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Gene Review

HTR1B  -  5-hydroxytryptamine (serotonin) receptor...

Homo sapiens

Synonyms: 5-HT-1B, 5-HT-1D-beta, 5-HT1B, 5-HT1DB, 5-hydroxytryptamine receptor 1B, ...
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Disease relevance of HTR1B


Psychiatry related information on HTR1B


High impact information on HTR1B

  • Techniques to augment signaling by neurochemical mediators of leptin action that lie downstream of at least some levels of obesity-associated leptin resistance include activation of melanocortin receptors or 5-HT2C and 5-HT1B receptors [9].
  • In doing so, they advocate that the so-called '5-HT1-like' receptors, having been shown to be a heterogeneous population of 5-HT1B, 5-HT1D and 5-HT7 receptors, are now redundant [10].
  • We therefore investigated whether the 5-HT1B gene (HTR1B) is linked to alcoholism with aggressive and impulsive behavior in the human, as represented by 2 psychiatric diagnoses: antisocial personality disorder and intermittent explosive disorder comorbid with alcoholism [11].
  • Human 5-HT1A sites can be distinguished from human 5-HT1B, 5-HT2, and 5-HT3 sites and from equivalent sites in rat and bovine cortex [12].
  • Among these receptors, the 5-HT1B subtypes play a particular role as they are autoreceptors located on 5-HT neurons terminals and heteroreceptors located on non-serotonergic terminals where they control the release of the neurotransmitter [13].

Chemical compound and disease context of HTR1B


Biological context of HTR1B

  • Our results indicate that HTR1B is the target of substantial transcriptional genetic regulation by common haplotypes, which are in LD with the HTR1B single-nucleotide polymorphism (SNP) most commonly used in association studies [19].
  • Computational analysis of the HTR1B gene predicted that a 5' segment, spanning common DNA sequence variations, T-261G, A-161T, and -182INS/DEL-181, contained a putative functional promoter [19].
  • MS-RDA was shown to isolate DNA fragments that are hypermethylated and silenced, such as HTR1B, and those whose expressions are altered and the methylation statuses outside the promoter region are altered, such as EDN1 [1].
  • We systematically and comprehensively investigated polymorphisms of the HTR1B gene as well as their linkage disequilibrium and ancestral relationships [20].
  • Evidence for an association between the HTR1B gene and ADHD as a qualitative diagnosis, or the inattentive and hyperactive-impulsive quantitative traits was not supported by either TDT single marker analysis or haplotype analysis [5].

Anatomical context of HTR1B


Associations of HTR1B with chemical compounds


Physical interactions of HTR1B

  • We now report that Thr355Asn mutagenesis of the human 5-HT1D beta receptor alters the binding characteristics of the recombinant receptor in [3H]5-HT binding assays to a profile very similar to that of the rat 5-HT1B binding site [26].
  • The antagonist radioligand [3H]GR125743 and the agonist radioligand [3H]5-HT were used to investigate the pharmacological characteristics of the G protein uncoupled agonist low-affinity and G protein coupled agonist high-affinity conformations of the wild-type and mutant human 5-hydroxytryptamine 1B (5-HT1B) receptors [27].

Regulatory relationships of HTR1B

  • Accordingly, 5-hydroxytryptamine 1B receptor antagonists prevent G-proteinmediated inhibition of uptake in partially filled platelets and synaptic vesicles expressing VMAT2 [28].
  • We identified a haplotype block encompassing HTR1B and performed haplotype and single-marker association analyses for the eight SNPs within or flanking this block in 229 families of ADHD probands [29].
  • In acute migraine treatment, their mechanisms of action involve constricting the pain-producing intracranial extracerebral blood vessels at the 5-HT1B receptors and inhibiting the trigeminal neurotransmission at the peripheral and central 5-HT1D receptors [30].
  • A comparative study with a C6-glial/pcDNA3/5-HT1B cell line expressing a similar amount of cloned human 5-HT1B receptors (Bmax: 360 fmol/mg protein) showed almost no intrinsic agonist activity for metergoline, 1-naphtylpiperazine and GR 127,935 [31].
  • We have previously reported that the transfected Gi/Go protein-coupled human adenosine A1 receptor (expressed at 200 fmol/mg of protein) and the endogenous 5-HT1B receptor (not detectable using radioligand binding) suppress forskolin-stimulated cyclic AMP accumulation and stimulate increases in [Ca2+]i in Chinese hamster ovary cells (CHO) [32].

