5-HT4 receptor

5-HT4受容体、5-HT4レセプター、セロトニン4受容体、セロトニン4レセプター

関

5-HT4 serotonin receptor

WordNet

1. the 8th letter of the Roman alphabet (同)h
2. a cellular structure that is postulated to exist in order to mediate between a chemical agent that acts on nervous tissue and the physiological response

PrepTutorEJDIC

1. hydrogenの化学記号
2. 鉛筆の硬度 / 《俗》heroin
3. =sense organ / 受信装置

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/03/17 11:59:25」(JST)

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HTR4
Identifiers
Aliases	HTR4, 5-HT4, 5-HT4R, 5-HT4 receptor, 5-hydroxytryptamine receptor 4
External IDs	MGI: 109246 HomoloGene: 20243 GeneCards: HTR4
Targeted by Drug
vilazodone, pathogen, 5-methoxytryptamine, α-methyl-5-HT, mosapride, renzapride, zacopride, prucalopride, RS 67333, gr-113808, piboserod, SB 204070
Gene ontology Molecular function • G-protein coupled receptor activity • signal transducer activity • G-protein coupled serotonin receptor activity • trace-amine receptor activity Cellular component • cytoplasm • integral component of membrane • endosome • plasma membrane • integral component of plasma membrane • membrane Biological process • gamma-aminobutyric acid signaling pathway • G-protein coupled receptor signaling pathway • G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger • regulation of appetite • signal transduction • chemical synaptic transmission • G-protein coupled serotonin receptor signaling pathway Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3360	15562
Ensembl	ENSG00000164270	ENSMUSG00000026322
UniProt	Q13639	P97288
RefSeq (mRNA)	NM_000870 NM_001040169 NM_001040172 NM_001040173 NM_001040174 NM_001286410 NM_199453	NM_008313
RefSeq (protein)	NP_000861 NP_001035259 NP_001035262 NP_001035263 NP_001273339 NP_955525	NP_032339.2 NP_032339
Location (UCSC)	Chr 5: 148.45 – 148.68 Mb	Chr 18: 62.32 – 62.47 Mb
PubMed search
Wikidata
View/Edit Human		View/Edit Mouse

5-Hydroxytryptamine receptor 4 is a protein that in humans is encoded by the HTR4 gene.

Function

This gene is a member of the family of human serotonin receptors, which are G protein-coupled receptors that stimulate cAMP production in response to serotonin (5-hydroxytryptamine). The gene product is a glycosylated transmembrane protein that functions in both the peripheral and central nervous system to modulate the release of various neurotransmitters. Multiple transcript variants encoding proteins with distinct C-terminal sequences have been described, but the full-length nature of some transcript variants has not been determined.

Location

The receptor is located in the alimentary tract, urinary bladder, heart and adrenal gland as well as the central nervous system (CNS). In the CNS the receptor appears in the putamen, caudate nucleus, nucleus accumbens, globus pallidus, and substantia nigra, and to a lesser extent in the neocortex, raphe, pontine nuclei, and some areas of the thalamus. It has not been found in the cerebellum.

Isoforms

Internalization is isoform-specific.

Ligands

Several drugs that act as 5-HT₄ selective agonists have recently been introduced into use in both scientific research and clinical medicine. Some drugs that act as 5-HT₄ agonists are also active as 5-HT₃ antagonists, such as mosapride, metoclopramide, renzapride, and zacopride, and so these compounds cannot be considered highly selective. Research in this area is ongoing.

SB-207,145 radiolabeled with carbon-11 is used as a radioligand for 5-HT₄ in positron emission tomography pig and human studies.

Agonists

• BIMU-8
• Cisapride
• CJ-033,466 - partial agonist
• ML-10302
• Mosapride
• Prucalopride
• Renzapride
• RS-67506
• RS-67333 - partial agonist
• SL65.0155 - partial agonist
• Tegaserod
• Zacopride
• Metoclopramide
• Sulpiride

Antagonists

• Piboserod
• GR-113,808 (1-methyl-1H-indole-3-carboxylic acid, [1-[2-[(methylsulfonyl)amino]ethyl]-4-piperidinyl]methyl ester)
• GR-125,487
• RS-39604 (1-[4-Amino-5-chloro-2-(3,5-dimethoxyphenyl)methyloxy]-3-[1-[2-methylsulphonylamino]piperidin-4-yl]propan-1-one)
• SB-203,186
• SB-204,070
• ([Methoxy-¹¹C]1-butylpiperidin-4-yl)methyl 4-amino-3-methoxybenzoate
• Chamomile (ethanol extract)

