Adenozinski A3 receptor

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Adenozinski A3 receptor
Identifikatori
Simboli ADORA3; A3AR; AD026; RP11-552M11.7; bA552M11.5
Vanjski ID OMIM600445 MGI104847 HomoloGene550 IUPHAR: A3 GeneCards: ADORA3 Gene
Pregled RNK izražavanja
PBB GE ADORA3 206171 at tn.png
podaci
Ortolozi
Vrsta Čovek Miš
Entrez 140 11542
Ensembl ENSG00000121933 ENSMUSG00000000562
UniProt P33765 Q3U4C5
RefSeq (mRNA) NM_000677 NM_009631
RefSeq (protein) NP_000668 NP_033761
Lokacija (UCSC) Chr 1:
111.83 - 111.91 Mb
Chr 3:
106.03 - 106.04 Mb
PubMed pretraga [1] [2]

Adenozinski A3 receptor (ADORA3) je adenozinski receptor. On je kodiran humanim ADORA3 genom.

Funkcija[uredi - уреди]

Adenozinski A3 receptori je G protein-spregnuti receptor koji učestvuje u mnogobrojnim ćelijskim signalnim putevima i fiziološkim funkcijama. On posreduje kontinuirane kardioprotektivne funkcije tokom srčane ishemije, i učestvuje u inhibiciji neutrofilne degranulacije kod neutrofilima-posredovane povrede tkiva. Smatra se da ima neurozaštitno ali i neurodegenerativno dejstvo.

Gen[uredi - уреди]

Višestruke transkriptne varijante koje kodiraju različite izoforme su poznate za ovaj gen.[1]

Terapeutske implikacije[uredi - уреди]

Agonist adenozinskog A3 receptora (CF-101) je u kliničkim ispitivanjima za lečenje reumatoidnog artritisa.[2]

Selektivni ligandi[uredi - уреди]

Brojni selektivni A3 ligandi su dostupni.[3][4][5][6][7][8][9][10][11][12][13][14]

Agonisti/Pozitivni alosterni modulatori

  • 2-(1-Heksinil)-N-metiladenozin
  • CF-101 (IB-MECA)
  • CF-102
  • 2-Cl-IB-MECA
  • CP-532,903
  • LUF-6000
  • MRS-3558

Antagonisti/Negativni alosterini modulatori

  • KF-26777
  • MRS-545
  • MRS-1191
  • MRS-1220
  • MRS-1334
  • MRS-1523
  • MRS-3777
  • MRE-3005-F20
  • MRE-3008-F20
  • PSB-11
  • OT-7999
  • VUF-5574

Inverzni agonisti

Literatura[uredi - уреди]