Other interactions of HTR1B

  • Silencing of HTR1B and reduced expression of EDN1 in human lung cancers, revealed by methylation-sensitive representational difference analysis [1].
  • In contrast, activation of 5-HT2A receptors with either 5-HT or (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane did not alter the 5-HT1B-like response [33].
  • The reduction of 5-HT1B-like responsiveness produced by 5-HT2C receptor activation was independent of protein kinase C activation and increases in the intracellular calcium concentration [33].
  • Similar studies on human cloned receptors confirmed that xanomeline is an agonist at human cloned 5-HT1A and 5-HT1B receptors [34].
  • Metergoline and the selective 5-HT 1B/D receptor ligands GR 127935 as well as GR 125743 showed significant intrinsic activity (43% to 69%) at the 5-HT 1D receptor subtype, whereas the nonselective ligand 1-naphthylpiperazine yielded less (15% to 19%) intrinsic activity at both receptor subtypes [35].

Analytical, diagnostic and therapeutic context of HTR1B


  1. Silencing of HTR1B and reduced expression of EDN1 in human lung cancers, revealed by methylation-sensitive representational difference analysis. Takai, D., Yagi, Y., Wakazono, K., Ohishi, N., Morita, Y., Sugimura, T., Ushijima, T. Oncogene (2001) [Pubmed]
  2. 5-hydroxytryptamine receptors in the human cardiovascular system. Kaumann, A.J., Levy, F.O. Pharmacol. Ther. (2006) [Pubmed]
  3. Functional reactivity of 5-HT receptors in human umbilical cord and maternal subcutaneous fat arteries after normotensive or pre-eclamptic pregnancy. Gupta, S., Hanff, L.M., Visser, W., Steegers, E.A., Saxena, P.R., Vulto, A.G., MaassenVanDenBrink, A. J. Hypertens. (2006) [Pubmed]
  4. Receptor specificity and trigemino-vascular inhibitory actions of a novel 5-HT1B/1D receptor partial agonist, 311C90 (zolmitriptan). Martin, G.R., Robertson, A.D., MacLennan, S.J., Prentice, D.J., Barrett, V.J., Buckingham, J., Honey, A.C., Giles, H., Moncada, S. Br. J. Pharmacol. (1997) [Pubmed]
  5. The serotonin receptor HTR1B: Gene polymorphisms in attention deficit hyperactivity disorder. Ickowicz, A., Feng, Y., Wigg, K., Quist, J., Pathare, T., Roberts, W., Malone, M., Schachar, R., Tannock, R., Kennedy, J.L., Barr, C.L. Am. J. Med. Genet. B Neuropsychiatr. Genet. (2007) [Pubmed]
  6. Serotonin 5-HT1A, 5-HT1B, and 5-HT2A receptor mRNA expression in subjects with major depression, bipolar disorder, and schizophrenia. López-Figueroa, A.L., Norton, C.S., López-Figueroa, M.O., Armellini-Dodel, D., Burke, S., Akil, H., López, J.F., Watson, S.J. Biol. Psychiatry (2004) [Pubmed]
  7. Substance abuse disorder and major depression are associated with the human 5-HT1B receptor gene (HTR1B) G861C polymorphism. Huang, Y.Y., Oquendo, M.A., Friedman, J.M., Greenhill, L.L., Brodsky, B., Malone, K.M., Khait, V., Mann, J.J. Neuropsychopharmacology (2003) [Pubmed]
  8. Association of 5-HT1B receptor gene and antisocial behavior in alcoholism. Soyka, M., Preuss, U.W., Koller, G., Zill, P., Bondy, B. Journal of neural transmission (Vienna, Austria : 1996) (2004) [Pubmed]
  9. Emerging therapeutic strategies for obesity. Foster-Schubert, K.E., Cummings, D.E. Endocr. Rev. (2006) [Pubmed]
  10. 5-HT1-like receptors: a time to bid goodbye. Saxena, P.R., De Vries, P., Villalón, C.M. Trends Pharmacol. Sci. (1998) [Pubmed]