See also

• 5-HT receptor
• 5-HT₁ receptor
• 5-HT₂ receptor
• 5-HT₃ receptor
• 5-HT₅ receptor
• 5-HT₆ receptor
• 5-HT₇ receptor

References

Further reading

• Licht CL, 2009, Changes in the 5-HT₄ receptor in animal models of depression and antidepressant treatment, PhD thesis, University of Copenhagen.
• Ullmer C, Schmuck K, Kalkman HO, Lübbert H (August 1995). "Expression of serotonin receptor mRNAs in blood vessels". FEBS Letters. 370 (3): 215–21. doi:10.1016/0014-5793(95)00828-W. PMID 7656980. 
• Blondel O, Vandecasteele G, Gastineau M, Leclerc S, Dahmoune Y, Langlois M, Fischmeister R (August 1997). "Molecular and functional characterization of a 5-HT4 receptor cloned from human atrium". FEBS Letters. 412 (3): 465–74. doi:10.1016/S0014-5793(97)00820-X. PMID 9276448. 
• Van den Wyngaert I, Gommeren W, Verhasselt P, Jurzak M, Leysen J, Luyten W, Bender E (November 1997). "Cloning and expression of a human serotonin 5-HT4 receptor cDNA". Journal of Neurochemistry. 69 (5): 1810–9. doi:10.1046/j.1471-4159.1997.69051810.x. PMID 9349523. 
• Claeysen S, Faye P, Sebben M, Lemaire S, Bockaert J, Dumuis A (October 1997). "Cloning and expression of human 5-HT4S receptors. Effect of receptor density on their coupling to adenylyl cyclase". NeuroReport. 8 (15): 3189–96. doi:10.1097/00001756-199710200-00002. PMID 9351641. 
• Blondel O, Gastineau M, Dahmoune Y, Langlois M, Fischmeister R (June 1998). "Cloning, expression, and pharmacology of four human 5-hydroxytryptamine 4 receptor isoforms produced by alternative splicing in the carboxyl terminus". Journal of Neurochemistry. 70 (6): 2252–61. doi:10.1046/j.1471-4159.1998.70062252.x. PMID 9603189. 
• Cichon S, Kesper K, Propping P, Nöthen MM (1998). "Assignment of the human serotonin 4 receptor gene (HTR4) to the long arm of chromosome 5 (5q31-q33)". Molecular Membrane Biology. 15 (2): 75–8. doi:10.3109/09687689809027521. PMID 9724925. 
• Claeysen S, Sebben M, Becamel C, Bockaert J, Dumuis A (May 1999). "Novel brain-specific 5-HT4 receptor splice variants show marked constitutive activity: role of the C-terminal intracellular domain". Molecular Pharmacology. 55 (5): 910–20. PMID 10220570. 
• Bender E, Pindon A, van Oers I, Zhang YB, Gommeren W, Verhasselt P, Jurzak M, Leysen J, Luyten W (February 2000). "Structure of the human serotonin 5-HT4 receptor gene and cloning of a novel 5-HT4 splice variant". Journal of Neurochemistry. 74 (2): 478–89. doi:10.1046/j.1471-4159.2000.740478.x. PMID 10646498. 
• Mialet J, Berque-Bestel I, Eftekhari P, Gastineau M, Giner M, Dahmoune Y, Donzeau-Gouge P, Hoebeke J, Langlois M, Sicsic S, Fischmeister R, Lezoualc'h F (February 2000). "Isolation of the serotoninergic 5-HT4(e) receptor from human heart and comparative analysis of its pharmacological profile in C6-glial and CHO cell lines". British Journal of Pharmacology. 129 (4): 771–81. doi:10.1038/sj.bjp.0703101. PMC 1571890. PMID 10683202. 
• Bach T, Syversveen T, Kvingedal AM, Krobert KA, Brattelid T, Kaumann AJ, Levy FO (February 2001). "5HT4(a) and 5-HT4(b) receptors have nearly identical pharmacology and are both expressed in human atrium and ventricle". Naunyn-Schmiedeberg's Archives of Pharmacology. 363 (2): 146–60. doi:10.1007/s002100000299. PMID 11218067. 
• Medhurst AD, Lezoualc'h F, Fischmeister R, Middlemiss DN, Sanger GJ (June 2001). "Quantitative mRNA analysis of five C-terminal splice variants of the human 5-HT4 receptor in the central nervous system by TaqMan real time RT-PCR". Brain Research. Molecular Brain Research. 90 (2): 125–34. doi:10.1016/S0169-328X(01)00095-X. PMID 11406291. 
• Hiroi T, Hayashi-Kobayashi N, Nagumo S, Ino M, Okawa Y, Aoba A, Matsui H (November 2001). "Identification and characterization of the human serotonin-4 receptor gene promoter". Biochemical and Biophysical Research Communications. 289 (2): 337–44. doi:10.1006/bbrc.2001.5979. PMID 11716477. 
• Vilaró MT, Doménech T, Palacios JM, Mengod G (January 2002). "Cloning and characterization of a novel human 5-HT4 receptor variant that lacks the alternatively spliced carboxy terminal exon. RT-PCR distribution in human brain and periphery of multiple 5-HT4 receptor variants". Neuropharmacology. 42 (1): 60–73. doi:10.1016/S0028-3908(01)00154-X. PMID 11750916. 
• López-Rodríguez ML, Murcia M, Benhamú B, Olivella M, Campillo M, Pardo L (November 2001). "Computational model of the complex between GR113808 and the 5-HT4 receptor guided by site-directed mutagenesis and the crystal structure of rhodopsin". Journal of Computer-Aided Molecular Design. 15 (11): 1025–33. doi:10.1023/A:1014895611874. PMID 11989623. 
• Ohtsuki T, Ishiguro H, Detera-Wadleigh SD, Toyota T, Shimizu H, Yamada K, Yoshitsugu K, Hattori E, Yoshikawa T, Arinami T (2003). "Association between serotonin 4 receptor gene polymorphisms and bipolar disorder in Japanese case-control samples and the NIMH Genetics Initiative Bipolar Pedigrees". Molecular Psychiatry. 7 (9): 954–61. doi:10.1038/sj.mp.4001133. PMID 12399948. 
• Norum JH, Hart K, Levy FO (January 2003). "Ras-dependent ERK activation by the human G(s)-coupled serotonin receptors 5-HT4(b) and 5-HT7(a)". The Journal of Biological Chemistry. 278 (5): 3098–104. doi:10.1074/jbc.M206237200. PMID 12446729. 
• Cartier D, Lihrmann I, Parmentier F, Bastard C, Bertherat J, Caron P, Kuhn JM, Lacroix A, Tabarin A, Young J, Vaudry H, Lefebvre H (January 2003). "Overexpression of serotonin4 receptors in cisapride-responsive adrenocorticotropin-independent bilateral macronodular adrenal hyperplasia causing Cushing's syndrome". The Journal of Clinical Endocrinology and Metabolism. 88 (1): 248–54. doi:10.1210/jc.2002-021107. PMID 12519861. 
• Manzke T, Guenther U, Ponimaskin EG, Haller M, Dutschmann M, Schwarzacher S, Richter DW (July 2003). "5-HT4(a) receptors avert opioid-induced breathing depression without loss of analgesia". Science. 301 (5630): 226–9. doi:10.1126/science.1084674. PMID 12855812. 

