5-hydroxytryptamine (serotonin) receptor 1D, also known as HTR1D, is a 5-HT receptor, but also denotes the human gene encoding it.[5] 5-HT1D acts on the central nervous system, and affects locomotion and anxiety. It also induces vasoconstriction in the brain.

HTR1D
Identifiers
AliasesHTR1D, 5-HT1D, HT1DA, HTR1DA, HTRL, RDC4, 5-HT1D receptor, 5-hydroxytryptamine receptor 1D
External IDsOMIM: 182133; MGI: 96276; HomoloGene: 20240; GeneCards: HTR1D; OMA:HTR1D - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000864

NM_001285482
NM_001285483
NM_001285484
NM_008309

RefSeq (protein)

NP_000855

NP_001272411
NP_001272412
NP_001272413
NP_032335

Location (UCSC)Chr 1: 23.19 – 23.22 MbChr 4: 136.15 – 136.17 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Tissue distribution

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5HT1D receptors are found at low levels in the basal ganglia (globus pallidus, substantia nigra, caudate putamen), the hippocampus, and in the cortex.[6]

Structure

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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.[7][8] 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.[9] 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 [10][11]

Ligands

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Agonists

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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.[12]

Antagonists

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See also

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References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000179546Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000070687Ensembl, 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. ^ "Entrez Gene: HTR1D 5-hydroxytryptamine (serotonin) receptor 1D".
  6. ^ Hoyer D (2019). "Serotonin receptors nomenclature". In Tricklebank MD, Daly E (eds.). The Serotonin System: History, Neuropharmacology, and Pathology. Academic Press. pp. 63–93. doi:10.1016/B978-0-12-813323-1.00004-9. ISBN 978-0-12-813323-1.
  7. ^ Millan MJ, Marin P, Bockaert J, Mannoury la Cour C (September 2008). "Signaling at G-protein-coupled serotonin receptors: recent advances and future research directions". Trends in Pharmacological Sciences. 29 (9): 454–64. doi:10.1016/j.tips.2008.06.007. PMID 18676031.
  8. ^ Goadsby PJ (1998). "Serotonin 5-HT1B/1D Receptor Agonists in Migraine: Comparative Pharmacology and Its Therapeutic Implications". CNS Drugs. 10 (4): 271–286. doi:10.2165/00023210-199810040-00005.
  9. ^ Glennon RA, Dukat M (2013). "Serotonin Receptors and Drugs Affecting Serotonergic Neurotransmission" (PDF). In Lippincott WW, Lemke TL, Williams DA, Roche VF, Zito SW (eds.). Foye's Principles of Medicinal Chemistry (7th ed.). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. pp. 368–376. ISBN 978-1-60913-345-0.
  10. ^ Jin H, Oksenberg D, Ashkenazi A, Peroutka SJ, Duncan AM, Rozmahel R, et al. (March 1992). "Characterization of the human 5-hydroxytryptamine1B receptor". The Journal of Biological Chemistry. 267 (9): 5735–5738. doi:10.1016/S0021-9258(18)42612-9. PMID 1348246.
  11. ^ Weinshank RL, Zgombick JM, Macchi MJ, Branchek TA, Hartig PR (April 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): 3630–3634. Bibcode:1992PNAS...89.3630W. doi:10.1073/pnas.89.8.3630. PMC 48922. PMID 1565658.
  12. ^ Bremner DH, Ringan NS, 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.
  13. ^ Glennon RA, Hong SS, Dukat M, Teitler M, Davis K (September 1994). "5-(Nonyloxy)tryptamine: a novel high-affinity 5-HT1D beta serotonin receptor agonist". Journal of Medicinal Chemistry. 37 (18): 2828–2830. doi:10.1021/jm00044a001. PMID 8071931.
  14. ^ Xu YC, Schaus JM, Walker C, Krushinski J, Adham N, Zgombick JM, et al. (February 1999). "N-Methyl-5-tert-butyltryptamine: A novel, highly potent 5-HT1D receptor agonist". Journal of Medicinal Chemistry. 42 (3): 526–531. doi:10.1021/jm9805945. PMID 9986723.
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  • "5-HT1D". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
  • Human HTR1D genome location and HTR1D gene details page in the UCSC Genome Browser.

Further reading

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This article incorporates text from the United States National Library of Medicine, which is in the public domain.