5-HT2B receptor

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5-hydroxytryptamine (serotonin) receptor 2B
Identifiers
Symbols	HTR2B; 5-HT(2B); 5-HT2B
External IDs	OMIM: 601122 MGI: 109323 HomoloGene: 55492 IUPHAR: 5-HT2B GeneCards: HTR2B Gene
Gene Ontology Molecular function • rhodopsin-like receptor activity • receptor activity • serotonin receptor activity Cellular component • integral to plasma membrane • membrane Biological process • signal transduction • G-protein signaling, coupled to IP3 second messenger (phospholipase C activating) • heart development • circulation • positive regulation of I-kappaB kinase/NF-kappaB cascade Sources: Amigo / EGO
RNA expression pattern
250px
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3357	15559
Ensembl	ENSG00000135914	ENSMUSG00000026228
UniProt	P41595	Q7TNN4
RefSeq (mRNA)	NM_000867	NM_008311
RefSeq (protein)	NP_000858	NP_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.

Function

The 5-HT₂ receptors (of which the 5-HT_2B 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-HT_2B receptor subtype is involved in:

• CNS: presynaptic inhibition, behavioural effects
• Vascular: pulmonary vasoconstriction
• Cardiac: The 5-HT_2B receptor regulates cardiac structure and functions as demonstrated by the abnormal cardiac development observed in 5-HT_2B receptor null mice. The 5-HT_2B receptor stimulation can also lead to pathological proliferation of cardiac valves fibroblasts, which with chronic overstimulation of 5-HT_2B can lead to a severe valvulopathy. Moreover, 5-HT_2B receptors were recently shown to be overexpressed in human failing heart and antagonists of 5-HT_2B receptors were uncovered to prevent both angiotensin II or beta-adrenergic agonist-induced pathological cardiac hypertrophy in mouse.

• Serotonin transporter: 5-HT_2B receptors regulate serotonin release via the serotonin transporter, and are important both to normal physiological regulation of serotonin levels in blood plasma, and with the abnormal acute serotonin release produced by drugs such as MDMA.

Ligands

As of 2009, few highly selective 5-HT_2B receptor ligands have been discovered, although numerous potent non-selective compounds are known, particularly agents with concomitant 5-HT_2C binding. Research in this area has been limited due to the cardiotoxicity of 5HT_2B agonists, and the lack of clear therapeutic application for 5HT_2B antagonists, but there is still a need for selective ligands for scientific research.

Agonists

Selective

• BW-723C86: fair functional subtype selectivity; almost full agonist. Anxiolytic in vivo.
• Ro60-0175 functionally selective over 5-HT_2A, potent agonist at both 5-HT_2B and 5-HT_2C
• VER-3323: selective for 5-HT_2B/2C over 5-HT_2A
• α-Methyl-5-HT - moderately selective over 5-HT_2A and 5-HT_2C

Non-selective

• MDMA (Ecstasy)
• MDA
• MEM
• Pergolide
• Cabergoline
• Norfenfluramine
• Chlorphentermine
• Aminorex
• mCPP
• Bromo-dragonfly
• Psilocin
• DMT
• 5-MeO-DMT

Antagonists

• Sarpogrelate (mixed 5-HT_2A / 5-HT_2B antagonist)
• Lisuride (primarily dopamine agonist, but 5-HT_2B antagonist effects as well)
• Tegaserod (primarily 5-HT₄ agonist, but also 5-HT_2B antagonist)
• RS-127,445: high affinity; subtype selective (1000x), selective over at least eight other 5-HTR types; orally bioavailable.
• SDZ SER-082: mixed 5-HT_2B/2C antagonist
• EGIS-7625: high selectivity over 5-HT_2A
• SB-200,646
• SB-204,741
• SB-206,553: mixed 5-HT_2B / 5-HT_2C antagonist and PAM at α7 nAChR
• SB-215,505
• SB-228,357
• LY-272,015

Possible Applications

5-HT_2B 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. More recent research has focused on possible application of 5-HT_2B antagonists as treatments for chronic heart disease.

See also

• 5-HT receptor

External links

• "5-HT_2B". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. 

Further reading

• 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. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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 Freely accessible. PMID 7582481. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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. CS1 maint: Multiple names: authors list (link)
• 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. CS1 maint: Multiple names: authors list (link)
• 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. CS1 maint: Multiple names: authors list (link)
• 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. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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 Freely accessible. PMID 11877320. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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 Freely accessible. PMID 12477932. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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. doi:10.1002/jcp.10287. PMID 12767050. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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 Freely accessible. PMID 15489334. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)

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