5-HT5A receptor

Из Википедије, слободне енциклопедије
5-hidroksitriptaminski (serotoninski) receptor 5A
Identifikatori
Simboli HTR5A; 5-HT5A; MGC138226
Vanjski ID OMIM601305 MGI96283 HomoloGene22461 IUPHAR: 5-ht5a GeneCards: HTR5A Gene
Pregled RNK izražavanja
PBB GE HTR5A 221362 at tn.png
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]

5-HT5A (5-hidroksitriptaminski (serotoninski) receptor 5A, HTR5A) je protein koji je kod ljudi kodiran HTR5A genom.[1][2]

Funkcija[уреди]

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[уреди]

Neurotransmiter serotonin (5-hidroksitriptamin, 5-HT) uzima učešće u velikom broju psihijatrijskih stanja, kao i u vazokonstriktivnim i vazodilatornim efektima.[1]

Selektivni Ligandi[уреди]

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[уреди]

DE19900637A1
  • DE19900637A1, selektivni ligand, Ki = 124 nM.[9]

Antagonisti[уреди]

Vidi još[уреди]

Literatura[уреди]

  1. 1,0 1,1 1,2 „Entrez Gene: HTR5A 5-hydroxytryptamine (serotonin) receptor 5A”. 
  2. 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. doi:10.1016/0014-5793(94)01209-1. PMID 7988681. 
  3. 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. doi:10.1016/S0014-2999(98)00744-4. PMID 9865521. 
  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. 
  5. Nelson DL (2004). „5-HT5 receptors”. Curr Drug Targets CNS Neurol Disord. 3 (1): 53—8. doi:10.2174/1568007043482606. PMID 14965244. 
  6. 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. 
  7. 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. doi:10.1016/j.bmcl.2007.10.078. PMID 18023344. 
  8. 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. 
  9. „Use of 5-HT5-ligands in the treatment of neurodegenerative and neuropsychiatric disturbances”. 15. 06. 2004. 
  10. 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 2577671слободно за читање. PMID 18939977. 

Dodatna literatura[уреди]

  • 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 139241слободно за читање. 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 2882961слободно за читање. 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 528928слободно за читање. 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. 

Spoljašnje veze[уреди]

  • „5-ht5a. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.