Biology:5-HT1D receptor
 Generic protein structure example |
5-hydroxytryptamine (serotonin) receptor 1D, also known as HTR1D, is a 5-HT receptor, but also denotes the human gene encoding it.[1] 5-HT1D acts on the central nervous system, and affects locomotion and anxiety. It also induces vasoconstriction in the brain.
Tissue distribution and function
5HT1D receptors are found at low levels in the basal ganglia (globus pallidus, substantia nigra, caudate putamen), the hippocampus, and in the cortex.[2]
Structure
5HT1D receptor is a G protein linked receptor that activates an intracellular messenger cascade to produce an inhibitory response by decreasing cellular levels of cAMP.[3][4] The 5HT1D is a 7-TM receptor. A large intercellular loop between TM-5 and TM-6 is believed to be associated with coupling to a second messenger. Agonists might bind in a manner that utilizes an aspartate residue in TM-3 and residues in the TM-4, TM-5 and TM-6.[5] A human clone containing an intronless open reading frame was found to encode 377 amino acids of the 5HT1D receptor. The gene has been localized on chromosome 1, region 1p34.3-36.3 [6][7]
Ligands
Agonists
Molecular modelling has provided a picture of the agonistic binding site of 5HT1D. The amino acid residues within the receptor binding site region have been identified. This is a valuable guide to design potential 5HT1D receptor agonists. When sumatriptan binds there is major conformational change in both ligand and receptor in the binding pocket.[8]
- 5-(Nonyloxy)tryptamine[9]
- Sumatriptan (vasoconstrictor in migraine)
- Ergotamine (vasoconstrictor in migraine)
- 5-Carboxamidotryptamine (5-CT)
- 5-(t-Butyl)-N-methyltryptamine[10]
- CP-135,807
- CP-286,601
- PNU-109,291 ((S)-3,4-Dihydro-1-[2-[4-(4-methoxyphenyl)-1-piperazinyl]ethyl]-N-methyl-1H-2-benzopyran-6-carboxamide)
- PNU-142,633 ((1S)-1-[2-[4-[4-(Aminocarbonyl)phenyl]-1-piperazinyl]ethyl]-3,4-dihydro-N-methyl-1H-2-benzopyran-6-carboxamide)
- GR-46611 (3-[3-(2-Dimethylaminoethyl)-1H-indol-5-yl]-N-(4-methoxybenzyl)acrylamide)
- L-694,247 (2-[5-[3-(4-Methylsulfonylamino)benzyl-1,2,4-oxadiazol-5-yl]-1H-indol-3-yl]ethanamine)
- L-772,405
Antagonists
- Ziprasidone (atypical antipsychotic) [1]
- Methiothepin (antipsychotic)
- Yohimbine (aphrodisiac)
- Metergoline
- BRL-15572
- Vortioxetine (antidepressant)
- GR-127,935 (mixed 5-HT1B/1D antagonist)
- LY-310,762
- LY-367,642
- LY-456,219
- LY-456,220
See also
References
- ↑ "Entrez Gene: HTR1D 5-hydroxytryptamine (serotonin) receptor 1D". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3352.
- ↑ Hoyer, D., 2019. Serotonin receptors nomenclature. The Serotonin System, pp. 63–93.
- ↑ Millan, M.J., et al., Signaling at G-protein-coupled serotonin receptors: recent advances and future research directions. Trends in Pharmacological Sciences, 2008. 29(9): pp. 454–464.
- ↑ Goadsby, P.J., Serotonin 5-HT1B/1D receptor agonists in migraine - Comparative pharmacology and its therapeutic implications. Cns Drugs, 1998. 10(4): p. 271-286.
- ↑ Lippincott, W. W., Lemke, T. L., Williams, D. A., Roche, V. F., & Zito, S. W. (2013). Foye's Principles of Medicinal Chemistry: Lippincott Williams & Wilkins: 368-376.
- ↑ Jin, H.; Oksenberg, D.; Ashkenazi, A.; Peroutka, S. J.; Duncan, A. M.; Rozmahel, R.; O'Dowd, B. F. (1992). "Characterization of the human 5-hydroxytryptamine1B receptor". J Biol Chem 267 (9): 5735–5738. doi:10.1016/S0021-9258(18)42612-9. PMID 1348246.
- ↑ Weinshank, R. L.; Zgombick, J. M.; Macchi, M. J.; Branchek, T. A.; Hartig, P. R. (1992). "Human Serotonin-1d Receptor Is Encoded by a Subfamily of 2 Distinct Genes – 5-Ht(1d-Alpha) and 5-Ht(1d-Beta)". Proceedings of the National Academy of Sciences of the United States of America 89 (8): 3630–3634. doi:10.1073/pnas.89.8.3630. PMID 1565658. Bibcode: 1992PNAS...89.3630W.
- ↑ Bremner, D. H.; Ringan, N. S.; Wishart, G. (1997). "Modeling of the agonist binding site of serotonin human 5-HT1A, 5-HT1Dα and 5-HT1Dβ receptors". European Journal of Medicinal Chemistry 32 (1): 59–69. doi:10.1016/S0223-5234(97)84362-0.
- ↑ "5-(Nonyloxy)tryptamine: a novel high-affinity 5-HT1D beta serotonin receptor agonist". Journal of Medicinal Chemistry 37 (18): 2828–30. Sep 1994. doi:10.1021/jm00044a001. PMID 8071931.
- ↑ "N-Methyl-5-tert-butyltryptamine: A novel, highly potent 5-HT1D receptor agonist". Journal of Medicinal Chemistry 42 (3): 526–31. Feb 1999. doi:10.1021/jm9805945. PMID 9986723.
External links
- "5-HT1D". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2314.
- Human HTR1D genome location and HTR1D gene details page in the UCSC Genome Browser.
Further reading
- "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. Apr 1992. doi:10.1016/0006-291X(92)90654-4. PMID 1315531.
- "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. Apr 1992. doi:10.1073/pnas.89.8.3630. PMID 1565658. Bibcode: 1992PNAS...89.3630W.
- "Primary structure and functional characterization of a human 5-HT1D-type serotonin receptor". Molecular Pharmacology 40 (2): 143–8. Aug 1991. PMID 1652050.
- "Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor". Genomics 11 (1): 225–7. Sep 1991. doi:10.1016/0888-7543(91)90125-X. PMID 1662665.
- "Selective amplification and cloning of four new members of the G protein-coupled receptor family". Science 244 (4904): 569–72. May 1989. doi:10.1126/science.2541503. PMID 2541503. Bibcode: 1989Sci...244..569L.
- "Characterization of single-nucleotide polymorphisms in coding regions of human genes". Nature Genetics 22 (3): 231–8. Jul 1999. doi:10.1038/10290. PMID 10391209.
- "Oligomerization of G-protein-coupled receptors shown by selective co-immunoprecipitation". The Journal of Biological Chemistry 277 (18): 15482–5. May 2002. doi:10.1074/jbc.M201539200. PMID 11854302.
- "Candidate genes for anorexia nervosa in the 1p33-36 linkage region: serotonin 1D and delta opioid receptor loci exhibit significant association to anorexia nervosa". Molecular Psychiatry 8 (4): 397–406. 2003. doi:10.1038/sj.mp.4001318. PMID 12740597.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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