5-HT2B receptor
(Preusmjereno sa stranice 5-HT2B)
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| 5-hidroksitriptaminski (serotoninski) receptor 2B | |||||||||||
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| Identifikatori | |||||||||||
| Simboli | HTR2B; 5-HT(2B); 5-HT2B | ||||||||||
| Vanjski ID | OMIM: 601122 MGI: 109323 HomoloGene: 55492 IUPHAR: 5-HT2B GeneCards: HTR2B Gene | ||||||||||
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| Pregled RNK izražavanja | |||||||||||
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| podaci | |||||||||||
| Ortolozi | |||||||||||
| Vrsta | Čovek | Miš | |||||||||
| Entrez | 3357 | 15559 | |||||||||
| Ensembl | ENSG00000135914 | ENSMUSG00000026228 | |||||||||
| UniProt | P41595 | Q7TNN4 | |||||||||
| RefSeq (mRNA) | NM_000867 | NM_008311 | |||||||||
| RefSeq (protein) | NP_000858 | NP_032337 | |||||||||
| Lokacija (UCSC) | Chr 2: 231.68 - 231.7 Mb | Chr 1: 87.93 - 87.94 Mb | |||||||||
| PubMed pretraga | [1] | [2] | |||||||||
5-HT2B receptor (5-hidroksitriptaminski (serotoninski) receptor 2B, HTR2B) je 5-HT2 receptor. On je kodiran istoimenim humanim genom.[1][2]
5-HT2 receptori posreduju mnogobrojne centralne i periferne fiziološke funkcije serotonina. Kardiovaskularni efekti obuhvataju kontrakciju krvnih sudova i promene oblika trombocita; efekti na centralni nervni sistem su neuronska senzitizacija na dodirne stimuluse i posredovanje dejstva fenilisopropilamin halucinogena.
5-HT2B receptor učestvuje u:
- CNS: presinaptičkoj inhibiciji, utiče na ponašanje[3]
- Pulmonarna vazokonstrikcija[4]
- 5-HT2B receptor reguliše srčanu strukturu i funkciju. Demonstrirano je da dolazi do abnormalnog srčanog razvoja kod miševa bez 5-HT2B receptora.[5] Stimulacija 5-HT2B receptora može da dovede do patološke proliferacije fibroblasta srčanih sudova,[6] koja kod hronične prekomerne stimulacije može da dovede do ozbiljne valvulopatije. Za 5-HT2B receptore je nedavno pokazano da su prekomerno izraženi u human obolelom srcu, i za antagoniste 5-HT2B receptora je nađeno da sprečavanju angiotenzinom II ili beta-adrenergičkim agonistima-indukovanu patološku srčanu hipertropiju kod miševa.[7][8][9]
- 5-HT2B receptori regulišu otpuštanje serotonina putem serotoninskih transportera. Oni su važni za normalnu fiziološku regulaciju nivoa serotonina u krvnoj plazmi,[10] kao i za abnormalno akutno otpuštanje serotonina proizvedenog lekovima kao što je MDMA.[11][12]
Mali broj visoko selektivnih liganda 5-HT2B receptora je poznat, a isto tako i brojna potentna neselektivna jedinjenja su dostupna, posebno agensi koji deluju i na 5-HT2C receptor. Istraživanja u ovoj oblasti su bila ograničena kardiotoksičnošću 5HT2B agonista, i nedostatkom jasno definisane terapeutske primene 5HT2B antagonista.[13]
Agonisti
- Selektivni
- BW-723C86:[14] znatno funkcionalno selektivan; skoro pun agonist. Anksiolitik in vivo.[15]
- Ro60-0175 [14] funkcionalno selektivan u odnosu na 5-HT2A, potentan agonist 5-HT2B i 5-HT2C receptora
- VER-3323: selektivan za 5-HT2B/2C u odnosu na 5-HT2A
- α-Methyl-5-HT - umereno selektivan u odnosu na 5-HT2A i 5-HT2C
- Neselektivni
- MDMA[16]
- MDA[16]
- MEM[17]
- Pergolid[18]
- Kabergolin
- Norfenfluramin[14]
- Hlorfentermin
- Aminoreks
- mCPP
- Bromo-DragonFLY
- Psilocin
- DMT
- 5-MeO-DMT
Antagonisti
- Sarpogrelat (mešoviti 5-HT2A / 5-HT2B antagonist)
- Lisurid (primarno dopaminski agonist, ali deluje i kao 5-HT2B antagonist)[19]
- Tegaserod (primarno 5-HT4 agonist, ali isto tako 5-HT2B antagonist)[20]
- RS-127,445:[21] visok afinitet; selektivan u odnosu na druge 5-HTR tipove; oralno bioraspoloživ.
