na ekspresiju gena[uredi | uredi izvor]

Postoje neki dokazi da obrasci metilacije mogu doprinijeti relapsu ponašanja kod ljudi koji koriste stimulanse.[70] Kod miševa, psihotropni lijekovi kao što su DOI, LSD, DOM i DOB proizveli su različite obrasce transkripcije među nekoliko različitih regija mozga.

Reference[uredi | uredi izvor]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000102468 - Ensembl, maj 2017
  2. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ Cook EH, Fletcher KE, Wainwright M, Marks N, Yan SY, Leventhal BL (August 1994). "Primary structure of the human platelet serotonin 5-HT2A receptor: identify with frontal cortex serotonin 5-HT2A receptor". Journal of Neurochemistry. 63 (2): 465–9. doi:10.1046/j.1471-4159.1994.63020465.x. PMID 8035173. S2CID 40207336.
  5. ^ a b Kling A (2013). 5-HT2A: a serotonin receptor with a possible role in joint diseases (PDF). Umeå: Umeå Universitet. ISBN 978-91-7459-549-9.
  6. ^ Martin P, Waters N, Schmidt CJ, Carlsson A, Carlsson ML (1998). "Rodent data and general hypothesis: antipsychotic action exerted through 5-HT2A receptor antagonism is dependent on increased serotonergic tone". Journal of Neural Transmission. 105 (4–5): 365–96. doi:10.1007/s007020050064. PMID 9720968. S2CID 20944107.
  7. ^ De Almeida RM, Rosa MM, Santos DM, Saft DM, Benini Q, Miczek KA (May 2006). "5-HT(1B) receptors, ventral orbitofrontal cortex, and aggressive behavior in mice". Psychopharmacology. 185 (4): 441–50. doi:10.1007/s00213-006-0333-3. PMID 16550387. S2CID 33274637.
  8. ^ Eison AS, Mullins UL (1996). "Regulation of central 5-HT2A receptors: a review of in vivo studies". Behavioural Brain Research. 73 (1–2): 177–81. doi:10.1016/0166-4328(96)00092-7. PMID 8788498. S2CID 4048975.
  9. ^ Yadav PN, Kroeze WK, Farrell MS, Roth BL (October 2011). "Antagonist functional selectivity: 5-HT2A serotonin receptor antagonists differentially regulate 5-HT2A receptor protein level in vivo". The Journal of Pharmacology and Experimental Therapeutics. 339 (1): 99–105. doi:10.1124/jpet.111.183780. PMC 3186284. PMID 21737536.
  10. ^ Rinaldi-Carmona M, Congy C, Simiand J, Oury-Donat F, Soubrie P, Breliere JC, Le Fur G (January 1993). "Repeated administration of SR 46349B, a selective 5-hydroxytryptamine2 antagonist, up-regulates 5-hydroxytryptamine2 receptors in mouse brain". Molecular Pharmacology. 43 (1): 84–9. PMID 8423772.
  11. ^ Gray JA, Roth BL (November 2001). "Paradoxical trafficking and regulation of 5-HT(2A) receptors by agonists and antagonists". Brain Research Bulletin. 56 (5): 441–51. doi:10.1016/s0361-9230(01)00623-2. PMID 11750789. S2CID 271925.
  12. ^ Vanover KE, Davis RE (28 July 2010). "Role of 5-HT2A receptor antagonists in the treatment of insomnia". Nature and Science of Sleep. 2: 139–50. doi:10.2147/nss.s6849. PMC 3630942. PMID 23616706.
  13. ^ "UniProt, P28223". Pristupljeno 2017-09-11. CS1 održavanje: nepreporučeni parametar (link)
  14. ^ Aghajanian GK, Marek GJ (April 1999). "Serotonin, via 5-HT2A receptors, increases EPSCs in layer V pyramidal cells of prefrontal cortex by an asynchronous mode of glutamate release". Brain Research. 825 (1–2): 161–71. doi:10.1016/S0006-8993(99)01224-X. PMID 10216183. S2CID 20081913.
