5-HT₄ receptor

5-hidroksitriptaminski (serotoninski) receptor 4
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
Entrez	3360
Ensembl	ENSG00000164270
UniProt	Q13639
RefSeq (mRNA)	NM_000870
RefSeq (protein)	NP_000861
Lokacija (UCSC)	Chr 5:; 147.81 - 148.01 Mb
PubMed pretraga	[1]

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

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]

Vidi još

5-HT receptor

Reference

^ Claeysen S, Faye P, Sebben M, Lemaire S, Bockaert J, Dumuis A, Taviaux S (1997). „Assignment of 5-hydroxytryptamine receptor (HTR4) to human chromosome 5 bands q31→q33 by in situ hybridization.” (PDF). Cytogenet Cell Genet. 78 (2): 133—4. PMID 9371406. doi:10.1159/000134646.
^ Blondel O, Vandecasteele G, Gastineau M, Leclerc S, Dahmoune Y, Langlois M, Fischmeister R (1997). „Molecular and functional characterization of a 5-HT4 receptor cloned from human atrium.” (PDF). FEBS Lett. 412 (3): 465—74. PMID 9276448. S2CID 23714426. doi:10.1016/S0014-5793(97)00820-X. ^{[мртва веза]}
^ „Entrez Gene: HTR4 5-hydroxytryptamine (serotonin) receptor 4”. Приступљено 1. 7. 2018.
^ Hegde, SS; Eglen, RM (1. 10. 1996). „Peripheral 5-HT4 receptors”. The FASEB Journal. 10 (12): 1398—1407. PMID 8903510. S2CID 21596751. doi:10.1096/fasebj.10.12.8903510. Пронађени су сувишни параметри: |author= и |last1= (помоћ); Пронађени су сувишни параметри: |author2= и |last2= (помоћ)
^ 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 (4): 228—234. PMID 12888181. S2CID 27945284. doi:10.1016/S0924-977X(03)00009-9.
^ Mnie-Filali, O.; Amraei, M. G.; Benmbarek, S.; Archer-Lahlou, E.; Peñas-Cazorla, R.; Vilaró, M. T.; Boye, S. M.; Piñeyro, G. (2010). „Serotonin 4 receptor (5-HT4R) internalization is isoform-specific: Effects of 5-HT and RS67333 on isoforms a and B”. Cellular Signalling. 22 (3): 501—509. PMID 19922792. doi:10.1016/j.cellsig.2009.11.004.
^ Pellissier LP, Sallander J, Campillo M, Gaven F, Queffeulou E, Pillot M, Dumuis A, Claeysen S, Bockaert J, Pardo L (2009). „Conformational toggle switches implicated in basal constitutive and agonist-induced activated states of 5-hydroxytryptamine-4 receptors” (PDF). Molecular Pharmacology. 75 (4): 982—90. PMID 19168624. S2CID 17957338. doi:10.1124/mol.108.053686.
^ Kornum, B. R.; N. M. Lind; N. Gillings; Marner, Lisbeth; F. Andersen; Gitte Moos Knudsen (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—196. PMID 18797470. S2CID 16196384. doi:10.1038/jcbfm.2008.110.
^ Lisbeth Marner, Nic Gillings, Roger Gunn, Robert Comley, William Baaré, Steen Hasselbalch and Gitte Knudsen (1. 5. 2008). „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. Архивирано из оригинала 3. 3. 2016. г. Приступљено 24. 7. 2011.
^ 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. doi:10.1111/j.1476-5381.1994.tb14064.x.
^ 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. PMC 2951497 . PMID 20812727. doi:10.1021/jm100668r.

