5-HT1B receptor

5-hydroxytryptamine receptor 1B also known as the 5-HT1B receptor is a protein that in humans is encoded by the HTR1B gene.[5][6] The 5-HT1B receptor is a 5-HT receptor subtype.[7]

HTR1B
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesHTR1B, 5-HT1B, 5-HT1DB, HTR1D2, HTR1DB, S12, 5-HT-1B, 5-HT-1D-beta, 5-hydroxytryptamine receptor 1B
External IDsOMIM: 182131 MGI: 96274 HomoloGene: 669 GeneCards: HTR1B
Orthologs
SpeciesHumanMouse
Entrez

3351

15551

Ensembl

ENSG00000135312

ENSMUSG00000049511

UniProt

P28222

P28334

RefSeq (mRNA)

NM_000863

NM_010482

RefSeq (protein)

NP_000854

NP_034612

Location (UCSC)Chr 6: 77.46 – 77.46 MbChr 9: 81.51 – 81.52 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Tissue distribution and function

5-HT1B receptors are widely distributed throughout the central nervous system with the highest concentrations found in the frontal cortex, basal ganglia, striatum, and the hippocampus.[8] 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[9] and decreasing glutamatergic transmission by reducing miniature excitatory postsynaptic potential (mEPSP) frequency,[10] 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.[11] 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.[12]

Outside of the CNS, the 5-HT1B receptor is also expressed on the endothelium of blood vessels, particularly in the meninges.[13] Activation of these receptors results in vasoconstriction. The high distribution of vasoconstrictive 5-HT1B and 5-HT1D receptors around the brain makes them a valuable drug target for the treatment of migraines.[13]

Blocking 5-HT1B receptor signalling also increases the number of osteoblasts, bone mass, and the bone formation rate.[14]

Knockout mice lacking the 5-HT1B gene have been reported to have a higher preference for alcohol, although later studies failed to replicate such abnormalities in alcohol consumption.[15] These mice have also been reported to have a lower measure of anxiety (such as on the elevated plus maze test) and a higher measure of aggression.[15]

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).[11]

Ligands

Agonists

Partial agonists

Antagonists and inverse agonists

Undetermined Action

Genetics

In humans the protein is coded by the gene HTR1B.

A genetic variant in the promoter region, A-161T, has been examined with respect to personality traits and showed no major effect.[20]

See also

References
  1. GRCh38: Ensembl release 89: ENSG00000135312 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000049511 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Jin H, Oksenberg D, Ashkenazi A, Peroutka SJ, Duncan AM, Rozmahel R, Yang Y, Mengod G, Palacios JM, O'Dowd BF (Mar 1992). "Characterization of the human 5-hydroxytryptamine1B receptor". The Journal of Biological Chemistry. 267 (9): 5735–8. doi:10.1016/S0021-9258(18)42612-9. PMID 1348246.
  6. 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 (Feb 2001). "Genetic diversity of the human serotonin receptor 1B (HTR1B) gene". Genomics. 72 (1): 1–14. doi:10.1006/geno.2000.6411. PMID 11247661.
  7. "Entrez Gene: HTR1B 5-hydroxytryptamine (serotonin) receptor 1B".
  8. "5-hydroxytryptamine (serotonin) receptor 1B, G protein-coupled". Retrieved 23 Feb 2013.
  9. Pytliak M, Vargová V, Mechírová V, Felšöci M (2011). "Serotonin receptors - from molecular biology to clinical applications". Physiological Research. 60 (1): 15–25. doi:10.33549/physiolres.931903. PMID 20945968.
  10. Huang CC, Yeh CM, Wu MY, Hsu KS (Jun 2013). "A single in vivo cocaine administration impairs 5-HT(1B) receptor-induced long-term depression in the nucleus accumbens". Journal of Neurochemistry. 125 (6): 809–21. doi:10.1111/jnc.12227. PMID 23452061. S2CID 45859780.
  11. Cai X, Kallarackal AJ, Kvarta MD, Goluskin S, Gaylor K, Bailey AM, Lee HK, Huganir RL, Thompson SM (Apr 2013). "Local potentiation of excitatory synapses by serotonin and its alteration in rodent models of depression". Nature Neuroscience. 16 (4): 464–72. doi:10.1038/nn.3355. PMC 3609911. PMID 23502536.
  12. Shoval G, Bar-Shira O, Zalsman G, John Mann J, Chechik G (Jul 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. S2CID 14534307.
  13. Tepper, S. J.; Rapoport, A. M.; Sheftell, F. D. (2002). "Mechanisms of action of the 5-HT1B/1D receptor agonists". Archives of Neurology. 59 (7): 1084–1088. doi:10.1001/archneur.59.7.1084. PMID 12117355.
  14. 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 (Nov 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.
  15. Hoyer D, Hannon JP, Martin GR (Apr 2002). "Molecular, pharmacological and functional diversity of 5-HT receptors". Pharmacology Biochemistry and Behavior. 71 (4): 533–54. doi:10.1016/S0091-3057(01)00746-8. PMID 11888546. S2CID 25543069.
  16. Hudzik TJ, Yanek M, Porrey T, Evenden J, Paronis C, Mastrangelo M, Ryan C, Ross S, Stenfors C (Mar 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. S2CID 20463714.
  17. Selkirk JV, Scott C, Ho M, Burton MJ, Watson J, Gaster LM, Collin L, Jones BJ, Middlemiss DN, Price GW (Sep 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.
  18. 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. PMC 6741665. PMID 11830759.
  19. Nguyen L, Thomas KL, Lucke-Wold BP, Cavendish JZ, Crowe MS, Matsumoto RR (2016). "Dextromethorphan: An update on its utility for neurological and neuropsychiatric disorders". Pharmacol. Ther. 159: 1–22. doi:10.1016/j.pharmthera.2016.01.016. PMID 26826604.
  20. 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. S2CID 42559772.

Further reading
  • "5-HT1B". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
  • Human HTR1B genome location and HTR1B gene details page in the UCSC Genome Browser.
  • Overview of all the structural information available in the PDB for UniProt: P28222 (5-hydroxytryptamine receptor 1B) at the PDBe-KB.

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