  15. ^ Marek GJ, Wright RA, Gewirtz JC, Schoepp DD (2001). "A major role for thalamocortical afferents in serotonergic hallucinogen receptor function in the rat neocortex". Neuroscience. 105 (2): 379–92. doi:10.1016/S0306-4522(01)00199-3. PMID 11672605. S2CID 19764312.
  16. ^ a b Bortolozzi A, Díaz-Mataix L, Scorza MC, Celada P, Artigas F (December 2005). "The activation of 5-HT receptors in prefrontal cortex enhances dopaminergic activity". Journal of Neurochemistry. 95 (6): 1597–607. doi:10.1111/j.1471-4159.2005.03485.x. hdl:10261/33026. PMID 16277612. S2CID 18350703.
  17. ^ Amargós-Bosch M, Bortolozzi A, Puig MV, Serrats J, Adell A, Celada P, Toth M, Mengod G, Artigas F (March 2004). "Co-expression and in vivo interaction of serotonin1A and serotonin2A receptors in pyramidal neurons of prefrontal cortex". Cerebral Cortex. 14 (3): 281–99. doi:10.1093/cercor/bhg128. PMID 14754868.
  18. ^ Feng J, Cai X, Zhao J, Yan Z (September 2001). "Serotonin receptors modulate GABA(A) receptor channels through activation of anchored protein kinase C in prefrontal cortical neurons". The Journal of Neuroscience. 21 (17): 6502–11. doi:10.1523/JNEUROSCI.21-17-06502.2001. PMC 6763081. PMID 11517239.
  19. ^ Marek GJ (June 2009). "Activation of adenosine(1) (A(1)) receptors suppresses head shakes induced by a serotonergic hallucinogen in rats". Neuropharmacology. 56 (8): 1082–7. doi:10.1016/j.neuropharm.2009.03.005. PMC 2706691. PMID 19324062.
  20. ^ Zhang C, Marek GJ (January 2008). "AMPA receptor involvement in 5-hydroxytryptamine2A receptor-mediated pre-frontal cortical excitatory synaptic currents and DOI-induced head shakes". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 32 (1): 62–71. doi:10.1016/j.pnpbp.2007.07.009. PMID 17728034. S2CID 44889209.
  21. ^ Gewirtz JC, Marek GJ (November 2000). "Behavioral evidence for interactions between a hallucinogenic drug and group II metabotropic glutamate receptors". Neuropsychopharmacology. 23 (5): 569–76. doi:10.1016/S0893-133X(00)00136-6. PMID 11027922.
  22. ^ Marek GJ, Zhang C (September 2008). "Activation of metabotropic glutamate 5 (mGlu5) receptors induces spontaneous excitatory synaptic currents in layer V pyramidal cells of the rat prefrontal cortex". Neuroscience Letters. 442 (3): 239–43. doi:10.1016/j.neulet.2008.06.083. PMC 2677702. PMID 18621097.
  23. ^ Lambe EK, Liu RJ, Aghajanian GK (November 2007). "Schizophrenia, hypocretin (orexin), and the thalamocortical activating system". Schizophrenia Bulletin. 33 (6): 1284–90. doi:10.1093/schbul/sbm088. PMC 2779889. PMID 17656637.
  24. ^ Liu RJ, Aghajanian GK (January 2008). "Stress blunts serotonin- and hypocretin-evoked EPSCs in prefrontal cortex: role of corticosterone-mediated apical dendritic atrophy". Proceedings of the National Academy of Sciences of the United States of America. 105 (1): 359–64. Bibcode:2008PNAS..105..359L. doi:10.1073/pnas.0706679105. PMC 2224217. PMID 18172209.
  25. ^ Geurts FJ, De Schutter E, Timmermans JP (June 2002). "Localization of 5-HT2A, 5-HT3, 5-HT5A and 5-HT7 receptor-like immunoreactivity in the rat cerebellum". Journal of Chemical Neuroanatomy. 24 (1): 65–74. doi:10.1016/S0891-0618(02)00020-0. PMID 12084412. S2CID 16510169.