  11. Linkage of antisocial alcoholism to the serotonin 5-HT1B receptor gene in 2 populations. Lappalainen, J., Long, J.C., Eggert, M., Ozaki, N., Robin, R.W., Brown, G.L., Naukkarinen, H., Virkkunen, M., Linnoila, M., Goldman, D. Arch. Gen. Psychiatry (1998) [Pubmed]
  12. Demonstration of inter- and intraspecies differences in serotonin binding sites by antibodies from an autistic child. Todd, R.D., Ciaranello, R.D. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  13. 5-HT-moduline controls serotonergic activity: implication in neuroimmune reciprocal regulation mechanisms. Grimaldi, B., Fillion, G. Prog. Neurobiol. (2000) [Pubmed]
  14. Site-selective serotonin agonists as discriminative stimuli. Glennon, R.A. Psychopharmacology series. (1988) [Pubmed]
  15. Hemodynamic and coronary effects of intravenous eletriptan, a 5HT1B/1D-receptor agonist. Muir, D.F., McCann, G.P., Swan, L., Clark, A.L., Hillis, W.S. Clin. Pharmacol. Ther. (1999) [Pubmed]
  16. Molecular cloning and pharmacological characterization of guinea pig 5-HT1B and 5-HT1D receptors. Zgombick, J.M., Bard, J.A., Kucharewicz, S.A., Urquhart, D.A., Weinshank, R.L., Branchek, T.A. Neuropharmacology (1997) [Pubmed]
  17. Agonistic properties of alniditan, sumatriptan and dihydroergotamine on human 5-HT1B and 5-HT1D receptors expressed in various mammalian cell lines. Lesage, A.S., Wouters, R., Van Gompel, P., Heylen, L., Vanhoenacker, P., Haegeman, G., Luyten, W.H., Leysen, J.E. Br. J. Pharmacol. (1998) [Pubmed]
  18. F 11356, a novel 5-hydroxytryptamine (5-HT) derivative with potent, selective, and unique high intrinsic activity at 5-HT1B/1D receptors in models relevant to migraine. John, G.W., Pauwels, P.J., Perez, M., Halazy, S., Le Grand, B., Verscheure, Y., Valentin, J.P., Palmier, C., Wurch, T., Chopin, P., Marien, M., Kleven, M.S., Koek, W., Assie, M.B., Carilla-Durand, E., Tarayre, J.P., Colpaert, F.C. J. Pharmacol. Exp. Ther. (1999) [Pubmed]
  19. Polymorphisms in the 5'-untranslated region of the human serotonin receptor 1B (HTR1B) gene affect gene expression. Duan, J., Sanders, A.R., Molen, J.E., Martinolich, L., Mowry, B.J., Levinson, D.F., Crowe, R.R., Silverman, J.M., Gejman, P.V. Mol. Psychiatry (2003) [Pubmed]
  20. Genetic diversity of the human serotonin receptor 1B (HTR1B) gene. Sanders, A.R., Cao, Q., Taylor, J., Levin, T.E., Badner, J.A., Cravchik, A., Comeron, J.M., Naruya, S., Del Rosario, A., Salvi, D.A., Walczyk, K.A., Mowry, B.J., Levinson, D.F., Crowe, R.R., Silverman, J.M., Gejman, P.V. Genomics (2001) [Pubmed]
  21. 5-HT1B receptor-mediated contractions in human temporal artery: evidence from selective antagonists and 5-HT receptor mRNA expression. Verheggen, R., Hundeshagen, A.G., Brown, A.M., Schindler, M., Kaumann, A.J. Br. J. Pharmacol. (1998) [Pubmed]
  22. Cloning and expression of the human 5-HT1B-type receptor gene. Mochizuki, D., Yuyama, Y., Tsujita, R., Komaki, H., Sagai, H. Biochem. Biophys. Res. Commun. (1992) [Pubmed]
  23. Magnitude of 5-HT1B and 5-HT1A receptor activation in guinea-pig and rat brain: evidence from sumatriptan dimer-mediated [35S]GTPgammaS binding responses. Dupuis, D.S., Perez, M., Halazy, S., Colpaert, F.C., Pauwels, P.J. Brain Res. Mol. Brain Res. (1999) [Pubmed]
  24. Could the 5-HT1B receptor inverse agonism affect learning consolidation? Meneses, A. Neuroscience and biobehavioral reviews. (2001) [Pubmed]
