5-HT5A receptor
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
уредиProtein 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
уредиNeurotransmiter serotonin (5-hidroksitriptamin, 5-HT) uzima učešće u velikom broju psihijatrijskih stanja, kao i u vazokonstriktivnim i vazodilatornim efektima.[1]
Selektivni Ligandi
уредиMali 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
уреди
- Valerenska kiselina, komponenta valerijana, deluje kao 5HT5A parcijalni agonist.[8]
- DE19900637A1, selektivni ligand, Ki = 124 nM.[9]
Antagonisti
уреди- Latrepirdin (nije selektivan)[10]
- SB-699,551
Vidi još
уредиРеференце
уреди- ^ а б в „Entrez Gene: HTR5A 5-hydroxytryptamine (serotonin) receptor 5A”.
- ^ Rees S, den Daas I, Foord S, Goodson S, Bull D, Kilpatrick G, Lee M (1994). „Cloning and characterisation of the human 5-HT5A serotonin receptor”. FEBS Lett. 355 (3): 242—6. PMID 7988681. doi:10.1016/0014-5793(94)01209-1.
- ^ Francken BJ, Jurzak M, Vanhauwe JF, Luyten WH, Leysen JE (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. PMID 9865521. doi:10.1016/S0014-2999(98)00744-4.
- ^ Matthes H, Boschert U, Amlaiky N, Grailhe R, Plassat JL, Muscatelli F, Mattei MG, Hen R (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. Архивирано из оригинала 02. 12. 2008. г. Приступљено 24. 07. 2011.
- ^ Nelson, DL (2004). „5-HT5 receptors”. Curr Drug Targets CNS Neurol Disord. 3 (1): 53—8. PMID 14965244. doi:10.2174/1568007043482606.
- ^ Wesołowska A (2002). „In the search for selective ligands of 5-HT5, 5-HT6 and 5-HT7 serotonin receptors” (PDF). Pol J Pharmacol. 54 (4): 327—41. PMID 12523486.
- ^ Peters JU, Lübbers T, Alanine A, Kolczewski S, Blasco F, Steward L (2008). „Cyclic guanidines as dual 5-HT5A/5-HT7 receptor ligands: optimising brain penetration”. Bioorg. Med. Chem. Lett. 18 (1): 262—6. PMID 18023344. doi:10.1016/j.bmcl.2007.10.078.
- ^ 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. PMID 15921820. doi:10.1016/j.molbrainres.2005.04.009.
- ^ Garcia-Ladona, Francisco Javier; Szabo, Laszlo; Steiner, Gerd; Hofmann, Hans-Peter (15. 06. 2004). „Use of 5-HT5-ligands in the treatment of neurodegenerative and neuropsychiatric disturbances”. patent-number 6750221.
- ^ Wu J, Li Q, Bezprozvanny I (2008). „Evaluation of Dimebon in cellular model of Huntington's disease”. Mol Neurodegener. 3 (1): 15. PMC 2577671
. PMID 18939977. doi:10.1186/1750-1326-3-15.
Dodatna literatura
уреди- Raymond, JR; YV, Mukhin; Gelasco A; et al. (2002). „Multiplicity of mechanisms of serotonin receptor signal transduction.”. Pharmacol. Ther. 92 (2-3): 179—212. PMID 11916537. doi:10.1016/S0163-7258(01)00169-3.
- Thomas, DR (2006). „5-ht5A receptors as a therapeutic target.”. Pharmacol. Ther. 111 (3): 707—14. PMID 16516972. doi:10.1016/j.pharmthera.2005.12.006.
- 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. PMID 7988681. doi:10.1016/0014-5793(94)01209-1.
- 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. PMID 8978771. doi:10.1159/000134184.
- „Toward a complete human genome sequence.”. Genome Res. 8 (11): 1097—108. 1999. PMID 9847074. doi:10.1101/gr.8.11.1097.
- 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. PMID 11287788. doi:10.1159/000054878.
- 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. PMID 11317225. doi:10.1038/sj.mp.4000829.
- 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. PMID 11343685. doi:10.1016/S0014-2999(01)00933-5.
- Strausberg, RL; EA, Feingold; 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.
- 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. PMID 12558985. doi:10.1046/j.1471-4159.2003.01518.x.
- Scherer, SW; Cheung J; MacDonald, JR; et al. (2003). „Human chromosome 7: DNA sequence and biology.”. Science. 300 (5620): 767—72. PMC 2882961 . PMID 12690205. doi:10.1126/science.1083423.
- Hillier, LW; RS, Fulton; Fulton, LA; et al. (2003). „The DNA sequence of human chromosome 7.”. Nature. 424 (6945): 157—64. PMID 12853948. doi:10.1038/nature01782.
- 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. PMID 12930153. doi:10.1021/jm030080s.
- 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. PMID 14702039. doi:10.1038/ng1285.
- 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. PMC 528928 . PMID 15489334. doi:10.1101/gr.2596504.
- 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. PMID 15921820. doi:10.1016/j.molbrainres.2005.04.009.