  26. ^ Maeshima T, Shutoh F, Hamada S, Senzaki K, Hamaguchi-Hamada K, Ito R, Okado N (August 1998). "Serotonin2A receptor-like immunoreactivity in rat cerebellar Purkinje cells". Neuroscience Letters. 252 (1): 72–4. doi:10.1016/S0304-3940(98)00546-1. PMID 9756362. S2CID 28549709.
  27. ^ Maeshima T, Shiga T, Ito R, Okado N (December 2004). "Expression of serotonin2A receptors in Purkinje cells of the developing rat cerebellum". Neuroscience Research. 50 (4): 411–7. doi:10.1016/j.neures.2004.08.010. PMID 15567478. S2CID 5772490.
  28. ^ Dürk T, Panther E, Müller T, Sorichter S, Ferrari D, Pizzirani C, et al. (May 2005). "5-Hydroxytryptamine modulates cytokine and chemokine production in LPS-primed human monocytes via stimulation of different 5-HTR subtypes". International Immunology. 17 (5): 599–606. doi:10.1093/intimm/dxh242. PMID 15802305.
  29. ^ Johansen A, Holm S, Dall B, Keller S, Kristensen JL, Knudsen GM, Hansen HD (July 2019). "2A receptor agonist Cimbi-36 labeled with carbon-11 in two positions". EJNMMI Research. 9 (1): 71. doi:10.1186/s13550-019-0527-4. PMC 6669221. PMID 31367837.
  30. ^ 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 (January 2007). "Functional selectivity and classical concepts of quantitative pharmacology". The Journal of Pharmacology and Experimental Therapeutics. 320 (1): 1–13. doi:10.1124/jpet.106.104463. PMID 16803859. S2CID 447937.
  31. ^ Moreno JL, Holloway T, Albizu L, Sealfon SC, González-Maeso J (April 2011). "Metabotropic glutamate mGlu2 receptor is necessary for the pharmacological and behavioral effects induced by hallucinogenic 5-HT2A receptor agonists". Neuroscience Letters. 493 (3): 76–9. doi:10.1016/j.neulet.2011.01.046. PMC 3064746. PMID 21276828.
  32. ^ Jalal B (November 2018). "The neuropharmacology of sleep paralysis hallucinations: serotonin 2A activation and a novel therapeutic drug". Psychopharmacology. 235 (11): 3083–3091. doi:10.1007/s00213-018-5042-1. PMC 6208952. PMID 30288594.
  33. ^ Yu B, Becnel J, Zerfaoui M, Rohatgi R, Boulares AH, Nichols CD (November 2008). "Serotonin 5-hydroxytryptamine(2A) receptor activation suppresses tumor necrosis factor-alpha-induced inflammation with extraordinary potency". The Journal of Pharmacology and Experimental Therapeutics. 327 (2): 316–23. doi:10.1124/jpet.108.143461. PMID 18708586. S2CID 25374241.
  34. ^ Nau F, Yu B, Martin D, Nichols CD (2013). "Serotonin 5-HT2A receptor activation blocks TNF-α mediated inflammation in vivo". PLOS ONE. 8 (10): e75426. Bibcode:2013PLoSO...875426N. doi:10.1371/journal.pone.0075426. PMC 3788795. PMID 24098382.
  35. ^ Van de Kar LD, Javed A, Zhang Y, Serres F, Raap DK, Gray TS (May 2001). "5-HT2A receptors stimulate ACTH, corticosterone, oxytocin, renin, and prolactin release and activate hypothalamic CRF and oxytocin-expressing cells". The Journal of Neuroscience. 21 (10): 3572–9. doi:10.1523/JNEUROSCI.21-10-03572.2001. PMC 6762485. PMID 11331386.
  36. ^ Zhang Y, Damjanoska KJ, Carrasco GA, Dudas B, D'Souza DN, Tetzlaff J, Garcia F, Hanley NR, Scripathirathan K, Petersen BR, Gray TS, Battaglia G, Muma NA, Van de Kar LD (November 2002). "Evidence that 5-HT2A receptors in the hypothalamic paraventricular nucleus mediate neuroendocrine responses to (-)DOI". The Journal of Neuroscience. 22 (21): 9635–42. doi:10.1523/JNEUROSCI.22-21-09635.2002. PMC 6758011. PMID 12417689.
