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HTR1B
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4IAQ, 4IAR
Identifiers
Aliases	HTR1B, 5-HT1B, 5-HT1DB, HTR1D2, HTR1DB, S12, 5-HT-1B, 5-HT-1D-beta, 5-hydroxytryptamine receptor 1B
External IDs	OMIM: 182131; MGI: 96274; HomoloGene: 669; GeneCards: HTR1B; OMA:HTR1B - orthologs
Gene location (Human) Chr. Chromosome 6 (human) Band 6q14.1 Start 77,460,924 bp End 77,463,491 bp
Gene location (Mouse) Chr. Chromosome 9 (mouse) Band 9 E1|9 44.61 cM Start 81,510,344 bp End 81,515,881 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in popliteal artery tibial arteries right coronary artery Descending thoracic aorta left coronary artery ascending aorta stromal cell of endometrium prefrontal cortex nucleus accumbens caudate nucleus Top expressed in ventral nuclear group ventral posteromedial nucleus nucleus accumbens ascending aorta lumbar spinal ganglion dorsal nucleus of lateral geniculate body subthalamus ventral posterolateral nucleus paraventricular nucleus of thalamus ventral lateral nucleus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function G protein-coupled receptor activity signal transducer activity G protein-coupled serotonin receptor activity protein binding neurotransmitter receptor activity serotonin binding voltage-gated calcium channel activity involved in regulation of presynaptic cytosolic calcium levels Cellular component cytoplasm integral component of membrane membrane integral component of plasma membrane plasma membrane calyx of Held integral component of presynaptic membrane serotonergic synapse dendrite Biological process chemical synaptic transmission G protein-coupled receptor internalization regulation of dopamine secretion regulation of behavior response to mineralocorticoid vasoconstriction adenylate cyclase-inhibiting serotonin receptor signaling pathway G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger cellular response to alkaloid negative regulation of serotonin secretion cellular response to temperature stimulus negative regulation of synaptic transmission, GABAergic protein kinase C-activating G protein-coupled receptor signaling pathway drinking behavior bone remodeling feeding behavior response to ethanol negative regulation of synaptic transmission, glutamatergic signal transduction response to cocaine positive regulation of vascular associated smooth muscle cell proliferation G protein-coupled receptor signaling pathway adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway animal behavior presynaptic modulation of chemical synaptic transmission regulation of synaptic vesicle exocytosis regulation of presynaptic cytosolic calcium ion concentration Sources:Amigo / QuickGO
Orthologs Species Human Mouse 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 Mb Chr 9: 81.51 – 81.52 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

5-hydroxytryptamine receptor 1B also known as the 5-HT_1B receptor is a protein that in humans is encoded by the HTR1B gene. The 5-HT_1B receptor is a 5-HT receptor subtype.

Tissue distribution and function

5-HT_1B receptors are widely distributed throughout the central nervous system with the highest concentrations found in the frontal cortex, basal ganglia, striatum, and the hippocampus. The function of the 5-HT_1B 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 and decreasing glutamatergic transmission by reducing miniature excitatory postsynaptic potential (mEPSP) frequency, respectively. In the hippocampus, a recent study has demonstrated that activation of postsynaptic 5-HT_1B heteroreceptors produces a facilitation in excitatory synaptic transmission which is altered in depression. When the expression of 5-HT_1B 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-HT_1E.

Outside of the CNS, the 5-HT_1B receptor is also expressed on the endothelium of blood vessels, particularly in the meninges. Activation of these receptors results in vasoconstriction. The high distribution of vasoconstrictive 5-HT_1B and 5-HT_1D receptors around the brain makes them a valuable drug target for the treatment of migraines.

Blocking 5-HT_1B receptor signalling also increases the number of osteoblasts, bone mass, and the bone formation rate.

Knockout mice lacking the 5-HT_1B gene have been reported to have a higher preference for alcohol, although later studies failed to replicate such abnormalities in alcohol consumption. 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.

