5-hydroxytryptamine receptor 1B also known as the 5-HT1B receptor is a protein that in humans is encoded by the HTR1B gene.[1][2] The 5-HT1B receptor is a 5-HT receptor subtype.[3]
Contents
Tissue distribution and function[edit]
5-HT1B receptors are widely distributed throughout the CNS with the highest concentrations found in the frontal cortex, basal ganglia, striatum, and the hippocampus.[4] The function of the 5-HT1B receptor differs depending upon its location. In the frontal cortex, it is believed to act as a postsynaptic receptor inhibiting the release of dopamine. In the basal ganglia and the striatum, evidence suggests 5-HT signaling acts on an autoreceptor, inhibiting the release of serotonin[5] and decreasing glutamatergic transmission by reducing miniature excitatory postsynaptic potential (mEPSP) frequency,[6] respectively. In the hippocampus, a recent study has demonstrated that activation of postsynaptic 5-HT1B heteroreceptors produces a facilitation in excitatory synaptic transmission which is altered in depression.[7] When the expression of 5-HT1B in human cortex was traced throughout life, significant changes during adolescence were observed, in a way that is strongly correlated with the expression of 5-HT1E.[8]
Outside the brain, 5-HT1B receptor activation also has vascular effects, such as pulmonary vasoconstriction. Furthermore, blocking 5-HT1B receptor signaling decreases the number of osteoblasts, bone mass, and the bone formation rate.[9]
Knockout mice lacking the 5-HT1B gene have shown an increase in aggression and a higher preference for alcohol.[10] Under basal conditions, knockout mice present with a "normal" phenotype and exhibit a sucrose preference (lack of sucrose preference is considered a measure of anhedonia). However, after undergoing chronic unpredictable stress treatment to induce a "depression-like" phenotype these animals do not benefit from administration of selective serotonin reuptake inhibitor (SSRIs).[7]
Ligands[edit]
Agonists[edit]
- ergotamine (vasoconstrictor in migraine)
- Oxymetazoline
- sumatriptan (vasoconstrictor in migraine)
- zolmitriptan
- 5-Carboxamidotryptamine
- CGS-12066A
- CP-93,129 (peripherally acting)
- CP-94,253
- CP-122,288 (mixed 5-HT1B/1D agonist)
- CP-135,807 (mixed 5-HT1B/1D agonist)
- RU-24969 (mixed 5-HT1A/1B agonist)
Partial agonists[edit]
Antagonists and inverse agonists[edit]
- methiothepin (antipsychotic)
- yohimbine (aphrodisiac)
- metergoline
- Aripiprazole
- isamoltane
- AR-A000002[11]
- SB-216,641
- SB-224,289 (inverse agonist)[12]
- SB-236,057 (inverse agonist)[13]
Genetics[edit]
In humans the protein is coded by the gene HTR1B.
A genetic variant in the promotor region, A-161T, has been examined with respect to personality traits and showed no major effect.[14]
See also[edit]
References[edit]
- ^ Jin H, Oksenberg D, Ashkenazi A, Peroutka SJ, Duncan AM, Rozmahel R, Yang Y, Mengod G, Palacios JM, O'Dowd BF (March 1992). "Characterization of the human 5-hydroxytryptamine1B receptor". J. Biol. Chem. 267 (9): 5735–8. PMID 1348246.
- ^ Sanders AR, Cao Q, Taylor J, Levin TE, Badner JA, Cravchik A, Comeron JM, Naruya S, Del Rosario A, Salvi DA, Walczyk KA, Mowry BJ, Levinson DF, Crowe RR, Silverman JM, Gejman PV (February 2001). "Genetic diversity of the human serotonin receptor 1B (HTR1B) gene". Genomics 72 (1): 1–14. doi:10.1006/geno.2000.6411. PMID 11247661.
- ^ "Entrez Gene: HTR1B 5-hydroxytryptamine (serotonin) receptor 1B".
- ^ "5-hydroxytryptamine (serotonin) receptor 1B, G protein-coupled". Retrieved 23 Feb 2013.
- ^ Pytliak M, Vargová V, Mechírová V, Felšöci M (2011). "Serotonin receptors - from molecular biology to clinical applications". Physiol Res 60 (1): 15–25. PMID 20945968.
- ^ Huang CC, Yeh CM, Wu MY, Hsu KS (2013). "A single in vivo cocaine administration impairs 5-HT1B receptor-induced long-term depression in the nucleus accumbens". J. Neurochem. 125 (6): 809–21. doi:10.1111/jnc.12227. PMID 23452061.