- SDZ SER-082: mešoviti 5-HT2B/2C antagonist
- EGIS-7625: visoko selektivan u odnosu na 5-HT2A[22]
- PRX-08066
- SB-200,646
- SB-204,741
- SB-206,553: mešoviti 5-HT2B / 5-HT2C antagonist i PAM na α7 nAChR[23]
- SB-215,505 [24]
- SB-228,357
- LY-272,015
- ↑ „Entrez Gene: HTR2B 5-hydroxytryptamine (serotonin) receptor 2B”.
- ↑ Schmuck K, Ullmer C, Engels P, Lübbert H (March 1994). „Cloning and functional characterization of the human 5-HT2B serotonin receptor”. FEBS Lett. 342 (1): 85–90. DOI:10.1016/0014-5793(94)80590-3. PMID 8143856.
- ↑ Doly S, Valjent E, Setola V, Callebert J, Hervé D, Launay JM, Maroteaux L (March 2008). „Serotonin 5-HT2B receptors are required for 3,4-methylenedioxymethamphetamine-induced hyperlocomotion and 5-HT release in vivo and in vitro”. J. Neurosci. 28 (11): 2933–40. DOI:10.1523/JNEUROSCI.5723-07.2008. PMID 18337424.
- ↑ Launay JM, Hervé P, Peoc'h K, Tournois C, Callebert J, Nebigil CG, Etienne N, Drouet L, Humbert M, Simonneau G, Maroteaux L (October 2002). „Function of the serotonin 5-hydroxytryptamine 2B receptor in pulmonary hypertension”. Nat. Med. 8 (10): 1129–35. DOI:10.1038/nm764. PMID 12244304.
- ↑ Nebigil CG, Hickel P, Messaddeq N, Vonesch JL, Douchet MP, Monassier L, György K, Matz R, Andriantsitohaina R, Manivet P, Launay JM, Maroteaux L (June 2001). „Ablation of serotonin 5-HT(2B) receptors in mice leads to abnormal cardiac structure and function”. Circulation 103 (24): 2973–9. PMID 11413089.
- ↑ Elangbam CS, Job LE, Zadrozny LM, Barton JC, Yoon LW, Gates LD, Slocum N (August 2008). „5-hydroxytryptamine (5HT)-induced valvulopathy: compositional valvular alterations are associated with 5HT2B receptor and 5HT transporter transcript changes in Sprague-Dawley rats”. Exp. Toxicol. Pathol. 60 (4–5): 253–62. DOI:10.1016/j.etp.2008.03.005. PMID 18511249.
- ↑ Jaffré F, Callebert J, Sarre A, Etienne N, Nebigil CG, Launay JM, Maroteaux L, Monassier L (August 2004). „Involvement of the serotonin 5-HT2B receptor in cardiac hypertrophy linked to sympathetic stimulation: control of interleukin-6, interleukin-1beta, and tumor necrosis factor-alpha cytokine production by ventricular fibroblasts”. Circulation 110 (8): 969–74. DOI:10.1161/01.CIR.0000139856.20505.57. PMID 15302781.
- ↑ Monassier L, Laplante MA, Jaffré F, Bousquet P, Maroteaux L, de Champlain J (August 2008). „Serotonin 5-HT(2B) receptor blockade prevents reactive oxygen species-induced cardiac hypertrophy in mice”. Hypertension 52 (2): 301–7. DOI:10.1161/HYPERTENSIONAHA.107.105551. PMID 18591460.
- ↑ Jaffré F, Bonnin P, Callebert J, Debbabi H, Setola V, Doly S, Monassier L, Mettauer B, Blaxall BC, Launay JM, Maroteaux L (November 2008). „Serotonin and Angiotensin Receptors in Cardiac Fibroblasts Coregulate Adrenergic-Dependent Cardiac Hypertrophy”. Circ. Res. 104 (1): 113–23. DOI:10.1161/CIRCRESAHA.108.180976. PMID 19023134.
- ↑ Callebert J, Esteve JM, Hervé P, Peoc'h K, Tournois C, Drouet L, Launay JM, Maroteaux L (May 2006). „Evidence for a control of plasma serotonin levels by 5-hydroxytryptamine(2B) receptors in mice”. J. Pharmacol. Exp. Ther. 317 (2): 724–31. DOI:10.1124/jpet.105.098269. PMID 16461587.
- ↑ Doly S, Valjent E, Setola V, Callebert J, Hervé D, Launay JM, Maroteaux L (March 2008). „Serotonin 5-HT2B receptors are required for 3,4-methylenedioxymethamphetamine-induced hyperlocomotion and 5-HT release in vivo and in vitro”. J. Neurosci. 28 (11): 2933–40. DOI:10.1523/JNEUROSCI.5723-07.2008. PMID 18337424.