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).

Activation of the serotonin 5-HT_1B receptor appears to mediate the prosocial effects of entactogens acting as serotonin releasing agents like MDMA in animals. In addition, serotonin 5-HT_1B receptor activation appears to mediate the locomotor hyperactivity of these agents. The serotonin 5-HT_1B 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.

Ligands

Agonists

• 5-Carboxamidotryptamine (5-CT)
• Almotriptan
• Anpirtoline (D-16949)
• Avitriptan
• Batoprazine
• CGS-12066A
• CP-93,129 (peripherally acting)
• CP-94,253
• CP-122,288 (mixed 5-HT_1B/1D agonist)
• CP-135,807 (mixed 5-HT_1B/1D agonist)
• Dihydroergotamine
• Donitriptan
• Eletriptan
• Eltoprazine (DU-28853)
• Ergotamine
• Fluprazine
• Frovatriptan
• L-741,604
• Lisuride
• mCPP
• Methylergometrine (methylergonovine)
• Methysergide
• Naratriptan
• Oxymetazoline
• Pergolide
• Rizatriptan
• RU-24969 (mixed 5-HT_1A/1B agonist)
• Serotonin
• Sumatriptan
• TFMPP
• Tryptamine psychedelics (e.g., 5-MeO-DMT, DPT, psilocin/psilocybin)
• Zolmitriptan

Partial agonists

• Asenapine
• AZ10419369
• Bromocriptine
• Metergoline
• Naphthylpiperazine
• Vortioxetine
• Ziprasidone

Antagonists and inverse agonists

• Alprenolol
• AOP-208 (LB-208)
• AR-A000002 (AZD-8129)
• Aripiprazole
• AZD-1134
• AZD-3783
• AZ12320927
• Carteolol
• Elzasonan
• GR-55562
• GR-127935
• Isamoltane (CGP-361A)
• LY-393558
• Metitepine (methiothepin)
• NAS-181 (MCOMM)
• Oxprenolol
• Penbutolol
• Propranolol
• Risperidone
• SB-216,641
• SB-224,289 (inverse agonist)
• SB-236,057 (inverse agonist)
• SB-245,570
• SB-649,915
• Tertatolol
• Yohimbine

Unknown

• Dextromethorphan

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.

See also

• 5-HT₁ receptor
• 5-HT receptor

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, 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. ^ 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. ^ 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.
    • Lay summary in: Michael Smith. "Serotonin in Gut Linked to Bone Formation". Medpage Today. Archived from the original on 2016-03-03.
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. 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