  25. Detection of a novel serotonin receptor subtype (5-HT1E) in human brain: interaction with a GTP-binding protein. Leonhardt, S., Herrick-Davis, K., Titeler, M. J. Neurochem. (1989) [Pubmed]
  26. Conversion of the human 5-HT1D beta serotonin receptor to the rat 5-HT1B ligand-binding phenotype by Thr355Asn site directed mutagenesis. Metcalf, M.A., McGuffin, R.W., Hamblin, M.W. Biochem. Pharmacol. (1992) [Pubmed]
  27. Site-directed mutagenesis of the 5-HT1B receptor increases the affinity of 5-HT for the agonist low-affinity conformation and reduces the intrinsic activity of 5-HT. Grånäs, C., Nordquist, J., Mohell, N., Larhammar, D. Eur. J. Pharmacol. (2001) [Pubmed]
  28. The First Luminal Domain of Vesicular Monoamine Transporters Mediates G-protein-dependent Regulation of Transmitter Uptake. Brunk, I., Blex, C., Rachakonda, S., H??ltje, M., Winter, S., Pahner, I., Walther, D.J., Ahnert-Hilger, G. J. Biol. Chem. (2006) [Pubmed]
  29. Association between the 5HT1B receptor gene (HTR1B) and the inattentive subtype of ADHD. Smoller, J.W., Biederman, J., Arbeitman, L., Doyle, A.E., Fagerness, J., Perlis, R.H., Sklar, P., Faraone, S.V. Biol. Psychiatry (2006) [Pubmed]
  30. Ergotamine and dihydroergotamine: history, pharmacology, and efficacy. Silberstein, S.D., McCrory, D.C. Headache. (2003) [Pubmed]
  31. Pharmacology of cloned human 5-HT1D receptor-mediated functional responses in stably transfected rat C6-glial cell lines: further evidence differentiating human 5-HT1D and 5-HT1B receptors. Pauwels, P.J., Palmier, C., Wurch, T., Colpaert, F.C. Naunyn Schmiedebergs Arch. Pharmacol. (1996) [Pubmed]
  32. Human 5-HT1B receptor stimulated inositol phospholipid hydrolysis in CHO cells: synergy with Gq-coupled receptors. Dickenson, J.M., Hill, S.J. Eur. J. Pharmacol. (1998) [Pubmed]
  33. Signal transduction differences between 5-hydroxytryptamine type 2A and type 2C receptor systems. Berg, K.A., Clarke, W.P., Sailstad, C., Saltzman, A., Maayani, S. Mol. Pharmacol. (1994) [Pubmed]
  34. Functional effects of the muscarinic receptor agonist, xanomeline, at 5-HT1 and 5-HT2 receptors. Watson, J., Brough, S., Coldwell, M.C., Gager, T., Ho, M., Hunter, A.J., Jerman, J., Middlemiss, D.N., Riley, G.J., Brown, A.M. Br. J. Pharmacol. (1998) [Pubmed]
  35. 5-HT 1B/D receptor antagonists. Pauwels, P.J. Gen. Pharmacol. (1997) [Pubmed]
  36. Molecular cloning of a human serotonin receptor (S12) with a pharmacological profile resembling that of the 5-HT1D subtype. Levy, F.O., Gudermann, T., Perez-Reyes, E., Birnbaumer, M., Kaumann, A.J., Birnbaumer, L. J. Biol. Chem. (1992) [Pubmed]
  37. Contractile 5-HT1B receptors in human cerebral arteries: pharmacological characterization and localization with immunocytochemistry. Nilsson, T., Longmore, J., Shaw, D., Olesen, I.J., Edvinsson, L. Br. J. Pharmacol. (1999) [Pubmed]
  38. 5-hydroxytryptamine receptors mediating contraction in human small muscular pulmonary arteries: importance of the 5-HT1B receptor. Morecroft, I., Heeley, R.P., Prentice, H.M., Kirk, A., MacLean, M.R. Br. J. Pharmacol. (1999) [Pubmed]
  39. Polymorphism of the serotonin 5-HT1B receptor gene (HTR1B) associated with minimum lifetime body mass index in women with bulimia nervosa. Levitan, R.D., Kaplan, A.S., Masellis, M., Basile, V.S., Walker, M.L., Lipson, N., Siegel, G.I., Woodside, D.B., Macciardi, F.M., Kennedy, S.H., Kennedy, J.L. Biol. Psychiatry (2001) [Pubmed]
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