- ↑ Diaz SL, Maroteaux L (January 2011). „Implication of 5-HT(2B) receptors in the serotonin syndrome”. Neuropharmacology. DOI:10.1016/j.neuropharm.2011.01.025. PMID 21277875.
- ↑ Schuhmacher M (2007). [Chiral arylmethoxytryptamines as 5-HT2B-receptor antagonists: synthesis, analysis and in-vitro pharmacology (German)]. Ph.D. Dissertation. University of Regensburg. pp. pages 6–17. Arhivirano iz originala na datum 2011-07-18. Pristupljeno 2008-08-11.
- ↑ 14,0 14,1 14,2 Porter RH, Benwell KR, Lamb H, et al. (1999). „Functional characterization of agonists at recombinant human 5-HT2A, 5-HT2B and 5-HT2C receptors in CHO-K1 cells”. Br. J. Pharmacol. 128 (1): 13–20. DOI:10.1038/sj.bjp.0702751. PMC 1571597. PMID 10498829.
- ↑ Kennett GA, Trail B, Bright F (December 1998). „Anxiolytic-like actions of BW 723C86 in the rat Vogel conflict test are 5-HT2B receptor mediated”. Neuropharmacology 37 (12): 1603–10. DOI:10.1016/S0028-3908(98)00115-4. PMID 9886683.
- ↑ 16,0 16,1 Setola, Vincent; Sandra J Hufeisen, K Jane Grande-Allen, Ivan Vesely, Richard A Glennon, Bruce Blough, Richard B Rothman, Bryan L Roth (2003-01-07). „3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") induces fenfluramine-like proliferative actions on human cardiac valvular interstitial cells in vitro”. Molecular pharmacology 63 (6): 1223–1229. DOI:10.1124/mol.63.6.1223. PMID 12761331.
- ↑ Ray TS; Manzoni, Olivier Jacques (2010). Manzoni, Olivier Jacques. ur. „Psychedelics and the human receptorome”. PLoS ONE 5 (2): e9019. DOI:10.1371/journal.pone.0009019. PMC 2814854. PMID 20126400.
- ↑ Görnemann T, Hübner H, Gmeiner P, et al. (2008). „Characterization of the molecular fragment that is responsible for agonism of pergolide at serotonin 5-Hydroxytryptamine2B and 5-Hydroxytryptamine2A receptors”. J. Pharmacol. Exp. Ther. 324 (3): 1136–45. DOI:10.1124/jpet.107.133165. PMID 18096760.
- ↑ Hofmann C, Penner U, Dorow R, Pertz HH, Jähnichen S, Horowski R, Latté KP, Palla D, Schurad B (2006). „Lisuride, a dopamine receptor agonist with 5-HT2B receptor antagonist properties: absence of cardiac valvulopathy adverse drug reaction reports supports the concept of a crucial role for 5-HT2B receptor agonism in cardiac valvular fibrosis”. Clin Neuropharmacol 29 (2): 80–6. DOI:10.1097/00002826-200603000-00005. PMID 16614540. Arhivirano iz originala na datum 2012-03-11. Pristupljeno 2014-05-02.
- ↑ Beattie DT, Smith JA, Marquess D, et al. (November 2004). „The 5-HT4 receptor agonist, tegaserod, is a potent 5-HT2B receptor antagonist in vitro and in vivo”. Br. J. Pharmacol. 143 (5): 549–60. DOI:10.1038/sj.bjp.0705929. PMC 1575425. PMID 15466450.
- ↑ Bonhaus DW, Flippin LA, Greenhouse RJ, et al. (1999). „RS-127445: a selective, high affinity, orally bioavailable 5-HT2B receptor antagonist”. Br. J. Pharmacol. 127 (5): 1075–82. DOI:10.1038/sj.bjp.0702632. PMC 1566110. PMID 10455251.
- ↑ Kovács A, Gacsályi I, Wellmann J, et al. (2003). „Effects of EGIS-7625, a selective and competitive 5-HT2B receptor antagonist”. Cardiovasc Drugs Ther 17 (5–6): 427–34. DOI:10.1023/B:CARD.0000015857.96371.43. PMID 15107597.
- ↑ Dunlop J, Lock T, Jow B, et al. (March 2009). „Old and new pharmacology: positive allosteric modulation of the alpha7 nicotinic acetylcholine receptor by the 5-hydroxytryptamine(2B/C) receptor antagonist SB-206553 (3,5-dihydro-5-methyl-N-3-pyridinylbenzo[1,2-b:4,5-b'di pyrrole-1(2H)-carboxamide)”]. J. Pharmacol. Exp. Ther. 328 (3): 766–76. DOI:10.1124/jpet.108.146514. PMID 19050173.
