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HTR1D
Identifiers
Aliases	HTR1D, 5-HT1D, HT1DA, HTR1DA, HTRL, RDC4, 5-HT1D receptor, 5-hydroxytryptamine receptor 1D
External IDs	OMIM: 182133; MGI: 96276; HomoloGene: 20240; GeneCards: HTR1D; OMA:HTR1D - orthologs
Gene location (Human)
Chr.	Chromosome 1 (human)
End	23,217,502 bp
Gene location (Mouse)
Chr.	Chromosome 4 (mouse)
End	136,171,709 bp
RNA expression pattern
	Top expressed in
	testicle; ; nucleus accumbens; ; putamen; ; duodenum; ; caudate nucleus; ; gallbladder; ; gonad; ; ganglionic eminence; ; stromal cell of endometrium; ; prefrontal cortex;
	Top expressed in
	paraventricular nucleus of thalamus; ; lumbar spinal ganglion; ; lateral habenular nucleus; ; ventral nuclear group; ; lateral preoptic nucleus; ; multiform layer of neocortex; ; medial habenular nucleus; ; ventral nucleus of lateral geniculate body; ; embryo; ; nucleus of lateral olfactory tract;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	G protein-coupled receptor activity; signal transducer activity; G protein-coupled serotonin receptor activity; neurotransmitter receptor activity; serotonin binding;
Cellular component	integral component of membrane; plasma membrane; integral component of plasma membrane; membrane; dendrite;
Biological process	intestine smooth muscle contraction; regulation of locomotion; smooth muscle contraction; G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger; regulation of behavior; adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; response to toxic substance; vasoconstriction; signal transduction; chemical synaptic transmission; G protein-coupled serotonin receptor signaling pathway; G protein-coupled receptor signaling pathway;
	Sources:Amigo / QuickGO
Orthologs
	3352
	15552
	ENSG00000179546
	ENSMUSG00000070687
	P28221
	Q61224
	NM_000864
	NM_001285482; NM_001285483; NM_001285484; NM_008309
	NP_000855
	NP_001272411; NP_001272412; NP_001272413; NP_032335
	Wikidata
View/Edit Human	View/Edit Mouse

百度而在这一过程中，至亲所发挥的作用，是不可取代的。

5-hydroxytryptamine (serotonin) receptor 1D, also known as HTR1D, is a 5-HT receptor, but also denotes the human gene encoding it.^[5] 5-HT_1D acts on the central nervous system, and affects locomotion and anxiety. It also induces vasoconstriction in the brain.

Tissue distribution

5HT_1D receptors are found at low levels in the basal ganglia (globus pallidus, substantia nigra, caudate putamen), the hippocampus, and in the cortex.^[6]

Structure

5HT_1D 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 5HT_1D 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 5HT_1D receptor. The gene has been localized on chromosome 1, region 1p34.3-36.3 ^[10]^[11]

Ligands

Agonists

Molecular modelling has provided a picture of the agonistic binding site of 5HT_1D. The amino acid residues within the receptor binding site region have been identified. This is a valuable guide to design potential 5HT_1D receptor agonists. When sumatriptan binds there is major conformational change in both ligand and receptor in the binding pocket.^[12]

5-(Nonyloxy)tryptamine^[13]
Sumatriptan (vasoconstrictor in migraine)
Ergotamine (vasoconstrictor in migraine)
Zolmitriptan
5-Carboxamidotryptamine (5-CT)
5-(t-Butyl)-N-methyltryptamine^[14]
CP-135807
CP-286601
PNU-109291 ((S)-3,4-Dihydro-1-[2-[4-(4-methoxyphenyl)-1-piperazinyl]ethyl]-N-methyl-1H-2-benzopyran-6-carboxamide)
PNU-142633 ((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-694247 (2-[5-[3-(4-Methylsulfonylamino)benzyl-1,2,4-oxadiazol-5-yl]-1H-indol-3-yl]ethanamine)
L-760790
L-772405

