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HTR1F  -  5-hydroxytryptamine (serotonin) receptor...

Homo sapiens

Synonyms: 5-HT-1F, 5-HT1F, 5-hydroxytryptamine receptor 1F, 5HT6, HTR1EL, ...
 
 
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Disease relevance of HTR1F

 

Psychiatry related information on HTR1F

  • The lack of significant mutations in patients suffering from schizophrenia and bipolar affective disorder indicates that the 5-HT1F receptor is not commonly involved in the etiology of these diseases [3].
  • Sequencing of two positional candidate genes, 5HT1F and DRD3, did not support their role in dyslexia [4].
 

High impact information on HTR1F

  • HeLa cells transfected with the MR77 gene exhibited inhibition of adenylate cyclase in response to serotonin [5].
  • These properties distinguish this receptor from any previously characterized and establish a fifth 5-HT1-like receptor subtype (5-HT1F) coupled to the inhibition of adenylate cyclase [6].
  • Cloning of another human serotonin receptor (5-HT1F): a fifth 5-HT1 receptor subtype coupled to the inhibition of adenylate cyclase [6].
  • MR77 thus represents a 5-HT receptor of the 5-HT1 class, and we propose that, based on the pharmacological characterization, MR77 represents an additional 5-HT1E-like receptor [5].
  • MR77 is expressed at low levels throughout the brain, with the greatest expression in the cortex, hippocampus, and striatum [5].
 

Chemical compound and disease context of HTR1F

 

Biological context of HTR1F

 

Anatomical context of HTR1F

 

Associations of HTR1F with chemical compounds

  • The 5-HT1F receptor, which is present in both human vascular and neuronal tissue, may mediate the therapeutic effect and/or side-effects of sumatriptan [1].
  • Neural 5-HT1D and/or 5-HT1F receptors localized pre-junctionally on trigeminovascular afferents appear to mediate the triptan-induced inhibition of the neurogenic inflammatory response, with possible additional sites of action for brain penetrant 5-HT1 receptor agonists in inhibiting the transmission of pain centrally [13].
  • Alniditan showed moderate-to-low or no affinity for other investigated receptors; sumatriptan showed additional binding to 5-HT1F receptors [14].
  • Possible antimigraine mechanisms of action of the 5HT1F receptor agonist LY334370 [15].
  • These results suggest that selective 5-HT1D and 5-HT1F receptor agonists might represent new antimigraine drugs devoid of cerebro- and cardiovascular effects [16].
 

Other interactions of HTR1F

  • However, neither 5-HT1F mRNA nor 5-HT2C mRNA was detected in any patient [17].
  • Expression of 5-HT1F and 5-HT2A receptor mRNAs was never detected in any of the microvascular cell cultures [10].
  • The recent availability of subtype selective 5-HT1D and 5-HT1F receptor agonists should allow a further test of the neural/vascular hypothesis and could possibly lead to antimigraine drugs with a safer cardiovascular profile [13].
  • 6. 4. RT-PCR studies in human coronary arteries showed a strong signal for the 5-HT1B receptor while message for the 5-HT1F receptor was weak and less frequently detected [16].
  • Indoline and 1,2-benzisoxazole systems also provided potent 5-HT1F receptor agonists, and the 5-HT1A receptor selectivity of the indoline- and 1,2-benzisoxazole-based 5-HT1F receptor agonists could be improved with modification of the benzoyl moiety of the benzamides [18].
 

Analytical, diagnostic and therapeutic context of HTR1F

  • The 5-HT1F receptor gene was localized using a monochromosomal mapping panel, followed by a radiation-reduced hybrid mapping and fluorescent in situ hybridization [1].
  • PCR products indicative of the 5-HT1F receptor message were detected by gel electrophoresis in three brain vessel preparations and confirmed in the other four by Southern blot hybridization [11].
  • The labelling conditions to visualize 5-HT1F receptors in guinea pig brain, namely 3H-sumatriptan in the presence of 10(-8) M 5-CT to block 5-HT1D receptors, are suitable for visualizing this receptor, since the results agreed with those observed by in situ hybridization [19].

