5-HT2B receptor

5-hidroksitriptaminski (serotoninski) receptor 2B
Identifikatori
Simboli	HTR2B; 5-HT(2B); 5-HT2B
Vanjski ID	OMIM: 601122 MGI: 109323 HomoloGene: 55492 IUPHAR: 5-HT2B GeneCards: HTR2B Gene
Ontologija gena Molekularna funkcija • aktivnost rodopsinu-sličnog receptora • receptorska aktivnost • aktivnost serotoninskog receptora Celularna komponenta • integralno sa ćelijskom membranom • membrana Biološki proces • prenos signala • G-proteinska signalizacija, spregnuta sa IP3 sekundarnim glasnikom (aktivacija fosfolipaze C) • razvoj srca • cirkulacija • pozitivna regulacija I-kapaB kinaze/NF-kapaB kaskade
Pregled RNK izražavanja
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]

Funkcija

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-HT_2B receptor učestvuje u:

• CNS: presinaptičkoj inhibiciji, utiče na ponašanje^[3]
• Pulmonarna vazokonstrikcija^[4]
• 5-HT_2B receptor reguliše srčanu strukturu i funkciju. Demonstrirano je da dolazi do abnormalnog srčanog razvoja kod miševa bez 5-HT_2B receptora.^[5] Stimulacija 5-HT_2B receptora može da dovede do patološke proliferacije fibroblasta srčanih sudova,^[6] koja kod hronične prekomerne stimulacije može da dovede do ozbiljne valvulopatije. Za 5-HT_2B receptore je nedavno pokazano da su prekomerno izraženi u human obolelom srcu, i za antagoniste 5-HT_2B receptora je nađeno da sprečavanju angiotenzinom II ili beta-adrenergičkim agonistima-indukovanu patološku srčanu hipertropiju kod miševa.^[7][8][9]
• 5-HT_2B 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]

Ligandi

Mali broj visoko selektivnih liganda 5-HT_2B receptora je poznat, a isto tako i brojna potentna neselektivna jedinjenja su dostupna, posebno agensi koji deluju i na 5-HT_2C receptor. Istraživanja u ovoj oblasti su bila ograničena kardiotoksičnošću 5HT_2B agonista, i nedostatkom jasno definisane terapeutske primene 5HT_2B 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-HT_2A, potentan agonist 5-HT_2B i 5-HT_2C receptora
• VER-3323: selektivan za 5-HT_2B/2C u odnosu na 5-HT_2A
• α-Methyl-5-HT - umereno selektivan u odnosu na 5-HT_2A i 5-HT_2C

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-HT_2A / 5-HT_2B antagonist)
• Lisurid (primarno dopaminski agonist, ali deluje i kao 5-HT_2B antagonist)^[19]
• Tegaserod (primarno 5-HT₄ agonist, ali isto tako 5-HT_2B antagonist)^[20]
• RS-127,445:^[21] visok afinitet; selektivan u odnosu na druge 5-HTR tipove; oralno bioraspoloživ.
• SDZ SER-082: mešoviti 5-HT_2B/2C antagonist
• EGIS-7625: visoko selektivan u odnosu na 5-HT_2A^[22]
• PRX-08066
• SB-200,646
• SB-204,741
• SB-206,553: mešoviti 5-HT_2B / 5-HT_2C antagonist i PAM na α7 nAChR^[23]
• SB-215,505^[24]
• SB-228,357
• LY-272,015