• Olivier B, van Oorschot R (Dec 2005). "5-HT1B receptors and aggression: a review". European Journal of Pharmacology. 526 (1–3): 207–17. doi:10.1016/j.ejphar.2005.09.066. PMID 16310769.
• Hamblin MW, Metcalf MA, McGuffin RW, Karpells S (Apr 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". Biochemical and Biophysical Research Communications. 184 (2): 752–9. doi:10.1016/0006-291X(92)90654-4. PMID 1315531.
• Veldman SA, Bienkowski MJ (Sep 1992). "Cloning and pharmacological characterization of a novel human 5-hydroxytryptamine1D receptor subtype". Molecular Pharmacology. 42 (3): 439–44. PMID 1328844.
• Demchyshyn L, Sunahara RK, Miller K, Teitler M, Hoffman BJ, Kennedy JL, et al. (Jun 1992). "A human serotonin 1D receptor variant (5HT1D beta) encoded by an intronless gene on chromosome 6". Proceedings of the National Academy of Sciences of the United States of America. 89 (12): 5522–6. Bibcode:1992PNAS...89.5522D. doi:10.1073/pnas.89.12.5522. PMC 49324. PMID 1351684.
• Levy FO, Gudermann T, Perez-Reyes E, Birnbaumer M, Kaumann AJ, Birnbaumer L (Apr 1992). "Molecular cloning of a human serotonin receptor (S12) with a pharmacological profile resembling that of the 5-HT1D subtype". The Journal of Biological Chemistry. 267 (11): 7553–62. doi:10.1016/S0021-9258(18)42552-5. PMID 1559993.
• Weinshank RL, Zgombick JM, Macchi MJ, Branchek TA, Hartig PR (Apr 1992). "Human serotonin 1D receptor is encoded by a subfamily of two distinct genes: 5-HT1D alpha and 5-HT1D beta". Proceedings of the National Academy of Sciences of the United States of America. 89 (8): 3630–4. Bibcode:1992PNAS...89.3630W. doi:10.1073/pnas.89.8.3630. PMC 48922. PMID 1565658.
• Mochizuki D, Yuyama Y, Tsujita R, Komaki H, Sagai H (Jun 1992). "Cloning and expression of the human 5-HT1B-type receptor gene". Biochemical and Biophysical Research Communications. 185 (2): 517–23. doi:10.1016/0006-291X(92)91655-A. PMID 1610347.
• Nöthen MM, Erdmann J, Shimron-Abarbanell D, Propping P (Dec 1994). "Identification of genetic variation in the human serotonin 1D beta receptor gene". Biochemical and Biophysical Research Communications. 205 (2): 1194–200. doi:10.1006/bbrc.1994.2792. PMID 7802650.
• Ng GY, George SR, Zastawny RL, Caron M, Bouvier M, Dennis M, et al. (Nov 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, Séguéla P, Hamel E (Aug 1996). "Differential expression of sumatriptan-sensitive 5-hydroxytryptamine receptors in human trigeminal ganglia and cerebral blood vessels". Molecular Pharmacology. 50 (2): 219–23. PMID 8700126.
• Varnäs K, Hall H, Bonaventure P, Sedvall G (Oct 2001). "Autoradiographic mapping of 5-HT(1B) and 5-HT(1D) receptors in the post mortem human brain using GR 125743". Brain Research. 915 (1): 47–57. doi:10.1016/S0006-8993(01)02823-2. PMID 11578619. S2CID 43104381.
• Salim K, Fenton T, Bacha J, Urien-Rodriguez H, Bonnert T, Skynner HA, et al. (May 2002). "Oligomerization of G-protein-coupled receptors shown by selective co-immunoprecipitation". The Journal of Biological Chemistry. 277 (18): 15482–5. doi:10.1074/jbc.M201539200. PMID 11854302.
• Hasegawa Y, Higuchi S, Matsushita S, Miyaoka H (Apr 2002). "Association of a polymorphism of the serotonin 1B receptor gene and alcohol dependence with inactive aldehyde dehydrogenase-2". Journal of Neural Transmission. 109 (4): 513–21. doi:10.1007/s007020200042. PMID 11956970. S2CID 35750034.
• Hawi Z, Dring M, Kirley A, Foley D, Kent L, Craddock N, 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". Molecular Psychiatry. 7 (7): 718–25. doi:10.1038/sj.mp.4001048. PMID 12192616.
• Huang YY, Oquendo MA, Friedman JM, Greenhill LL, Brodsky B, Malone KM, et al. (Jan 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, Roberts W, Malone M, Tannock R, et al. (Jan 2003). "The serotonin 5-HT1B receptor gene and attention deficit hyperactivity disorder". Molecular Psychiatry. 8 (1): 98–102. doi:10.1038/sj.mp.4001244. PMID 12556913.
• Sinha R, Cloninger CR, Parsian A (Aug 2003). "Linkage disequilibrium and haplotype analysis between serotonin receptor 1B gene variations and subtypes of alcoholism". American Journal of Medical Genetics Part B. 121B (1): 83–8. doi:10.1002/ajmg.b.20064. PMID 12898580. S2CID 33460360.

External links

• "5-HT_1B". 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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