5-HT2B receptor

Из Википедије, слободне енциклопедије
5-hidroksitriptaminski (serotoninski) receptor 2B
Identifikatori
Simboli HTR2B; 5-HT(2B); 5-HT2B
Vanjski ID OMIM601122 MGI109323 HomoloGene55492 IUPHAR: 5-HT2B GeneCards: HTR2B Gene
Pregled RNK izražavanja
PBB GE HTR2B 206638 at tn.png
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[уреди]

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:

  • 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]

Ligandi[уреди]

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
Neselektivni

Antagonisti

Vidi još[уреди]

Literatura[уреди]

  1. ^ „Entrez Gene: HTR2B 5-hydroxytryptamine (serotonin) receptor 2B“. 
  2. ^ 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. 
  3. ^ 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. 
  4. ^ 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. 
  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 (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. 
  6. ^ 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. 
  7. ^ 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. 
  8. ^ 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. 
  9. ^ 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. 
  10. ^ 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. 
  11. ^ 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. 
  12. ^ 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. 
  13. ^ 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 Приступљено 11. 08. 2008.. 
  14. ^ а б в 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. 
  15. ^ 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. ^ а б Setola, Vincent; Sandra J Hufeisen, K Jane Grande-Allen, Ivan Vesely, Richard A Glennon, Bruce Blough, Richard B Rothman, Bryan L Roth (Jan 7 2003). „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. 
  17. ^ Ray TS; Manzoni, Olivier Jacques (2010). Manzoni, Olivier Jacques. ed. „Psychedelics and the human receptorome“. PLoS ONE 5 (2): e9019. DOI:10.1371/journal.pone.0009019. PMC 2814854. PMID 20126400. 
  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-Hydroxytryptamine2B and 5-Hydroxytryptamine2A receptors“. J. Pharmacol. Exp. Ther. 324 (3): 1136–45. DOI:10.1124/jpet.107.133165. PMID 18096760. 
  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. DOI:10.1097/00002826-200603000-00005. PMID 16614540. 
  20. ^ 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. 
  21. ^ 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. 
  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. DOI:10.1023/B:CARD.0000015857.96371.43. PMID 15107597. 
  23. ^ 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. 
  24. ^ 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. 

Dodatna literatura[уреди]

Spoljašnje veze[уреди]

  • „5-HT2B. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.