- ^ a b Cai X, Kallarackal AJ, Kvarta MD, Goluskin S, Gaylor K, Bailey AM, Lee HK, Huganir RL, Thompson SM (2013). "Local potentiation of excitatory synapses by serotonin and its alteration in rodent models of depression". Nat. Neurosci. 16 (4): 464–72. doi:10.1038/nn.3355. PMID 23502536.
- ^ Shoval, G., Bar-Shira O., Zalsman G., John J. Mann and Chechik G. (2014) Transitions in the transcriptome of the serotonergic and dopaminergic systems in the human brain during adolescence. European Neuropsychopharmacology. (2014). "Transitions in the transcriptome of the serotonergic and dopaminergic systems in the human brain during adolescence". European neuropsychopharmacology 24 (7): 1123–32. doi:10.1016/j.euroneuro.2014.02.009. PMID 24721318.
- ^ Yadav VK, Ryu JH, Suda N, Tanaka KF, Gingrich JA, Schütz G, Glorieux FH, Chiang CY, Zajac JD, Insogna KL, Mann JJ, Hen R, Ducy P, Karsenty G (November 2008). "Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum". Cell 135 (5): 825–37. doi:10.1016/j.cell.2008.09.059. PMC 2614332. PMID 19041748.
- ^ Hoyer D, Hannon JP, Martin GR (2002). "Molecular, pharmacological and functional diversity of 5-HT receptors". Pharmacol. Biochem. Behav. 71 (4): 533–54. doi:10.1016/S0091-3057(01)00746-8. PMID 11888546.
- ^ Hudzik, TJ; Yanek, M; Porrey, T; Evenden, J; Paronis, C; Mastrangelo, M; Ryan, C; Ross, S; Stenfors, C (2003). "Behavioral pharmacology of AR-A000002, a novel, selective 5-hydroxytryptamine(1B) antagonist.". The Journal of Pharmacology and Experimental Therapeutics 304 (3): 1072–84. doi:10.1124/jpet.102.045468. PMID 12604684.
- ^ Selkirk, JV; Scott, C; Ho, M; Burton, MJ; Watson, J; Gaster, LM; Collin, L; Jones, BJ; Middlemiss, DN; Price, GW (1998). "SB-224289--a novel selective (human) 5-HT1B receptor antagonist with negative intrinsic activity.". British Journal of Pharmacology 125 (1): 202–8. doi:10.1038/sj.bjp.0702059. PMC 1565605. PMID 9776361.
- ^ Roberts, C; Watson, J; Price, GW; Middlemiss, DN (2001). "SB-236057-A: a selective 5-HT1B receptor inverse agonist.". CNS Drug Reviews 7 (4): 433–44. doi:10.1111/j.1527-3458.2001.tb00209.x. PMID 11830759.
- ^ Tsai SJ, Wang YC, Chen JY, Hong CJ (2003). "Allelic variants of the tryptophan hydroxylase (A218C) and serotonin 1B receptor (A-161T) and personality traits". Neuropsychobiology 48 (2): 68–71. doi:10.1159/000072879. PMID 14504413.
External links[edit]
- "5-HT1B". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
Further reading[edit]
- Olivier B, van Oorschot R (2006). "5-HT1B receptors and aggression: a review.". Eur. J. Pharmacol. 526 (1–3): 207–17. doi:10.1016/j.ejphar.2005.09.066. PMID 16310769.
- Hamblin MW, Metcalf MA, McGuffin RW, Karpells S (1992). "Molecular cloning and functional characterization of a human 5-HT1B serotonin receptor: a homologue of the rat 5-HT1B receptor with 5-HT1D-like pharmacological specificity". Biochem. Biophys. Res. Commun. 184 (2): 752–9. doi:10.1016/0006-291X(92)90654-4. PMID 1315531.
- Veldman SA, Bienkowski MJ (1992). "Cloning and pharmacological characterization of a novel human 5-hydroxytryptamine1D receptor subtype". Mol. Pharmacol. 42 (3): 439–44. PMID 1328844.
- Demchyshyn L, Sunahara RK, Miller K et al. (1992). "A human serotonin 1D receptor variant (5HT1D beta) encoded by an intronless gene on chromosome 6". Proc. Natl. Acad. Sci. U.S.A. 89 (12): 5522–6. doi:10.1073/pnas.89.12.5522. PMC 49324. PMID 1351684.
