5-HT4 receptor

5-HT4 receptor (5-hidroksitriptaminski receptor 4) je protein koji je kod ljudi kodiran HTR4 genom.^[1][2]

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5-hidroksitriptaminski (serotoninski) receptor 4
Identifikatori
Simboli	HTR4; 5-HT4; 5-HT4R
Vanjski ID	OMIM: 602164 MGI: 109246 HomoloGene: 20243 IUPHAR: 5-HT4 GeneCards: HTR4 Gene
Ontologija gena Molekularna funkcija • aktivnost rodopsinu-sličnog receptora • receptorska aktivnost • adrenoceptorska aktivnost • serotoninska receptorska aktivnost Celularna komponenta • membranska frakcija • integralno sa ćelijskom membranom • membrana • integralno sa membranom Biološki proces • prenos signala • signalni put G-protein spregnutog receptora • G-proteinska signalizacija, spregnuta sa cikličnim nukleotidnim sekundarnim glasnikom
Pregled RNK izražavanja
podaci
Ortolozi
Vrsta	Čovek	Miš
Entrez	3360	15562
Ensembl	ENSG00000164270	ENSMUSG00000026322
UniProt	Q13639	Q3URB5
RefSeq (mRNA)	NM_000870	NM_008313
RefSeq (protein)	NP_000861	NP_032339
Lokacija (UCSC)	Chr 5: 147.81 - 148.01 Mb	Chr 18: 62.45 - 62.59 Mb
PubMed pretraga

Ovaj gen je član familije serotoninskih receptora, koji su G protein spregnuti receptori koji stimulišu cAMP produkciju u responsu na vezivanje serotonina (5-hidroksitriptamina). To je glikolizirani transmembranski protein koji funkcioniše u perifernom i centralnom nervnom sistemu gde modulara otpuštanje raznih neurotransmitera. Postoji više transkriptnih varijanti koje kodiraju proteine sa distinktnim C-terminalnim sekvencama.^[3]

Lokacija

Receptor je lociran u alimentarnom traktu, mokraćnoj bešiki, srcu i nadbubrežnoj žlezdi, kao i u centralnom nervnom sistemu (CNS).^[4] On nije nađen u cerebelumu.^[5]

Izoforme

Internalizacija je specifična za pojedine izoforme.^[6]

Ligandi

Postoji nekoliko lekova kaji deluju na 5-HT₄ kao selektivni agonisti. Oni se koriste u naučnim istraživanjima i kliničkoj medicini. Neki od lekova koji deluju kao 5-HT₄ agonisti su isto tako aktivni kao 5-HT₃ antagonisti, npr, mosaprid, metoclopramid, renzaprid i zacoprid.^[7] SB-207,145 radio obeležen sa ugljenikom-11 se koristi kao radioligand za 5-HT₄ ispitivanja pozitronskom emisionom tomografijom na životinjama^[8] i u humanim ispitivanjima.^[9].

Agonisti

• BIMU-8
• Cisaprid
• CJ-033,466
• Mosaprid
• Prukaloprid
• Renzaprid
• RS-67506
• RS-67333 - parcijalni agonist
• SL65.0155 - parcijalni agonist
• Tegaserod
• Zakoprid

Antagonisti

• Piboserod
• GR-113,808 (1-metil-1H-indol-3-karboksilna kiselina, [1-[2-[(metilsulfonil)amino]etil]-4-piperidinil]metil ester)^[10]
• GR-125,487
• RS-39604 (1-[4-Amino-5-hloro-2-(3,5-dimetoksifenil)metiloksi]-3-[1-[2-metilsulfonilamino]piperidin-4-il]propan-1-on)
• SB-203,186
• ([Metoksi-¹¹C]1-butilpiperidin-4-jil)metil 4-amino-3-metoksibenzoat^[11]