  37. ^ Harvey JA (2003). "Role of the serotonin 5-HT(2A) receptor in learning". Learning & Memory. 10 (5): 355–62. doi:10.1101/lm.60803. PMC 218001. PMID 14557608.
  38. ^ Williams GV, Rao SG, Goldman-Rakic PS, Foresta M, Ropolo M, Degan P, Pettinati I, Kow YW, Damonte G, Poggi A, Frosina G (March 2010). "Defective repair of 5-hydroxy-2'-deoxycytidine in Cockayne syndrome cells and its complementation by Escherichia coli formamidopyrimidine DNA glycosylase and endonuclease III". Free Radical Biology & Medicine. 48 (5): 681–90. doi:10.1016/j.freeradbiomed.2009.12.007. PMC 6758292. PMID 11923449.
  39. ^ Passier A, van Puijenbroek E (2005). "Mirtazapine-induced arthralgia". Br J Clin Pharmacol. 60 (5): 570–2. doi:10.1111/j.1365-2125.2005.02481.x. PMC 1884949. PMID 16236049.
  40. ^ Adwan MH (2016). "An update on drug-induced arthritis". Rheumatol Int. 36 (8): 1089–97. doi:10.1007/s00296-016-3462-y. PMID 27000044. S2CID 25401280.
  41. ^ Herth MM, Knudsen GM (2015). "Current radiosynthesis strategies for 5-HT2A receptor PET tracers". J Labelled Comp Radiopharm. 58 (7): 265–73. doi:10.1002/jlcr.3288. PMID 25997728.
  42. ^ Bonis J, Furlong LI, Sanz F (October 2006). "OSIRIS: a tool for retrieving literature about sequence variants". Bioinformatics. 22 (20): 2567–9. doi:10.1093/bioinformatics/btl421. PMID 16882651. Supplementary material to article
  43. ^ Goldstein AT, Pukall C, Goldstein IL (2020). "Fibromyalgia and Female Sexual Pain Disorders". Female Sexual Pain Disorders: Evaluation and Management (2 izd.). Wiley. ISBN 978-1119482666.
  44. ^ Ruble CL, Smith RM, Calley J, Munsie L, Airey DC, Gao Y, et al. (January 2016). "Genomic structure and expression of the human serotonin 2A receptor gene (HTR2A) locus: identification of novel HTR2A and antisense (HTR2A-AS1) exons". BMC Genetics. 17 (1): 16. doi:10.1186/s12863-015-0325-6. PMC 4702415. PMID 26738766.
  45. ^ Medrihan L, Sagi Y, Inde Z, Krupa O, Daniels C, Peyrache A, Greengard P (August 2017). "Initiation of Behavioral Response to Antidepressants by Cholecystokinin Neurons of the Dentate Gyrus". Neuron. 95 (3): 564–576.e4. doi:10.1016/j.neuron.2017.06.044. PMID 28735749.
  46. ^ Griffin A, Hamling KR, Knupp K, Hong S, Lee LP, Baraban SC (March 2017). "Clemizole and modulators of serotonin signalling suppress seizures in Dravet syndrome". Brain. 140 (3): 669–683. doi:10.1093/brain/aww342. PMC 6075536. PMID 28073790.
  47. ^ Giulietti M, Vivenzio V, Piva F, Principato G, Bellantuono C, Nardi B (July 2014). "How much do we know about the coupling of G-proteins to serotonin receptors?". Molecular Brain. 7 (1): 49. doi:10.1186/s13041-014-0049-y. PMC 4105882. PMID 25011628.
  48. ^ Lal D, May P, Perez-Palma E, Samocha KE, Kosmicki JA, Robinson EB, et al. (March 2020). "Gene family information facilitates variant interpretation and identification of disease-associated genes in neurodevelopmental disorders". Genome Medicine. 12 (1): 28. doi:10.1186/s13073-020-00725-6. PMC 7079346. PMID 32183904.
