5-HT2B receptor

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5-hydroxytryptamine (serotonin) receptor 2B
Identifiers
SymbolsHTR2B; 5-HT(2B); 5-HT2B
External IDsOMIM601122 MGI109323 HomoloGene55492 IUPHAR: 5-HT2B GeneCards: HTR2B Gene
RNA expression pattern
250px
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez335715559
EnsemblENSG00000135914ENSMUSG00000026228
UniProtP41595Q7TNN4
RefSeq (mRNA)NM_000867NM_008311
RefSeq (protein)NP_000858NP_032337
Location (UCSC)Chr 2:
231.68 - 231.7 Mb
Chr 1:
87.93 - 87.94 Mb
PubMed search[1][2]

5-hydroxytryptamine (serotonin) receptor 2B, also known as HTR2B, is a 5-HT2 receptor, but also denotes the human gene encoding it.[1][2]

Function

The 5-HT2 receptors (of which the 5-HT2B receptor is a subtype) mediate many of the central and peripheral physiologic functions of serotonin. Cardiovascular effects include contraction of blood vessels and shape changes in platelets; central nervous system effects include neuronal sensitization to tactile stimuli and mediation of some of the effects of phenylisopropylamine hallucinogens.

The 5-HT2B receptor subtype is involved in:

  • CNS: presynaptic inhibition, behavioural effects[3]
  • Vascular: pulmonary vasoconstriction[4]
  • Cardiac: The 5-HT2B receptor regulates cardiac structure and functions as demonstrated by the abnormal cardiac development observed in 5-HT2B receptor null mice.[5] The 5-HT2B receptor stimulation can also lead to pathological proliferation of cardiac valves fibroblasts,[6] which with chronic overstimulation of 5-HT2B can lead to a severe valvulopathy. Moreover, 5-HT2B receptors were recently shown to be overexpressed in human failing heart and antagonists of 5-HT2B receptors were uncovered to prevent both angiotensin II or beta-adrenergic agonist-induced pathological cardiac hypertrophy in mouse.[7][8][9]
  • Serotonin transporter: 5-HT2B receptors regulate serotonin release via the serotonin transporter, and are important both to normal physiological regulation of serotonin levels in blood plasma,[10] and with the abnormal acute serotonin release produced by drugs such as MDMA.[3]

Ligands

As of 2009, few highly selective 5-HT2B receptor ligands have been discovered, although numerous potent non-selective compounds are known, particularly agents with concomitant 5-HT2C binding. Research in this area has been limited due to the cardiotoxicity of 5HT2B agonists, and the lack of clear therapeutic application for 5HT2B antagonists, but there is still a need for selective ligands for scientific research.[11]

Agonists

Selective
  • BW-723C86:[12] fair functional subtype selectivity; almost full agonist. Anxiolytic in vivo.[13]
  • Ro60-0175 [12] functionally selective over 5-HT2A, potent agonist at both 5-HT2B and 5-HT2C
  • VER-3323: selective for 5-HT2B/2C over 5-HT2A
  • α-Methyl-5-HT - moderately selective over 5-HT2A and 5-HT2C
Non-selective

Antagonists

Possible Applications

5-HT2B antagonists have previously been proposed as treatment for migraine headaches, and RS-127,445 was trialled in humans up to Phase I for this indication, but development was not continued.[23] More recent research has focused on possible application of 5-HT2B antagonists as treatments for chronic heart disease.[24][25]

See also

References

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External links

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

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.


  1. "Entrez Gene: HTR2B 5-hydroxytryptamine (serotonin) receptor 2B". 
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  11. Schuhmacher M (2007). "[Chiral arylmethoxytryptamines as 5-HT2B-receptor antagonists: synthesis, analysis and in-vitro pharmacology] (German)" (PDF). Ph.D. Dissertation. University of Regensburg: pages 6–17. Retrieved 2008-08-11. 
  12. 12.0 12.1 12.2 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 1571597Freely accessible. PMID 10498829. 
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  15. Ray TS; Manzoni, Olivier Jacques (2010). "Psychedelics and the human receptorome". PLoS ONE. 5 (2): e9019. doi:10.1371/journal.pone.0009019. PMC 2814854Freely accessible. PMID 20126400. 
  16. 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. 
  17. 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. 
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  19. 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 1566110Freely accessible. PMID 10455251. 
  20. 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. 
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