Povezano

• 5-HT receptor

Reference

1. Claeysen S, Faye P, Sebben M, Lemaire S, Bockaert J, Dumuis A, Taviaux S (December 1997). „Assignment of 5-hydroxytryptamine receptor (HTR4) to human chromosome 5 bands q31→q33 by in situ hybridization.”. Cytogenet Cell Genet 78 (2): 133–4. DOI:10.1159/000134646. PMID 9371406.
2. , Blondel O, Vandecasteele G, Gastineau M, Leclerc S, Dahmoune Y, Langlois M, Fischmeister R (September 1997). „Molecular and functional characterization of a 5-HT4 receptor cloned from human atrium.”. FEBS Lett 412 (3): 465–74. DOI:10.1016/S0014-5793(97)00820-X. PMID 9276448.
3. „Entrez Gene: HTR4 5-hydroxytryptamine (serotonin) receptor 4”.
4. S. S. Hegde, R. M. Eglen (1996-01-10). „Peripheral 5-HT4 receptors”. The FASEB journal 10 (12): 1398–1407. PMID 8903510.
5. Katarina Varnäs, Christer Halldin, Victor W. Pike, Håkan Hall (2003). „Distribution of 5-HT₄ receptors in the postmortem human brain–an autoradiographic study using [¹²⁵]SB 207710”. European Neuropsychopharmacology 13: 228–234. DOI:10.1016/S0924-977X(03)00009-9.
6. PMID 19922792
7. Pellissier LP, Sallander J, Campillo M, Gaven F, Queffeulou E, Pillot M, Dumuis A, Claeysen S, Bockaert J, Pardo L (April 2009). „Conformational toggle switches implicated in basal constitutive and agonist-induced activated states of 5-hydroxytryptamine-4 receptors”. Molecular Pharmacology 75 (4): 982–90. DOI:10.1124/mol.108.053686. PMID 19168624.
8. B. R. Kornum, N. M. Lind, N. Gillings, Lisbeth Marner, F. Andersen, Gitte Moos Knudsen (September 2008). „Evaluation of the novel 5-HT(4) receptor PET ligand [(11)C]SB207145 in the Gottingen minipig”. Journal of Cerebral Blood Flow and Metabolism 29 (1): 186. DOI:10.1038/jcbfm.2008.110. PMID 18797470.
9. Lisbeth Marner, Nic Gillings, Roger Gunn, Robert Comley, William Baaré, Steen Hasselbalch and Gitte Knudsen (2008-01-05). „Quantification of 11C-SB207145-PET for 5-HT4 receptors in the human brain: Preliminary results”. Journal of Nuclear Medicine 48 (Supplement 2) (Supplement 2): 159P. Arhivirano iz originala na datum 2016-03-03. Pristupljeno 2014-05-02.
10. Gale JD, Grossman CJ, Whitehead, JW Oxford AW, Bunce KT, Humphrey PP (1994). „GR113808: a novel, selective antagonist with high affinity at the 5-HT4 receptor.”. British journal of pharmacology 111 (1): 332–8. PMC 1910004. PMID 8012715.
11. Xu R, Hong J, Morse CL, Pike VW (2010-10-14). „Synthesis, structure-affinity relationships, and radiolabeling of selective high-affinity 5-HT4 receptor ligands as prospective imaging probes for positron emission tomography”. J Med Chem 53 (19): 7035-47. PMID 20812727.

