5-HT5A receptor
(Preusmjereno sa stranice 5-HT5A)
| edit |
5-HT5A (5-hidroksitriptaminski (serotoninski) receptor 5A, HTR5A) je protein koji je kod ljudi kodiran HTR5A genom.[1][2]
| 5-hidroksitriptaminski (serotoninski) receptor 5A | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Identifikatori | |||||||||||
| Simboli | HTR5A; 5-HT5A; MGC138226 | ||||||||||
| Vanjski ID | OMIM: 601305 MGI: 96283 HomoloGene: 22461 IUPHAR: 5-ht5a GeneCards: HTR5A Gene | ||||||||||
| |||||||||||
| Pregled RNK izražavanja | |||||||||||
 | |||||||||||
| podaci | |||||||||||
| Ortolozi | |||||||||||
| Vrsta | Čovek | Miš | |||||||||
| Entrez | 3361 | 15563 | |||||||||
| Ensembl | ENSG00000157219 | ENSMUSG00000039106 | |||||||||
| UniProt | P47898 | Q3URB0 | |||||||||
| RefSeq (mRNA) | NM_024012 | NM_008314 | |||||||||
| RefSeq (protein) | NP_076917 | NP_032340 | |||||||||
| Lokacija (UCSC) | Chr 7: 154.49 - 154.51 Mb | Chr 5: 28.17 - 28.19 Mb | |||||||||
| PubMed pretraga | [1] | [2] | |||||||||
Funkcija uredi
Protein kodiran 5-HT5A genom je član familije 5-hidroksitriptaminskih receptora. Njegov endogeni ligand je 5-hidroksitriptamin. On snižava cAMP nivoe putem Gi i Go proteina.[3] Za ovaj protein je pokazano da delom funkcioniše putem regulacije intracelularne mobilizacije Ca2+.[1]
Glodari imaju dva funkcionalna tipa 5-HT5 receptora, 5-HT5A i 5-HT5B,[4] Ljudi takože imaju 5-HT5B gen, ali njegova kodirajuća sekvenca sadrži stop kodone, tako da taj gen nije funkcionalan, i samo je 5-HT5A izražen u ljudskom mozgu.[5]
Klinički značaj uredi
Neurotransmiter serotonin (5-hidroksitriptamin, 5-HT) uzima učešće u velikom broju psihijatrijskih stanja, kao i u vazokonstriktivnim i vazodilatornim efektima.[1]
Selektivni Ligandi uredi
Mali broj visoko selektivnih liganda je komercijalno dostupan za 5-HT5A receptor. Selektivna aktivacija ovog receptora se može ostvariti korištenjem neselektivnog agonista serotoninskog receptor 5-karboksamidotriptamina u kombinaciji sa selektivnim antagonistima za druge ciljeve (primarno 5-HT1A, 5-HT1B, 5-HT1D i 5-HT7).[6][7]
Agonisti uredi
- Valerenska kiselina, komponenta valerijana, deluje kao 5HT5A parcijalni agonist.[8]
- DE19900637A1, selektivni ligand, Ki = 124 nM.[9]
Antagonisti uredi
- Latrepirdin (nije selektivan)[10]
- SB-699,551
Vidi još uredi
Reference uredi
- ↑ 1,0 1,1 1,2 „Entrez Gene: HTR5A 5-hydroxytryptamine (serotonin) receptor 5A”.
- ↑ Rees S, den Daas I, Foord S, Goodson S, Bull D, Kilpatrick G, Lee M (December 1994). „Cloning and characterisation of the human 5-HT5A serotonin receptor”. FEBS Lett. 355 (3): 242–6. DOI:10.1016/0014-5793(94)01209-1. PMID 7988681.
- ↑ Francken BJ, Jurzak M, Vanhauwe JF, Luyten WH, Leysen JE (November 1998). „The human 5-ht5A receptor couples to Gi/Go proteins and inhibits adenylate cyclase in HEK 293 cells”. Eur. J. Pharmacol. 361 (2-3): 299–309. DOI:10.1016/S0014-2999(98)00744-4. PMID 9865521.
- ↑ Matthes H, Boschert U, Amlaiky N, Grailhe R, Plassat JL, Muscatelli F, Mattei MG, Hen R (March 1993). „Mouse 5-hydroxytryptamine5A and 5-hydroxytryptamine5B receptors define a new family of serotonin receptors: cloning, functional expression, and chromosomal localization”. Mol. Pharmacol. 43 (3): 313–9. PMID 8450829. Arhivirano iz originala na datum 2008-12-02. Pristupljeno 2014-05-02.
- ↑ Nelson DL (February 2004). „5-HT5 receptors”. Curr Drug Targets CNS Neurol Disord 3 (1): 53–8. DOI:10.2174/1568007043482606. PMID 14965244.
- ↑ Wesołowska A (2002). „In the search for selective ligands of 5-HT5, 5-HT6 and 5-HT7 serotonin receptors”. Pol J Pharmacol 54 (4): 327–41. PMID 12523486.
- ↑ Peters JU, Lübbers T, Alanine A, Kolczewski S, Blasco F, Steward L (January 2008). „Cyclic guanidines as dual 5-HT5A/5-HT7 receptor ligands: optimising brain penetration”. Bioorg. Med. Chem. Lett. 18 (1): 262–6. DOI:10.1016/j.bmcl.2007.10.078. PMID 18023344.
