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5-HT1B receptor

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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; OMA:HTR1B - orthologs
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

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]

Tissue distribution and function

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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 terminal 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][failed verification]

Activation of the serotonin 5-HT1B receptor appears to mediate the prosocial effects of entactogens acting as serotonin releasing agents like MDMA in animals.[16][17][18][19] In addition, serotonin 5-HT1B receptor activation appears to mediate the locomotor hyperactivity of these agents.[20][21][22] The serotonin 5-HT1B receptor also appears to be required for the persisting antidepressant- and anxiolytic-like effects as well as acute hypolocomotion of the serotonergic psychedelic and non-selective serotonin receptor agonist psilocybin in animals.[23]

Ligands

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Agonists

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Partial agonists

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Antagonists and inverse agonists

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Unknown

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Genetics

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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.[28]

See also

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References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000135312 – Ensembl, May 2017
  2. ^ a b c 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, et al. (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, et al. (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. ^ a b Cai X, Kallarackal AJ, Kvarta MD, Goluskin S, Gaylor K, Bailey AM, et al. (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. ^ a b Tepper SJ, Rapoport AM, Sheftell FD (July 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, et al. (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. ^ a b 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. ^ Nichols DE (2022). "Entactogens: How the Name for a Novel Class of Psychoactive Agents Originated". Front Psychiatry. 13: 863088. doi:10.3389/fpsyt.2022.863088. PMC 8990025. PMID 35401275.
  17. ^ Rein B, Raymond K, Boustani C, Tuy S, Zhang J, St Laurent R, et al. (April 2024). "MDMA enhances empathy-like behaviors in mice via 5-HT release in the nucleus accumbens". Sci Adv. 10 (17): eadl6554. Bibcode:2024SciA...10L6554R. doi:10.1126/sciadv.adl6554. PMC 11042730. PMID 38657057.
  18. ^ Heifets BD, Salgado JS, Taylor MD, Hoerbelt P, Cardozo Pinto DF, Steinberg EE, et al. (December 2019). "Distinct neural mechanisms for the prosocial and rewarding properties of MDMA". Sci Transl Med. 11 (522). doi:10.1126/scitranslmed.aaw6435. PMC 7123941. PMID 31826983.
  19. ^ Walsh JJ, Llorach P, Cardozo Pinto DF, Wenderski W, Christoffel DJ, Salgado JS, et al. (October 2021). "Systemic enhancement of serotonin signaling reverses social deficits in multiple mouse models for ASD". Neuropsychopharmacology. 46 (11): 2000–2010. doi:10.1038/s41386-021-01091-6. PMC 8429585. PMID 34239048.
  20. ^ Martinez-Price D, Krebs-Thomson K, Geyer M (1 January 2002). "Behavioral Psychopharmacology of MDMA and MDMA-Like Drugs: A Review of Human and Animal Studies". Addiction Research & Theory. 10 (1). Informa UK Limited: 43–67. doi:10.1080/16066350290001704. ISSN 1606-6359.
  21. ^ Rempel NL, Callaway CW, Geyer MA (May 1993). "Serotonin1B receptor activation mimics behavioral effects of presynaptic serotonin release". Neuropsychopharmacology. 8 (3): 201–211. doi:10.1038/npp.1993.22. PMID 8099482.
  22. ^ Scearce-Levie K, Viswanathan SS, Hen R (January 1999). "Locomotor response to MDMA is attenuated in knockout mice lacking the 5-HT1B receptor". Psychopharmacology (Berl). 141 (2): 154–161. doi:10.1007/s002130050819. PMID 9952039.
  23. ^ Fleury S, Nautiyal K (December 2024). "ACNP 63rd Annual Meeting: Poster Abstracts P609-P914: P691. The Non-Hallucinogenic Serotonin 1B Receptor is Necessary for the Persisting Behavioral Effects of Psilocybin in Mice". Neuropsychopharmacology. 49 (Suppl 1): 418–594 (466). doi:10.1038/s41386-024-02013-y. PMID 39643635.
  24. ^ Hudzik TJ, Yanek M, Porrey T, Evenden J, Paronis C, Mastrangelo M, et al. (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.
  25. ^ Selkirk JV, Scott C, Ho M, Burton MJ, Watson J, Gaster LM, et al. (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.
  26. ^ 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.
  27. ^ 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.
  28. ^ 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

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  • "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.

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

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