- Levy FO, Gudermann T, Perez-Reyes E et al. (1992). "Molecular cloning of a human serotonin receptor (S12) with a pharmacological profile resembling that of the 5-HT1D subtype". J. Biol. Chem. 267 (11): 7553–62. PMID 1559993.
- Weinshank RL, Zgombick JM, Macchi MJ et al. (1992). "Human serotonin 1D receptor is encoded by a subfamily of two distinct genes: 5-HT1D alpha and 5-HT1D beta". Proc. Natl. Acad. Sci. U.S.A. 89 (8): 3630–4. doi:10.1073/pnas.89.8.3630. PMC 48922. PMID 1565658.
- Mochizuki D, Yuyama Y, Tsujita R et al. (1992). "Cloning and expression of the human 5-HT1B-type receptor gene". Biochem. Biophys. Res. Commun. 185 (2): 517–23. doi:10.1016/0006-291X(92)91655-A. PMID 1610347.
- Nöthen MM, Erdmann J, Shimron-Abarbanell D, Propping P (1995). "Identification of genetic variation in the human serotonin 1D beta receptor gene". Biochem. Biophys. Res. Commun. 205 (2): 1194–200. doi:10.1006/bbrc.1994.2792. PMID 7802650.
- Ng GY, George SR, Zastawny RL et al. (1993). "Human serotonin1B receptor expression in Sf9 cells: phosphorylation, palmitoylation, and adenylyl cyclase inhibition". Biochemistry 32 (43): 11727–33. doi:10.1021/bi00094a032. PMID 8218242.
- Bouchelet I, Cohen Z, Case B et al. (1996). "Differential expression of sumatriptan-sensitive 5-hydroxytryptamine receptors in human trigeminal ganglia and cerebral blood vessels". Mol. Pharmacol. 50 (2): 219–23. PMID 8700126.
- Varnäs K, Hall H, Bonaventure P, Sedvall G (2001). "Autoradiographic mapping of 5-HT(1B) and 5-HT(1D) receptors in the post mortem human brain using [(3)H]GR 125743". Brain Res. 915 (1): 47–57. doi:10.1016/S0006-8993(01)02823-2. PMID 11578619.
- Salim K, Fenton T, Bacha J et al. (2002). "Oligomerization of G-protein-coupled receptors shown by selective co-immunoprecipitation". J. Biol. Chem. 277 (18): 15482–5. doi:10.1074/jbc.M201539200. PMID 11854302.
- Hasegawa Y, Higuchi S, Matsushita S, Miyaoka H (2002). "Association of a polymorphism of the serotonin 1B receptor gene and alcohol dependence with inactive aldehyde dehydrogenase-2". Journal of neural transmission (Vienna, Austria : 1996) 109 (4): 513–21. doi:10.1007/s007020200042. PMID 11956970.
- Hawi Z, Dring M, Kirley A et al. (2003). "Serotonergic system and attention deficit hyperactivity disorder (ADHD): a potential susceptibility locus at the 5-HT(1B) receptor gene in 273 nuclear families from a multi-centre sample". Mol. Psychiatry 7 (7): 718–25. doi:10.1038/sj.mp.4001048. PMID 12192616.
- Mammalian Gene Collection Program Team; Strausberg, R. L.; Feingold, E. A.; Grouse, L. H. et al. (2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proceedings of the National Academy of Sciences 99 (26): 16899–16903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Huang YY, Oquendo MA, Friedman JM et al. (2003). "Substance abuse disorder and major depression are associated with the human 5-HT1B receptor gene (HTR1B) G861C polymorphism". Neuropsychopharmacology 28 (1): 163–9. doi:10.1038/sj.npp.1300000. PMID 12496953.
- Quist JF, Barr CL, Schachar R et al. (2003). "The serotonin 5-HT1B receptor gene and attention deficit hyperactivity disorder". Mol. Psychiatry 8 (1): 98–102. doi:10.1038/sj.mp.4001244. PMID 12556913.
- Sinha R, Cloninger CR, Parsian A (2003). "Linkage disequilibrium and haplotype analysis between serotonin receptor 1B gene variations and subtypes of alcoholism". Am. J. Med. Genet. B Neuropsychiatr. Genet. 121 (1): 83–8. doi:10.1002/ajmg.b.20064. PMID 12898580.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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