- ↑ Dietz BM, Mahady GB, Pauli GF, Farnsworth NR (August 2005). „Valerian extract and valerenic acid are partial agonists of the 5-HT5a receptor in vitro”. Brain Res. Mol. Brain Res. 138 (2): 191–7. DOI:10.1016/j.molbrainres.2005.04.009. PMID 15921820.
- ↑ Garcia-Ladona Francisco Javier, Szabo Laszlo, Steiner Gerd, Hofmann Hans-Peter (2004-06-15). US patent 6750221, Use of 5-HT5-ligands in the treatment of neurodegenerative and neuropsychiatric disturbances
- ↑ Wu J, Li Q, Bezprozvanny I (2008). „Evaluation of Dimebon in cellular model of Huntington's disease”. Mol Neurodegener 3 (1): 15. DOI:10.1186/1750-1326-3-15. PMC 2577671. PMID 18939977.
Literatura uredi
- Raymond JR, Mukhin YV, Gelasco A, et al. (2002). „Multiplicity of mechanisms of serotonin receptor signal transduction.”. Pharmacol. Ther. 92 (2-3): 179–212. DOI:10.1016/S0163-7258(01)00169-3. PMID 11916537.
- Thomas DR (2006). „5-ht5A receptors as a therapeutic target.”. Pharmacol. Ther. 111 (3): 707–14. DOI:10.1016/j.pharmthera.2005.12.006. PMID 16516972.
- Rees S, den Daas I, Foord S, et al. (1995). „Cloning and characterisation of the human 5-HT5A serotonin receptor.”. FEBS Lett. 355 (3): 242–6. DOI:10.1016/0014-5793(94)01209-1. PMID 7988681.
- Schanen NC, Scherer SW, Tsui LC, Francke U (1997). „Assignment of the 5-hydroxytryptamine (serotonin) receptor 5A gene (HTR5A) to human chromosome band 7q36.1.”. Cytogenet. Cell Genet. 72 (2-3): 187–8. DOI:10.1159/000134184. PMID 8978771.
- „Toward a complete human genome sequence.”. Genome Res. 8 (11): 1097–108. 1999. DOI:10.1101/gr.8.11.1097. PMID 9847074.
- Francken BJ, Josson K, Lijnen P, et al. (2000). „Human 5-hydroxytryptamine(5A) receptors activate coexpressed G(i) and G(o) proteins in Spodoptera frugiperda 9 cells.”. Mol. Pharmacol. 57 (5): 1034–44. PMID 10779389.
- Marazziti D, Ori M, Nardini M, et al. (2001). „mRNA expression of serotonin receptors of type 2C and 5A in human resting lymphocytes.”. Neuropsychobiology 43 (3): 123–6. DOI:10.1159/000054878. PMID 11287788.
- Iwata N, Ozaki N, Inada T, Goldman D (2001). „Association of a 5-HT(5A) receptor polymorphism, Pro15Ser, to schizophrenia.”. Mol. Psychiatry 6 (2): 217–9. DOI:10.1038/sj.mp.4000829. PMID 11317225.
- Grailhe R, Grabtree GW, Hen R (2001). „Human 5-HT(5) receptors: the 5-HT(5A) receptor is functional but the 5-HT(5B) receptor was lost during mammalian evolution.”. Eur. J. Pharmacol. 418 (3): 157–67. DOI:10.1016/S0014-2999(01)00933-5. PMID 11343685.
- 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.
- Noda M, Yasuda S, Okada M, et al. (2003). „Recombinant human serotonin 5A receptors stably expressed in C6 glioma cells couple to multiple signal transduction pathways.”. J. Neurochem. 84 (2): 222–32. DOI:10.1046/j.1471-4159.2003.01518.x. PMID 12558985.
- Scherer SW, Cheung J, MacDonald JR, et al. (2003). „Human chromosome 7: DNA sequence and biology.”. Science 300 (5620): 767–72. DOI:10.1126/science.1083423. PMC 2882961. PMID 12690205.
- Hillier LW, Fulton RS, Fulton LA, et al. (2003). „The DNA sequence of human chromosome 7.”. Nature 424 (6945): 157–64. DOI:10.1038/nature01782. PMID 12853948.
- Khorana N, Smith C, Herrick-Davis K, et al. (2003). „Binding of tetrahydrocarboline derivatives at human 5-HT5A receptors.”. J. Med. Chem. 46 (18): 3930–7. DOI:10.1021/jm030080s. PMID 12930153.
- Ota T, Suzuki Y, Nishikawa T, et al. (2004). „Complete sequencing and characterization of 21,243 full-length human cDNAs.”. Nat. Genet. 36 (1): 40–5. DOI:10.1038/ng1285. PMID 14702039.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). „The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”. Genome Res. 14 (10B): 2121–7. DOI:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Dietz BM, Mahady GB, Pauli GF, Farnsworth NR (2005). „Valerian extract and valerenic acid are partial agonists of the 5-HT5a receptor in vitro.”. Brain Res. Mol. Brain Res. 138 (2): 191–7. DOI:10.1016/j.molbrainres.2005.04.009. PMID 15921820.