  49. ^ Gao W, Guo N, Zhao S, Chen Z, Zhang W, Yan F, et al. (November 2020). "HTR2A promotes the development of cardiac hypertrophy by activating PI3K-PDK1-AKT-mTOR signaling". Cell Stress & Chaperones. 25 (6): 899–908. doi:10.1007/s12192-020-01124-x. PMC 7591670. PMID 32519137.
  50. ^ Cao X, Wang Y, Shu D, Qu H, Luo C, Hu X (October 2020). "Food intake-related genes in chicken determined through combinatorial genome-wide association study and transcriptome analysis". Animal Genetics. 51 (5): 741–751. doi:10.1111/age.12980. PMID 32720725.
  51. ^ Garza-Brenner E, Sifuentes-Rincón AM, Randel RD, Paredes-Sánchez FA, Parra-Bracamonte GM, Arellano Vera W, et al. (August 2017). "Association of SNPs in dopamine and serotonin pathway genes and their interacting genes with temperament traits in Charolais cows". Journal of Applied Genetics. 58 (3): 363–371. doi:10.1007/s13353-016-0383-0. PMID 27987181.
  52. ^ Cheah SY, Lawford BR, Young RM, Morris CP, Voisey J (January 2017). "mRNA Expression and DNA Methylation Analysis of Serotonin Receptor 2A (HTR2A) in the Human Schizophrenic Brain". Genes. 8 (1): 14. doi:10.3390/genes8010014. PMC 5295009. PMID 28054990.
  53. ^ Falkenberg VR, Gurbaxani BM, Unger ER, Rajeevan MS (March 2011). "Functional genomics of serotonin receptor 2A (HTR2A): interaction of polymorphism, methylation, expression and disease association". Neuromolecular Medicine. 13 (1): 66–76. doi:10.1007/s12017-010-8138-2. PMC 3044825. PMID 20941551.
  54. ^ Kelemen O, Convertini P, Zhang Z, Wen Y, Shen M, Falaleeva M, Stamm S (February 2013). "Function of alternative splicing". Gene. 514 (1): 1–30. doi:10.1016/j.gene.2012.07.083. PMC 5632952. PMID 22909801.
  55. ^ Wang ET, Ward AJ, Cherone JM, Giudice J, Wang TT, Treacy DJ, et al. (June 2015). "Antagonistic regulation of mRNA expression and splicing by CELF and MBNL proteins". Genome Research. 25 (6): 858–71. doi:10.1101/gr.184390.114. PMC 4448682. PMID 25883322.
  56. ^ Chee IS, Lee SW, Kim JL, Wang SK, Shin YO, Shin SC, Lee YH, Hwang HM, Lim MR (September 2001). "5-HT2A receptor gene promoter polymorphism -1438A/G and bipolar disorder". Psychiatric Genetics. 11 (3): 111–4. doi:10.1097/00041444-200109000-00001. PMID 11702051. S2CID 39214172.
  57. ^ Choi MJ, Lee HJ, Lee HJ, Ham BJ, Cha JH, Ryu SH, Lee MS (2004). "Association between major depressive disorder and the -1438A/G polymorphism of the serotonin 2A receptor gene". Neuropsychobiology. 49 (1): 38–41. doi:10.1159/000075337. PMID 14730199. S2CID 19528052.
  58. ^ Williams J, Spurlock G, McGuffin P, Mallet J, Nöthen MM, Gill M, Aschauer H, Nylander PO, Macciardi F, Owen MJ (May 1996). "Association between schizophrenia and T102C polymorphism of the 5-hydroxytryptamine type 2a-receptor gene. European Multicentre Association Study of Schizophrenia (EMASS) Group". Lancet. 347 (9011): 1294–6. doi:10.1016/s0140-6736(96)90939-3. PMID 8622505. S2CID 8510590.
  59. ^ 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 (July 2008). "Association study of two polymorphisms of the serotonin-2A receptor gene and suicide attempts". American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. 147B (5): 645–9. doi:10.1002/ajmg.b.30642. PMID 18163387. S2CID 31504282.
  60. ^ Serretti A, Drago A, De Ronchi D (2007). "HTR2A gene variants and psychiatric disorders: a review of current literature and selection of SNPs for future studies". Current Medicinal Chemistry. 14 (19): 2053–69. doi:10.2174/092986707781368450. PMID 17691947.