Dodatna 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. PMID 7656980. S2CID 9015835. doi:10.1016/0014-5793(95)00828-W.
Blondel, O; Vandecasteele G; Gastineau M; et al. (1997). „Molecular and functional characterization of a 5-HT4 receptor cloned from human atrium.” (PDF). FEBS Lett. 412 (3): 465—74. PMID 9276448. S2CID 23714426. doi:10.1016/S0014-5793(97)00820-X. ^{[мртва веза]}
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. PMID 9349523. S2CID 25269904. doi:10.1046/j.1471-4159.1997.69051810.x.
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.” (PDF). NeuroReport. 8 (15): 3189—96. PMID 9351641. S2CID 20624532. doi:10.1097/00001756-199710200-00002.
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.” (PDF). J. Neurochem. 70 (6): 2252—61. PMID 9603189. S2CID 24203530. doi:10.1046/j.1471-4159.1998.70062252.x. Архивирано из оригинала (PDF) 10. 06. 2023. г. Приступљено 29. 07. 2023.
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. PMID 9724925. doi:10.3109/09687689809027521.
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. PMID 10646498. S2CID 33817190. doi:10.1046/j.1471-4159.2000.740478.x.
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. PMC 1571890 . PMID 10683202. doi:10.1038/sj.bjp.0703101.
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. PMID 11218067. S2CID 27504006. doi:10.1007/s002100000299.
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. PMID 11406291. doi:10.1016/S0169-328X(01)00095-X.
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. PMID 11716477. doi:10.1006/bbrc.2001.5979.
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. PMID 11750916. S2CID 23722311. doi:10.1016/S0028-3908(01)00154-X.
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. PMID 11989623. S2CID 23478175. doi:10.1023/A:1014895611874.
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. PMID 12399948. S2CID 21064320. doi:10.1038/sj.mp.4001133.
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. PMID 12446729. doi:10.1074/jbc.M206237200 .
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. PMC 139241 . PMID 12477932. doi:10.1073/pnas.242603899 .
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. PMID 12519861. S2CID 40285098. doi:10.1210/jc.2002-021107.
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. Bibcode:2003Sci...301..226M. PMID 12855812. S2CID 13641423. doi:10.1126/science.1084674.

Spoljašnje veze

„5-HT₄”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Архивирано из оригинала 05. 06. 2016. г. Приступљено 1. 7. 2018.

[pmid9371406-1] Claeysen S, Faye P, Sebben M, Lemaire S, Bockaert J, Dumuis A, Taviaux S (1997). „Assignment of 5-hydroxytryptamine receptor (HTR4) to human chromosome 5 bands q31→q33 by in situ hybridization.” (PDF). Cytogenet Cell Genet. 78 (2): 133—4. PMID 9371406. doi:10.1159/000134646.

[pmid9276448-2] Blondel O, Vandecasteele G, Gastineau M, Leclerc S, Dahmoune Y, Langlois M, Fischmeister R (1997). „Molecular and functional characterization of a 5-HT4 receptor cloned from human atrium.” (PDF). FEBS Lett. 412 (3): 465—74. PMID 9276448. S2CID 23714426. doi:10.1016/S0014-5793(97)00820-X. ^{[мртва веза]}

[entrez-3] „Entrez Gene: HTR4 5-hydroxytryptamine (serotonin) receptor 4”. Приступљено 1. 7. 2018.

[4] Hegde, SS; Eglen, RM (1. 10. 1996). „Peripheral 5-HT4 receptors”. The FASEB Journal. 10 (12): 1398—1407. PMID 8903510. S2CID 21596751. doi:10.1096/fasebj.10.12.8903510. Пронађени су сувишни параметри: |author= и |last1= (помоћ); Пронађени су сувишни параметри: |author2= и |last2= (помоћ)

[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 (4): 228—234. PMID 12888181. S2CID 27945284. doi:10.1016/S0924-977X(03)00009-9.

[6] Mnie-Filali, O.; Amraei, M. G.; Benmbarek, S.; Archer-Lahlou, E.; Peñas-Cazorla, R.; Vilaró, M. T.; Boye, S. M.; Piñeyro, G. (2010). „Serotonin 4 receptor (5-HT4R) internalization is isoform-specific: Effects of 5-HT and RS67333 on isoforms a and B”. Cellular Signalling. 22 (3): 501—509. PMID 19922792. doi:10.1016/j.cellsig.2009.11.004.

[pmid19168624-7] Pellissier LP, Sallander J, Campillo M, Gaven F, Queffeulou E, Pillot M, Dumuis A, Claeysen S, Bockaert J, Pardo L (2009). „Conformational toggle switches implicated in basal constitutive and agonist-induced activated states of 5-hydroxytryptamine-4 receptors” (PDF). Molecular Pharmacology. 75 (4): 982—90. PMID 19168624. S2CID 17957338. doi:10.1124/mol.108.053686.

[8] Kornum, B. R.; N. M. Lind; N. Gillings; Marner, Lisbeth; F. Andersen; Gitte Moos Knudsen (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—196. PMID 18797470. S2CID 16196384. doi:10.1038/jcbfm.2008.110.

[9] Lisbeth Marner, Nic Gillings, Roger Gunn, Robert Comley, William Baaré, Steen Hasselbalch and Gitte Knudsen (1. 5. 2008). „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. Архивирано из оригинала 3. 3. 2016. г. Приступљено 24. 7. 2011.

[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. doi:10.1111/j.1476-5381.1994.tb14064.x.

[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. PMC 2951497 . PMID 20812727. doi:10.1021/jm100668r.

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