References

  1. Chromosomal localization of the 5-HT1F receptor gene: no evidence for involvement in response to sumatriptan in migraine patients. Maassen VanDenBrink, A., Vergouwe, M.N., Ophoff, R.A., Naylor, S.L., Dauwerse, H.G., Saxena, P.R., Ferrari, M.D., Frants, R.R. Am. J. Med. Genet. (1998) [Pubmed]
  2. Cloning and characterization of the guinea pig 5-HT1F receptor subtype: a comparison of the pharmacological profile to the human species homolog. Adham, N., Bard, J.A., Zgombick, J.M., Durkin, M.M., Kucharewicz, S., Weinshank, R.L., Branchek, T.A. Neuropharmacology (1997) [Pubmed]
  3. Systematic screening for mutations in the human serotonin 1F receptor gene in patients with bipolar affective disorder and schizophrenia. Shimron-Abarbanell, D., Harms, H., Erdmann, J., Albus, M., Maier, W., Rietschel, M., Körner, J., Weigelt, B., Franzek, E., Sander, T., Knapp, M., Propping, P., Nöthen, M.M. Am. J. Med. Genet. (1996) [Pubmed]
  4. A dominant gene for developmental dyslexia on chromosome 3. Nopola-Hemmi, J., Myllyluoma, B., Haltia, T., Taipale, M., Ollikainen, V., Ahonen, T., Voutilainen, A., Kere, J., Widén, E. J. Med. Genet. (2001) [Pubmed]
  5. Molecular cloning and functional expression of 5-HT1E-like rat and human 5-hydroxytryptamine receptor genes. Lovenberg, T.W., Erlander, M.G., Baron, B.M., Racke, M., Slone, A.L., Siegel, B.W., Craft, C.M., Burns, J.E., Danielson, P.E., Sutcliffe, J.G. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  6. Cloning of another human serotonin receptor (5-HT1F): a fifth 5-HT1 receptor subtype coupled to the inhibition of adenylate cyclase. Adham, N., Kao, H.T., Schecter, L.E., Bard, J., Olsen, M., Urquhart, D., Durkin, M., Hartig, P.R., Weinshank, R.L., Branchek, T.A. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  7. 5-HT1F receptor agonists in acute migraine treatment: a hypothesis. Ramadan, N.M., Skljarevski, V., Phebus, L.A., Johnson, K.W. Cephalalgia : an international journal of headache. (2003) [Pubmed]
  8. 5-HT1F receptor agonists inhibit neurogenic dural inflammation in guinea pigs. Johnson, K.W., Schaus, J.M., Durkin, M.M., Audia, J.E., Kaldor, S.W., Flaugh, M.E., Adham, N., Zgombick, J.M., Cohen, M.L., Branchek, T.A., Phebus, L.A. Neuroreport (1997) [Pubmed]
  9. Assignment of the human serotonin 1F receptor gene (HTR1F) to the short arm of chromosome 3 (3p13-p14.1). Erdmann, J., Shimron-Abarbanell, D., Shridhar, V., Smith, D.I., Propping, P., Nöthen, M.M. Mol. Membr. Biol. (1997) [Pubmed]
  10. Multiple microvascular and astroglial 5-hydroxytryptamine receptor subtypes in human brain: molecular and pharmacologic characterization. Cohen, Z., Bouchelet, I., Olivier, A., Villemure, J.G., Ball, R., Stanimirovic, D.B., Hamel, E. J. Cereb. Blood Flow Metab. (1999) [Pubmed]
  11. Differential expression of sumatriptan-sensitive 5-hydroxytryptamine receptors in human trigeminal ganglia and cerebral blood vessels. Bouchelet, I., Cohen, Z., Case, B., Séguéla, P., Hamel, E. Mol. Pharmacol. (1996) [Pubmed]
  12. Differential distribution of [3H]sumatriptan binding sites (5-HT1B, 5-HT1D and 5-HT1F receptors) in human brain: focus on brainstem and spinal cord. Castro, M.E., Pascual, J., Romón, T., del Arco, C., del Olmo, E., Pazos, A. Neuropharmacology (1997) [Pubmed]
  13. The biology of serotonin receptors: focus on migraine pathophysiology and treatment. Hamel, E. The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques. (1999) [Pubmed]
  14. Alniditan, a new 5-hydroxytryptamine1D agonist and migraine-abortive agent: ligand-binding properties of human 5-hydroxytryptamine1D alpha, human 5-hydroxytryptamine1D beta, and calf 5-hydroxytryptamine1D receptors investigated with [3H]5-hydroxytryptamine and [3H]alniditan. Leysen, J.E., Gommeren, W., Heylen, L., Luyten, W.H., Van de Weyer, I., Vanhoenacker, P., Haegeman, G., Schotte, A., Van Gompel, P., Wouters, R., Lesage, A.S. Mol. Pharmacol. (1996) [Pubmed]
  15. Possible antimigraine mechanisms of action of the 5HT1F receptor agonist LY334370. Shepheard, S., Edvinsson, L., Cumberbatch, M., Williamson, D., Mason, G., Webb, J., Boyce, S., Hill, R., Hargreaves, R. Cephalalgia : an international journal of headache. (1999) [Pubmed]
  16. No contractile effect for 5-HT1D and 5-HT1F receptor agonists in human and bovine cerebral arteries: similarity with human coronary artery. Bouchelet, I., Case, B., Olivier, A., Hamel, E. Br. J. Pharmacol. (2000) [Pubmed]
  17. Identification of mRNA for 5-HT1 and 5-HT2 receptor subtypes in human coronary arteries. Ishida, T., Hirata, K., Sakoda, T., Kawashima, S., Akita, H., Yokoyama, M. Cardiovasc. Res. (1999) [Pubmed]
  18. Design, synthesis and evaluation of bicyclic benzamides as novel 5-HT1F receptor agonists. Zhang, D., Kohlman, D., Krushinski, J., Liang, S., Ying, B.P., Reilly, J.E., Dinn, S.R., Wainscott, D.B., Nutter, S., Gough, W., Nelson, D.L., Schaus, J.M., Xu, Y.C. Bioorg. Med. Chem. Lett. (2004) [Pubmed]
  19. 5-HT receptors in mammalian brain: receptor autoradiography and in situ hybridization studies of new ligands and newly identified receptors. Mengod, G., Vilaró, M.T., Raurich, A., López-Giménez, J.F., Cortés, R., Palacios, J.M. Histochem. J. (1996) [Pubmed]
 
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