External links

• "5-HT₄". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. 
• Human HTR4 genome location and HTR4 gene details page in the UCSC Genome Browser.

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

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. セロトニンモジュレータ：薬理学、投与、および副作用 serotonin modulators pharmacology administration and side effects
• 2. 選択的セロトニン再取り込み阻害剤：薬理学、投与方法、および副作用 selective serotonin reuptake inhibitors pharmacology administration and side effects
• 3. 制吐剤の特性 characteristics of antiemetic drugs
• 4. セロトニン症候群 serotonin syndrome
• 5. 麻酔後ケア病棟における合併症発生の概要 overview of complications occurring in the post anesthesia care unit

English Journal

• Discovery of TD-8954, a clinical stage 5-HT4 receptor agonist with gastrointestinal prokinetic properties.

• McKinnell RM, Armstrong SR, Beattie DT, Fatheree PR, Long DD, Marquess DG, Shaw JP, Vickery RG.SourceTheravance, Inc., 901 Gateway Blvd, South San Francisco, CA 94080, United States. Electronic address: mmckinnell@theravance.com.
• Bioorganic & medicinal chemistry letters.Bioorg Med Chem Lett.2013 Jul 15;23(14):4210-5. doi: 10.1016/j.bmcl.2013.05.018. Epub 2013 May 16.
• The discovery of a series of 5-HT4 receptor agonists based on a novel 2-alkylbenzimidazole aromatic core is described. Optimization of the 2-substituent of the benzimidazole ring led to a series of agonists with subnanomolar binding affinity and moderate-to-high intrinsic activity relative to that o
• PMID 23756062

• Chronic 5-HT4 receptor activation decreases Aβ production and deposition in hAPP/PS1 mice.