Vidi još

• 5-HT receptor

Референце

1. „Entrez Gene: HTR_2B 5-hydroxytryptamine (serotonin) receptor 2B”. 
2. Schmuck K, Ullmer C, Engels P, Lübbert H (1994). „Cloning and functional characterization of the human 5-HT_2B serotonin receptor”. FEBS Lett. 342 (1): 85—90. PMID 8143856. doi:10.1016/0014-5793(94)80590-3. 
3. Doly S, Valjent E, Setola V, Callebert J, Hervé D, Launay JM, Maroteaux L (2008). „Serotonin 5-HT_2B receptors are required for 3,4-methylenedioxymethamphetamine-induced hyperlocomotion and 5-HT release in vivo and in vitro”. J. Neurosci. 28 (11): 2933—40. PMID 18337424. doi:10.1523/JNEUROSCI.5723-07.2008. 
4. Launay JM, Hervé P, Peoc'h K, Tournois C, Callebert J, Nebigil CG, Etienne N, Drouet L, Humbert M, Simonneau G, Maroteaux L (2002). „Function of the serotonin 5-hydroxytryptamine 2B receptor in pulmonary hypertension”. Nat. Med. 8 (10): 1129—35. PMID 12244304. doi:10.1038/nm764. 
5. Nebigil CG, Hickel P, Messaddeq N, Vonesch JL, Douchet MP, Monassier L, György K, Matz R, Andriantsitohaina R, Manivet P, Launay JM, Maroteaux L (2001). „Ablation of serotonin 5-HT(2B) receptors in mice leads to abnormal cardiac structure and function”. Circulation. 103 (24): 2973—9. PMID 11413089. 
6. Elangbam CS, Job LE, Zadrozny LM, Barton JC, Yoon LW, Gates LD, Slocum N (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. PMID 18511249. doi:10.1016/j.etp.2008.03.005. 
7. Jaffré F, Callebert J, Sarre A, Etienne N, Nebigil CG, Launay JM, Maroteaux L, Monassier L (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. PMID 15302781. doi:10.1161/01.CIR.0000139856.20505.57. 
8. Monassier L, Laplante MA, Jaffré F, Bousquet P, Maroteaux L, de Champlain J (2008). „Serotonin 5-HT(2B) receptor blockade prevents reactive oxygen species-induced cardiac hypertrophy in mice”. Hypertension. 52 (2): 301—7. PMID 18591460. doi:10.1161/HYPERTENSIONAHA.107.105551. 
9. Jaffré F, Bonnin P, Callebert J, Debbabi H, Setola V, Doly S, Monassier L, Mettauer B, Blaxall BC, Launay JM, Maroteaux L (2008). „Serotonin and Angiotensin Receptors in Cardiac Fibroblasts Coregulate Adrenergic-Dependent Cardiac Hypertrophy”. Circ. Res. 104 (1): 113—23. PMID 19023134. doi:10.1161/CIRCRESAHA.108.180976. 
10. Callebert J, Esteve JM, Hervé P, Peoc'h K, Tournois C, Drouet L, Launay JM, Maroteaux L (2006). „Evidence for a control of plasma serotonin levels by 5-hydroxytryptamine(2B) receptors in mice”. J. Pharmacol. Exp. Ther. 317 (2): 724—31. PMID 16461587. doi:10.1124/jpet.105.098269. 
11. Doly S, Valjent E, Setola V, Callebert J, Hervé D, Launay JM, Maroteaux L (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. PMID 18337424. doi:10.1523/JNEUROSCI.5723-07.2008. 
12. Diaz SL, Maroteaux L (2011). „Implication of 5-HT(2B) receptors in the serotonin syndrome”. Neuropharmacology. PMID 21277875. doi:10.1016/j.neuropharm.2011.01.025. 
13. Schuhmacher M (2007). „[Chiral arylmethoxytryptamines as 5-HT_2B-receptor antagonists: synthesis, analysis and in-vitro pharmacology] (German)” (PDF). Ph.D. Dissertation. University of Regensburg: 6—17. Архивирано из оригинала (PDF) 18. 07. 2011. г. Приступљено 11. 08. 2008. 
14. Porter, RH; KR, Benwell; Lamb H; et al. (1999). „Functional characterization of agonists at recombinant human 5-HT_2A, 5-HT_2B and 5-HT_2C receptors in CHO-K1 cells”. Br. J. Pharmacol. 128 (1): 13—20. PMC 1571597 . PMID 10498829. doi:10.1038/sj.bjp.0702751. 
15. Kennett GA, Trail B, Bright F (1998). „Anxiolytic-like actions of BW 723C86 in the rat Vogel conflict test are 5-HT2B receptor mediated”. Neuropharmacology. 37 (12): 1603—10. PMID 9886683. doi:10.1016/S0028-3908(98)00115-4. 
16. Setola, Vincent; Sandra J Hufeisen (7. 1. 2003). K Jane Grande-Allen, Ivan Vesely, Richard A Glennon, Bruce Blough, Richard B Rothman, Bryan L Roth. „3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") induces fenfluramine-like proliferative actions on human cardiac valvular interstitial cells in vitro”. Molecular pharmacology. 63 (6): 1223—1229. PMID 12761331. doi:10.1124/mol.63.6.1223. 
17. Ray, TS; Manzoni, Olivier Jacques (2010). Manzoni, Olivier Jacques, ур. „Psychedelics and the human receptorome”. PLoS ONE. 5 (2): e9019. PMC 2814854 . PMID 20126400. doi:10.1371/journal.pone.0009019. 
18. Görnemann T; Hübner H; Gmeiner P; et al. (2008). „Characterization of the molecular fragment that is responsible for agonism of pergolide at serotonin 5-Hydroxytryptamine_2B and 5-Hydroxytryptamine_2A receptors”. J. Pharmacol. Exp. Ther. 324 (3): 1136—45. PMID 18096760. doi:10.1124/jpet.107.133165. 
19. 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. PMID 16614540. doi:10.1097/00002826-200603000-00005. Архивирано из оригинала 11. 03. 2012. г. Приступљено 21. 07. 2011. 
20. Beattie, DT; JA, Smith; Marquess D; et al. (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. PMC 1575425 . PMID 15466450. doi:10.1038/sj.bjp.0705929. 
21. Bonhaus, DW; LA, Flippin; Greenhouse, RJ; et al. (1999). „RS-127445: a selective, high affinity, orally bioavailable 5-HT_2B receptor antagonist”. Br. J. Pharmacol. 127 (5): 1075—82. PMC 1566110 . PMID 10455251. doi:10.1038/sj.bjp.0702632. 
22. 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. PMID 15107597. doi:10.1023/B:CARD.0000015857.96371.43. 
23. Dunlop J; Lock T; Jow B; et al. (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. PMID 19050173. doi:10.1124/jpet.108.146514. 
24. Reavill C, Kettle A, Holland V, Riley G, Blackburn TP (1999). „Attenuation of haloperidol-induced catalepsy by a 5-HT2C receptor antagonist”. Br. J. Pharmacol. 126 (3): 572—4. PMC 1565856 . PMID 10188965. doi:10.1038/sj.bjp.0702350. 