Antagonists

Ziprasidone (atypical antipsychotic) [1]
Methiothepin (antipsychotic)
Yohimbine (aphrodisiac)
Metergoline
BRL-15572
Vortioxetine (antidepressant)
GR-127935 (mixed 5-HT_1B/1D antagonist)
LY-310762
LY-367642
LY-456219
LY-456220

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000179546 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000070687 – 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.
^ "Entrez Gene: HTR1D 5-hydroxytryptamine (serotonin) receptor 1D".
^ 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.
^ 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.
^ Goadsby PJ (1998). "Serotonin 5-HT_1B/1D Receptor Agonists in Migraine: Comparative Pharmacology and Its Therapeutic Implications". CNS Drugs. 10 (4): 271–286. doi:10.2165/00023210-199810040-00005.
^ 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.
^ 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.
^ 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.
^ Bremner DH, Ringan NS, Wishart G (1997). "Modeling of the agonist binding site of serotonin human 5-HT_1A, 5-HT_1Dα and 5-HT_1Dβ receptors". European Journal of Medicinal Chemistry. 32 (1): 59–69. doi:10.1016/S0223-5234(97)84362-0.
^ 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.
^ 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.

External links

"5-HT_1D". 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.

Hamblin MW, Metcalf MA, McGuffin RW, Karpells S (April 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): 752–759. doi:10.1016/0006-291X(92)90654-4. PMID 1315531.
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.
Hamblin MW, Metcalf MA (August 1991). "Primary structure and functional characterization of a human 5-HT1D-type serotonin receptor". Molecular Pharmacology. 40 (2): 143–148. PMID 1652050.
Libert F, Passage E, Parmentier M, Simons MJ, Vassart G, Mattei MG (September 1991). "Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor". Genomics. 11 (1): 225–227. doi:10.1016/0888-7543(91)90125-X. PMID 1662665.
Libert F, Parmentier M, Lefort A, Dinsart C, Van Sande J, Maenhaut C, et al. (May 1989). "Selective amplification and cloning of four new members of the G protein-coupled receptor family". Science. 244 (4904): 569–572. Bibcode:1989Sci...244..569L. doi:10.1126/science.2541503. PMID 2541503.
Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, et al. (July 1999). "Characterization of single-nucleotide polymorphisms in coding regions of human genes". Nature Genetics. 22 (3): 231–238. doi:10.1038/10290. PMID 10391209. S2CID 195213008.
Salim K, Fenton T, Bacha J, Urien-Rodriguez H, Bonnert T, Skynner HA, et al. (May 2002). "Oligomerization of G-protein-coupled receptors shown by selective co-immunoprecipitation" (PDF). The Journal of Biological Chemistry. 277 (18): 15482–15485. doi:10.1074/jbc.M201539200. PMID 11854302.
Bergen AW, van den Bree MB, Yeager M, Welch R, Ganjei JK, Haque K, et al. (April 2003). "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. doi:10.1038/sj.mp.4001318. PMID 12740597. S2CID 22413624.

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

This transmembrane receptor-related article is a stub. You can help Wikipedia by expanding it.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000179546 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000070687 – Ensembl, 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.

[entrez-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.

[Millan-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.

[Goadsby-8] Goadsby PJ (1998). "Serotonin 5-HT_1B/1D Receptor Agonists in Migraine: Comparative Pharmacology and Its Therapeutic Implications". CNS Drugs. 10 (4): 271–286. doi:10.2165/00023210-199810040-00005.

[Foyes-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.

[Bremner-12] Bremner DH, Ringan NS, Wishart G (1997). "Modeling of the agonist binding site of serotonin human 5-HT_1A, 5-HT_1Dα and 5-HT_1Dβ receptors". European Journal of Medicinal Chemistry. 32 (1): 59–69. doi:10.1016/S0223-5234(97)84362-0.

[Glennon_et_al_94-13] 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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