Literatura

• Cecilie Löe Licht, Changes in the 5-HT₄ receptor in animal models of depression and antidepressant treatment, PhD thesis, Faculty of Health Sciences, University of Copenhagen. Submitted 2008 October.
• Ullmer C, Schmuck K, Kalkman HO, Lübbert H (1995). „Expression of serotonin receptor mRNAs in blood vessels.”. FEBS Lett. 370 (3): 215–21. DOI:10.1016/0014-5793(95)00828-W. PMID 7656980.
• Blondel O, Vandecasteele G, Gastineau M, et al. (1997). „Molecular and functional characterization of a 5-HT4 receptor cloned from human atrium.”. FEBS Lett. 412 (3): 465–74. DOI:10.1016/S0014-5793(97)00820-X. PMID 9276448.
• Van den Wyngaert I, Gommeren W, Verhasselt P, et al. (1997). „Cloning and expression of a human serotonin 5-HT4 receptor cDNA.”. J. Neurochem. 69 (5): 1810–9. DOI:10.1046/j.1471-4159.1997.69051810.x. PMID 9349523.
• Claeysen S, Faye P, Sebben M, et al. (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, et al. (1998). „Cloning, expression, and pharmacology of four human 5-hydroxytryptamine 4 receptor isoforms produced by alternative splicing in the carboxyl terminus.”. J. Neurochem. 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).”. Mol. Membr. Biol. 15 (2): 75–8. DOI:10.3109/09687689809027521. PMID 9724925.
• Claeysen S, Sebben M, Becamel C, et al. (1999). „Novel brain-specific 5-HT4 receptor splice variants show marked constitutive activity: role of the C-terminal intracellular domain.”. Mol. Pharmacol. 55 (5): 910–20. PMID 10220570.
• Bender E, Pindon A, van Oers I, et al. (2000). „Structure of the human serotonin 5-HT4 receptor gene and cloning of a novel 5-HT4 splice variant.”. J. Neurochem. 74 (2): 478–89. DOI:10.1046/j.1471-4159.2000.740478.x. PMID 10646498.
• Mialet J, Berque-Bestel I, Eftekhari P, et al. (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.”. Br. J. Pharmacol. 129 (4): 771–81. DOI:10.1038/sj.bjp.0703101. PMC 1571890. PMID 10683202.
• Bach T, Syversveen T, Kvingedal AM, et al. (2001). „5HT4(a) and 5-HT4(b) receptors have nearly identical pharmacology and are both expressed in human atrium and ventricle.”. Naunyn Schmiedebergs Arch. Pharmacol. 363 (2): 146–60. DOI:10.1007/s002100000299. PMID 11218067.
• Medhurst AD, Lezoualc'h F, Fischmeister R, et al. (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 Res. Mol. Brain Res. 90 (2): 125–34. DOI:10.1016/S0169-328X(01)00095-X. PMID 11406291.
• Hiroi T, Hayashi-Kobayashi N, Nagumo S, et al. (2002). „Identification and characterization of the human serotonin-4 receptor gene promoter.”. Biochem. Biophys. Res. Commun. 289 (2): 337–44. DOI:10.1006/bbrc.2001.5979. PMID 11716477.
• Vilaró MT, Doménech T, Palacios JM, Mengod G (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, et al. (2002). „Computational model of the complex between GR113808 and the 5-HT4 receptor guided by site-directed mutagenesis and the crystal structure of rhodopsin.”. J. Comput. Aided Mol. Des. 15 (11): 1025–33. DOI:10.1023/A:1014895611874. PMID 11989623.
• Ohtsuki T, Ishiguro H, Detera-Wadleigh SD, et al. (2003). „Association between serotonin 4 receptor gene polymorphisms and bipolar disorder in Japanese case-control samples and the NIMH Genetics Initiative Bipolar Pedigrees.”. Mol. Psychiatry 7 (9): 954–61. DOI:10.1038/sj.mp.4001133. PMID 12399948.
• Norum JH, Hart K, Levy FO (2003). „Ras-dependent ERK activation by the human G(s)-coupled serotonin receptors 5-HT4(b) and 5-HT7(a).”. J. Biol. Chem. 278 (5): 3098–104. DOI:10.1074/jbc.M206237200. PMID 12446729.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). „Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.”. Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. DOI:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Cartier D, Lihrmann I, Parmentier F, et al. (2003). „Overexpression of serotonin4 receptors in cisapride-responsive adrenocorticotropin-independent bilateral macronodular adrenal hyperplasia causing Cushing's syndrome.”. J. Clin. Endocrinol. Metab. 88 (1): 248–54. DOI:10.1210/jc.2002-021107. PMID 12519861.
• Manzke T, Guenther U, Ponimaskin EG, et al. (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.

Spoljašnje veze

• „5-HT₄”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Arhivirano iz originala na datum 2016-06-05.