Dodatna literatura

• Raymond, JR; YV, Mukhin; Gelasco A; et al. (2002). „Multiplicity of mechanisms of serotonin receptor signal transduction”. Pharmacol. Ther. 92 (2–3): 179—212. PMID 11916537. doi:10.1016/S0163-7258(01)00169-3. 
• 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. PMID 7926008. doi:10.1016/0014-5793(94)00968-6. 
• 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. PMID 8143856. doi:10.1016/0014-5793(94)80590-3. 
• 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. PMID 8621713. doi:10.1074/jbc.271.6.3141. 
• 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. PMID 8786115. doi:10.1006/geno.1996.0101. 
• 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. PMID 10722792. doi:10.1006/mcpr.1999.0281. 
• 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. PMID 10734074. doi:10.1074/jbc.275.13.9324. 
• 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. PMID 11150294. doi:10.1074/jbc.M008089200. 
• 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. PMID 11859080. doi:10.1074/jbc.M200195200. 
• Borman, RA; NS, Tilford; 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. PMC 1573235 . PMID 11877320. doi:10.1038/sj.bjp.0704571. 
• Strausberg, RL; EA, Feingold; 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. PMC 139241 . PMID 12477932. doi:10.1073/pnas.242603899. 
• 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. PMID 12761501. doi:10.1038/sj.onc.1206406. 
• Slominski A; Pisarchik A; Zbytek B; et al. (2003). „Functional activity of serotoninergic and melatoninergic systems expressed in the skin”. J. Cell. Physiol. 196 (1): 144—53. PMID 12767050. doi:10.1002/jcp.10287. 
• 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. PMC 528928 . PMID 15489334. doi:10.1101/gr.2596504. 
• 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. PMID 15608559. doi:10.1097/00008571-200412000-00003. 
• Hillier, LW; TA, Graves; Fulton, RS; et al. (2005). „Generation and annotation of the DNA sequences of human chromosomes 2 and 4”. Nature. 434 (7034): 724—31. PMID 15815621. doi:10.1038/nature03466. 

Spoljašnje veze

• „5-HT_2B”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Архивирано из оригинала 02. 02. 2017. г.