5-HT2B receptor: Difference between revisions
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==References== |
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* {{cite web | url = http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2322 | title = 5-HT<sub>2B</sub> | accessdate = | author = | authorlink = | coauthors = | date = | format = | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology | pages = | language = | archiveurl = | archivedate = | quote = }} |
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==Further reading== |
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Revision as of 11:04, 25 November 2008
Template:PBB 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 hallucinogenic effects of phenylisopropylamine hallucinogens.[1]
The 5-HT2B receptor subtype is involved in:
- CNS: presynaptic inhibition, behavioural effects[3]
- Vascular: pulmonary vasoconstriction[4]
- Cardiac: stimulates proliferation of cardiac fibroblasts,[5][6] which with chronic overstimulation of 5-HT2B can lead to a valvopathy known as cardiac fibrosis.
- 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,[7] and with the abnormal acute serotonin release produced by drugs such as MDMA.[8]
Ligands
As of 2008, 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. Several overviews of current work in the field have been published.[9][10]
Agonists
- Selective
- BW-723C86:[11] fair functional subtype selectivity; almost full agonist. Anxiolytic in vivo.[12]
- Ro 60-0175:[11] functionally selective over 5-HT2A, moderately over 5-HT2C; almost full agonist
- Non-selective
Antagonists
- Sarpogrelate (mixed 5-HT2A / 5-HT2B antagonist)
- Lisuride (primarily dopamine agonist, but 5-HT2B antagonist effects as well)[14]
- RS-127,445:[15] high affinity; subtype selective (1000x), selective over at least eight other 5-HTR types; orally bioavailable.
- EGIS-7625: reasonable selectivity over both 5-HT2A and 5-HT2C
- SB-200,646
- SB-204,741 (N-(1-Methyl-1H-indolyl-5-yl)-N-(3-methyl-5-isothiazolyl)urea)
- SB-206,553 (mixed 5-HT2B / 5-HT2C antagonist)
- SB-215,505 (6-chloro-5-methyl-1-(5-quinolylcarbamoyl)indoline)
- SB-228,357
- LY-272,015
See also
References
- ^ a b "Entrez Gene: HTR2B 5-hydroxytryptamine (serotonin) receptor 2B".
- ^ 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.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ 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. doi:10.1523/JNEUROSCI.5723-07.2008. PMID 18337424.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ 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. doi:10.1038/nm764. PMID 12244304.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Elangbam CS, Job LE, Zadrozny LM, Barton JC, Yoon LW, Gates LD, Slocum N. 5-hydroxytryptamine (5HT)-induced valvulopathy: compositional valvular alterations are associated with 5HT2B receptor and 5HT transporter transcript changes in Sprague-Dawley rats. Experimental and Toxicologic Pathology. 2008 Aug;60(4-5):253-62. PMID 18511249
- ^ Monassier L, Laplante MA, Jaffré F, Bousquet P, Maroteaux L, de Champlain J. Serotonin 5-HT(2B) receptor blockade prevents reactive oxygen species-induced cardiac hypertrophy in mice. Hypertension. 2008 Aug;52(2):301-7. PMID 18591460
- ^ Callebert J, Esteve JM, Hervé P, Peoc'h K, Tournois C, Drouet L, Launay JM, Maroteaux L. Evidence for a control of plasma serotonin levels by 5-hydroxytryptamine(2B) receptors in mice. Journal of Pharmacology and Experimental Therapeutics. 2006 May;317(2):724-31. PMID 16461587
- ^ Doly S, Valjent E, Setola V, Callebert J, Hervé D, Launay JM, Maroteaux L. Serotonin 5-HT2B receptors are required for 3,4-methylenedioxymethamphetamine-induced hyperlocomotion and 5-HT release in vivo and in vitro. Journal of Neuroscience. 2008 Mar 12;28(11):2933-40. PMID 18337424
- ^ Poissonnet G, Parmentier JG, Boutin JA, Goldstein S. The emergence of selective 5-HT 2B antagonists structures, activities and potential therapeutic applications. Mini Reviews in Medicinal Chemistry. 2004 Mar;4(3):325-30. PMID 15032678
- ^ 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.
{{cite journal}}:|pages=has extra text (help); Cite journal requires|journal=(help) - ^ a b c 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.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - ^ Kennett GA, Trail B, Bright F. Anxiolytic-like actions of BW 723C86 in the rat Vogel conflict test are 5-HT2B receptor mediated. Neuropharmacology. 1998 Dec;37(12):1603-10. PMID 9886683
- ^ 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.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - ^ Hofmann C, Penner U, Dorow R, Pertz HH, Jähnichen S, Horowski R, Latté KP, Palla D, Schurad B. 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. Clinical Neuropharmacology. 2006 Mar-Apr;29(2):80-6. PMID 16614540
- ^ 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.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link)
External links
- "5-HT2B". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
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Further reading
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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