5-HT1B receptor
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| Location (UCSC) | Chr 6: 77.46 – 77.46 Mb | Chr 9: 81.51 – 81.52 Mb | |||||||
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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
5-HT1B receptors are widely distributed throughout the
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]
Ligands
Agonists
- 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
Antagonists and inverse agonists
- Methiothepin (antipsychotic)
- Yohimbine (aphrodisiac)
- Metergoline
- Aripiprazole
- Isamoltane
- AR-A000002[16]
- SB-216,641
- SB-224,289 (inverse agonist)[17]
- SB-236,057 (inverse agonist)[18]
Undetermined Action
- Cough Suppressant)[19]
Genetics
In humans the protein is coded by the gene HTR1B.
A genetic variant in the promoter region, personality traits and showed no major effect.[20]
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000135312 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000049511 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 1348246.
- PMID 11247661.
- ^ "Entrez Gene: HTR1B 5-hydroxytryptamine (serotonin) receptor 1B".
- ^ "5-hydroxytryptamine (serotonin) receptor 1B, G protein-coupled". Retrieved 23 Feb 2013.
- PMID 20945968.
- S2CID 45859780.
- ^ PMID 23502536.
- S2CID 14534307.
- ^ PMID 12117355.
- PMID 19041748.
- Lay summary in: Michael Smith. "Serotonin in Gut Linked to Bone Formation". Medpage Today. Archived from the original on 2016-03-03.
- ^ S2CID 25543069.
- S2CID 20463714.
- PMID 9776361.
- PMID 11830759.
- PMID 26826604.
- 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. 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. 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, Seeman P, Van Tol HH, Niznik HB (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. 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. 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. 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. 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. PMID 7802650.
- Ng GY, George SR, Zastawny RL, Caron M, Bouvier M, Dennis M, O'Dowd BF (Nov 1993). "Human serotonin1B receptor expression in Sf9 cells: phosphorylation, palmitoylation, and adenylyl cyclase inhibition". Biochemistry. 32 (43): 11727–33. 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 [(3)H]GR 125743". Brain Research. 915 (1): 47–57. S2CID 43104381.
- Salim K, Fenton T, Bacha J, Urien-Rodriguez H, Bonnert T, Skynner HA, Watts E, Kerby J, Heald A, Beer M, McAllister G, Guest PC (May 2002). "Oligomerization of G-protein-coupled receptors shown by selective co-immunoprecipitation". The Journal of Biological Chemistry. 277 (18): 15482–5. 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. S2CID 35750034.
- Hawi Z, Dring M, Kirley A, Foley D, Kent L, Craddock N, Asherson P, Curran S, Gould A, Richards S, Lawson D, Pay H, Turic D, Langley K, Owen M, O'Donovan M, Thapar A, Fitzgerald M, Gill M (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. PMID 12192616.
- Huang YY, Oquendo MA, Friedman JM, Greenhill LL, Brodsky B, Malone KM, Khait V, Mann JJ (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. PMID 12496953.
- Quist JF, Barr CL, Schachar R, Roberts W, Malone M, Tannock R, Basile VS, Beitchman J, Kennedy JL (Jan 2003). "The serotonin 5-HT1B receptor gene and attention deficit hyperactivity disorder". Molecular Psychiatry. 8 (1): 98–102. 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. S2CID 33460360.
External links
- "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.