• Tesseur I, Pimenova AA, Lo AC, Ciesielska M, Lichtenthaler SF, De Maeyer JH, Schuurkes JA, D'Hooge R, De Strooper B.SourceCenter for Human Genetics, Leuven Research Institute for Neuroscience and Disease (LIND), University of Leuven, Leuven, Belgium ina.tesseur@med.kuleuven.be
• Neurobiology of aging.Neurobiol Aging.2013 Jul;34(7):1779-89. doi: 10.1016/j.neurobiolaging.2013.01.020. Epub 2013 Mar 6.
• Lowering the production and accumulation of Aβ has been explored as treatment for Alzheimer's disease (AD), because Aβ is postulated to play an important role in the pathogenesis of AD. 5-HT4 receptors are an interesting drug target in this regard, as their activation might stimulate α-secretase
• PMID 23474291

• Ozone exposure alters serotonin and serotonin receptor expression in the developing lung.

• Murphy SR, Schelegle ES, Miller LA, Hyde DM, Van Winkle LS.Source* Center for Health and the Environment.
• Toxicological sciences : an official journal of the Society of Toxicology.Toxicol Sci.2013 Jul;134(1):168-79. doi: 10.1093/toxsci/kft090. Epub 2013 Apr 9.
• Ozone, a pervasive environmental pollutant, adversely affects functional lung growth in children. Animal studies demonstrate that altered lung development is associated with modified signaling within the airway epithelial mesenchymal trophic unit, including mediators that can change nerve growth. We
• PMID 23570994

Japanese Journal

• A protein tyrosine kinase receptor, c-RET signaling pathway contributes to the enteric neurogenesis induced by a 5-HT₄ receptor agonist at an anastomosis after transection of the gut in rodents

• Goto Kei,Kawahara Isao,Kuniyasu Hiroki [他]
• The journal of physiological sciences 65(4), 377-383, 2015-07
• NAID 40020509938

• 炎症性腸疾患モデル動物における温度感受性受容体TRPV1とセロトニンシグナリングの変化

• 松本 健次郎
• 薬学雑誌. 乙号 134(11), 1165-1170, 2014
• … Hypersensitivity of afferent fibers occurs during inflammation, and therefore to gain insight into the alteration of receptors and channels, we examined receptors such as 5-HT receptors and transient receptor potential vanilloid type 1 (TRPV1), which are expressed in primary afferent neurons. …
• NAID 130004712972

• 排便と健康

• 浦尾 正彦
• 順天堂醫事雑誌 60(1), 16-24, 2014
• 便秘とは，排便の頻度が週2回以下で，便が硬く，排便困難，残便感がある状態といわれている．実際には放置されていたり自己流の対処をされていることが多い．が，便秘患者では労働生産性が障害されたり，肛門疾患や結腸癌などの様々なリスクも増加することが知られており，しっかり取り組むべき疾患である．慢性便秘は，症候性，薬剤性，器質性，機能性便秘などに分類される．症候性便秘は神経疾患，内分泌疾患の症状の一部として …
• NAID 130004684311

Related Links

• 5-HT4 receptor - Wikipedia, the free encyclopedia

5-hydroxytryptamine receptor 4 is a protein that in humans is encoded by the HTR4 gene. This gene is a member of the family of serotonin receptors, which are G protein coupled receptors that stimulate cAMP production in response to ...

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英

5-HT4 receptor

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5-HT4レセプター、5-HT4セロトニンレセプター、セロトニン4レセプター、セロトニン4受容体

「5-HT4レセプター」

　　[★]

英

5-HT4 receptor

関

5-HT4受容体、セロトニン4レセプター、セロトニン4受容体

「セロトニン4受容体」

　　[★]

英

5-HT4 receptor

関

5-HT4受容体、5-HT4レセプター、セロトニン4レセプター

「セロトニン4レセプター」

　　[★]

英

5-HT4 receptor

関

5-HT4受容体、5-HT4レセプター、セロトニン4受容体

「HT」

　　[★]

• 高血圧症 高血圧 hypertension
• 心移植 heart transplantation

「H」

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• 食道裂孔
• ヒスチジン
• 水素