  61. ^ Maple AM, Zhao X, Elizalde DI, McBride AK, Gallitano AL (July 2015). "Htr2a Expression Responds Rapidly to Environmental Stimuli in an Egr3-Dependent Manner". ACS Chemical Neuroscience. 6 (7): 1137–42. doi:10.1021/acschemneuro.5b00031. PMC 4565721. PMID 25857407.
  62. ^ Williams AA, Ingram WM, Levine S, Resnik J, Kamel CM, Lish JR, et al. (September 2012). "Reduced levels of serotonin 2A receptors underlie resistance of Egr3-deficient mice to locomotor suppression by clozapine". Neuropsychopharmacology. 37 (10): 2285–98. doi:10.1038/npp.2012.81. PMC 3422493. PMID 22692564.
  63. ^ Latorre E, Mesonero JE, Harries LW (November 2019). "Alternative splicing in serotonergic system: Implications in neuropsychiatric disorders". Journal of Psychopharmacology. 33 (11): 1352–1363. doi:10.1177/0269881119856546. PMID 31210090.
  64. ^ Spies M, Nasser A, Ozenne B, Jensen PS, Knudsen GM, Fisher PM (November 2020). "Common HTR2A variants and 5-HTTLPR are not associated with human in vivo serotonin 2A receptor levels". Human Brain Mapping. 41 (16): 4518–4528. doi:10.1002/hbm.25138. PMC 7555071. PMID 32697408.
  65. ^ Qesseveur G, Petit AC, Nguyen HT, Dahan L, Colle R, Rotenberg S, et al. (June 2016). "Genetic dysfunction of serotonin 2A receptor hampers response to antidepressant drugs: A translational approach". Neuropharmacology. 105: 142–153. doi:10.1016/j.neuropharm.2015.12.022. PMID 26764241.
  66. ^ Laje G, McMahon FJ (December 2007). "The pharmacogenetics of major depression: past, present, and future". Biological Psychiatry. 62 (11): 1205–7. doi:10.1016/j.biopsych.2007.09.016. PMID 17949692. S2CID 37225993.
  67. ^ Leamy TE, Connor JP, Voisey J, Young RM, Gullo MJ (December 2016). "Alcohol misuse in emerging adulthood: Association of dopamine and serotonin receptor genes with impulsivity-related cognition". Addictive Behaviors. 63: 29–36. doi:10.1016/j.addbeh.2016.05.008. PMID 27399274.
  68. ^ Jakubczyk A, Wrzosek M, Lukaszkiewicz J, Sadowska-Mazuryk J, Matsumoto H, Sliwerska E, et al. (January 2012). "The CC genotype in HTR2A T102C polymorphism is associated with behavioral impulsivity in alcohol-dependent patients". Journal of Psychiatric Research. 46 (1): 44–9. doi:10.1016/j.jpsychires.2011.09.001. PMC 3224206. PMID 21930285.
  69. ^ da Silva Junior FC, Araujo RM, Sarmento AS, de Carvalho MM, Fernandes HF, Yoshioka FK, Pinto GR, Motta FJ, Canalle R (December 2020). "The association of A-1438G and T102C polymorphisms in HTR2A and 120 bp duplication in DRD4 with alcoholic dependence in a northeastern Brazilian male population". Gene Reports. 21: 100889. doi:10.1016/j.genrep.2020.100889.
  70. ^ Land MA, Ramesh D, Miller AL, Pyles RB, Cunningham KA, Moeller FG, Anastasio NC (2020-06-10). "Methylation Patterns of the HTR2A Associate With Relapse-Related Behaviors in Cocaine-Dependent Participants". Frontiers in Psychiatry. 11: 532. doi:10.3389/fpsyt.2020.00532. PMC 7299072. PMID 32587535.

Dopunska literatura[uredi | uredi izvor]

Vanjski linkovi[uredi | uredi izvor]

Šablon:G protein-spregnuti receptori Šablon:Opsesivno -kompulzivni poremećaj Šablon:Halucinogeni Šablon:Hipnotici i sedativi