- ↑ Reavill C, Kettle A, Holland V, Riley G, Blackburn TP (February 1999). „Attenuation of haloperidol-induced catalepsy by a 5-HT2C receptor antagonist”. Br. J. Pharmacol. 126 (3): 572–4. DOI:10.1038/sj.bjp.0702350. PMC 1565856. PMID 10188965.
- Raymond JR, Mukhin YV, Gelasco A, et al. (2002). „Multiplicity of mechanisms of serotonin receptor signal transduction”. Pharmacol. Ther. 92 (2–3): 179–212. DOI:10.1016/S0163-7258(01)00169-3. PMID 11916537.
- Bonhaus DW, Bach C, DeSouza A, et al. (1995). „The pharmacology and distribution of human 5-hydroxytryptamine2B (5-HT2B) receptor gene products: comparison with 5-HT2A and 5-HT2C receptors”. Br. J. Pharmacol. 115 (4): 622–8. PMC 1908489. PMID 7582481.
- Choi DS, Birraux G, Launay JM, Maroteaux L (1994). „The human serotonin 5-HT2B receptor: pharmacological link between 5-HT2 and 5-HT1D receptors”. FEBS Lett. 352 (3): 393–9. DOI:10.1016/0014-5793(94)00968-6. PMID 7926008.
- Kursar JD, Nelson DL, Wainscott DB, Baez M (1994). „Molecular cloning, functional expression, and mRNA tissue distribution of the human 5-hydroxytryptamine2B receptor”. Mol. Pharmacol. 46 (2): 227–34. PMID 8078486.
- Schmuck K, Ullmer C, Engels P, Lübbert H (1994). „Cloning and functional characterization of the human 5-HT2B serotonin receptor”. FEBS Lett. 342 (1): 85–90. DOI:10.1016/0014-5793(94)80590-3. PMID 8143856.
- Launay JM, Birraux G, Bondoux D, et al. (1996). „Ras involvement in signal transduction by the serotonin 5-HT2B receptor”. J. Biol. Chem. 271 (6): 3141–7. DOI:10.1074/jbc.271.6.3141. PMID 8621713.
- Le Coniat M, Choi DS, Maroteaux L, et al. (1996). „The 5-HT2B receptor gene maps to 2q36.3-2q37.1”. Genomics 32 (1): 172–3. DOI:10.1006/geno.1996.0101. PMID 8786115.
- Kim SJ, Veenstra-VanderWeele J, Hanna GL, et al. (2000). „Mutation screening of human 5-HT(2B)receptor gene in early-onset obsessive-compulsive disorder”. Mol. Cell. Probes 14 (1): 47–52. DOI:10.1006/mcpr.1999.0281. PMID 10722792.
- Manivet P, Mouillet-Richard S, Callebert J, et al. (2000). „PDZ-dependent activation of nitric-oxide synthases by the serotonin 2B receptor”. J. Biol. Chem. 275 (13): 9324–31. DOI:10.1074/jbc.275.13.9324. PMID 10734074.
- Becamel C, Figge A, Poliak S, et al. (2001). „Interaction of serotonin 5-hydroxytryptamine type 2C receptors with PDZ10 of the multi-PDZ domain protein MUPP1”. J. Biol. Chem. 276 (16): 12974–82. DOI:10.1074/jbc.M008089200. PMID 11150294.
- Manivet P, Schneider B, Smith JC, et al. (2002). „The serotonin binding site of human and murine 5-HT2B receptors: molecular modeling and site-directed mutagenesis”. J. Biol. Chem. 277 (19): 17170–8. DOI:10.1074/jbc.M200195200. PMID 11859080.
- Borman RA, Tilford NS, Harmer DW, et al. (2002). „5-HT(2B) receptors play a key role in mediating the excitatory effects of 5-HT in human colon in vitro”. Br. J. Pharmacol. 135 (5): 1144–51. DOI:10.1038/sj.bjp.0704571. PMC 1573235. PMID 11877320.
- 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): 16899–903. DOI:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Matsuda A, Suzuki Y, Honda G, et al. (2003). „Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways”. Oncogene 22 (21): 3307–18. DOI:10.1038/sj.onc.1206406. PMID 12761501.
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- 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): 2121–7. DOI:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Lin Z, Walther D, Yu XY, et al. (2005). „The human serotonin receptor 2B: coding region polymorphisms and association with vulnerability to illegal drug abuse”. Pharmacogenetics 14 (12): 805–11. DOI:10.1097/00008571-200412000-00003. PMID 15608559.
- Hillier LW, Graves TA, Fulton RS, et al. (2005). „Generation and annotation of the DNA sequences of human chromosomes 2 and 4”. Nature 434 (7034): 724–31. DOI:10.1038/nature03466. PMID 15815621.