  1. "Entrez Gene: ADORA3 adenosine A3 receptor". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=140. 
  2. Silverman MH, Strand V, Markovits D, Nahir M, Reitblat T, Molad Y, Rosner I, Rozenbaum M, Mader R, Adawi M, Caspi D, Tishler M, Langevitz P, Rubinow A, Friedman J, Green L, Tanay A, Ochaion A, Cohen S, Kerns WD, Cohn I, Fishman-Furman S, Farbstein M, Yehuda SB, Fishman P (January 2008). "Clinical evidence for utilization of the A3 adenosine receptor as a target to treat rheumatoid arthritis: data from a phase II clinical trial". J. Rheumatol. 35 (1): 41–8. PMID 18050382. 
  3. Kim SK, Gao ZG, Jeong LS, Jacobson KA (December 2006). "Docking studies of agonists and antagonists suggest an activation pathway of the A3 adenosine receptor". Journal of Molecular Graphics & Modelling 25 (4): 562–77. doi:10.1016/j.jmgm.2006.05.004. PMID 16793299. 
  4. Ge ZD, Peart JN, Kreckler LM, Wan TC, Jacobson MA, Gross GJ, Auchampach JA (December 2006). "Cl-IB-MECA [2-chloro-N6-(3-iodobenzyl)adenosine-5'-N-methylcarboxamide] reduces ischemia/reperfusion injury in mice by activating the A3 adenosine receptor". The Journal of Pharmacology and Experimental Therapeutics 319 (3): 1200–10. doi:10.1124/jpet.106.111351. PMC 2430759. PMID 16985166. 
  5. Jeong LS, Lee HW, Jacobson KA, Lee SK, Chun MW (2005). "Development of potent and selective human A3 adenosine receptor agonists". Nucleic Acids Symposium Series (2004) 49 (49): 31–2. doi:10.1093/nass/49.1.31. PMID 17150618. 
  6. Bevan N, Butchers PR, Cousins R, Coates J, Edgar EV, Morrison V, Sheehan MJ, Reeves J, Wilson DJ (June 2007). "Pharmacological characterisation and inhibitory effects of (2R,3R,4S,5R)-2-(6-amino-2[(1S)-2-hydroxy-1-(phenylmethyl)ethyl]amino9H-purin-9-yl)-5-(2-ethyl-2H-tetrazol-5-yl)tetrahydro-3,4-furandiol, a novel ligand that demonstrates both adenosine A(2A) receptor agonist and adenosine A(3) receptor antagonist activity". European Journal of Pharmacology 564 (1-3): 219–25. doi:10.1016/j.ejphar.2007.01.094. PMID 17382926. 
  7. Gao ZG, Jacobson KA (September 2007). "Emerging adenosine receptor agonists". Expert Opinion on Emerging Drugs 12 (3): 479–92. doi:10.1517/14728214.12.3.479. PMID 17874974. 
  8. Wan TC, Ge ZD, Tampo A, Mio Y, Bienengraeber MW, Tracey WR, Gross GJ, Kwok WM, Auchampach JA (January 2008). "The A3 adenosine receptor agonist CP-532,903 [N6-(2,5-dichlorobenzyl)-3'-aminoadenosine-5'-N-methylcarboxamide] protects against myocardial ischemia/reperfusion injury via the sarcolemmal ATP-sensitive potassium channel". J. Pharmacol. Exp. Ther. 324 (1): 234–43. doi:10.1124/jpet.107.127480. PMC 2435594. PMID 17906066. 
  9. Cordeaux Y, Briddon SJ, Alexander SP, Kellam B, Hill SJ (March 2008). "Agonist-occupied A3 adenosine receptors exist within heterogeneous complexes in membrane microdomains of individual living cells". The FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology 22 (3): 850–60. doi:10.1096/fj.07-8180com. PMID 17959910. 
  10. Priego EM, Pérez-Pérez MJ, von Frijtag Drabbe Kuenzel JK, de Vries H, Ijzerman AP, Camarasa MJ, Martín-Santamaría S (January 2008). "Selective human adenosine A3 antagonists based on pyrido[2,1-f]purine-2,4-diones: novel features of hA3 antagonist binding". ChemMedChem 3 (1): 111–9. doi:10.1002/cmdc.200700173. PMID 18000937. 
  11. Jeong LS, Lee HW, Kim HO, Tosh DK, Pal S, Choi WJ, Gao ZG, Patel AR, Williams W, Jacobson KA, Kim HD (March 2008). "Structure-activity relationships of 2-chloro-N6-substituted-4'-thioadenosine-5'-N,N-dialkyluronamides as human A3 adenosine receptor antagonists". Bioorganic & Medicinal Chemistry Letters 18 (5): 1612–6. doi:10.1016/j.bmcl.2008.01.070. PMID 18255292. 
  12. Gao ZG, Jacobson KA (April 2008). "Translocation of arrestin induced by human A(3) adenosine receptor ligands in an engineered cell line: comparison with G protein-dependent pathways". Pharmacological Research : the Official Journal of the Italian Pharmacological Society 57 (4): 303–11. doi:10.1016/j.phrs.2008.02.008. PMC 2409065. PMID 18424164. 
  13. Bar-Yehuda S, Stemmer SM, Madi L, Castel D, Ochaion A, Cohen S, Barer F, Zabutti A, Perez-Liz G, Del Valle L, Fishman P (August 2008). "The A3 adenosine receptor agonist CF102 induces apoptosis of hepatocellular carcinoma via de-regulation of the Wnt and NF-kappaB signal transduction pathways". International Journal of Oncology 33 (2): 287–95. PMID 18636149. 
  14. Gao ZG, Ye K, Göblyös A, Ijzerman AP, Jacobson KA (2008). "Flexible modulation of agonist efficacy at the human A3 adenosine receptor by the imidazoquinoline allosteric enhancer LUF6000". BMC Pharmacology 8: 20. doi:10.1186/1471-2210-8-20. PMC 2625337. PMID 19077268. 

Dodatna literatura[uredi - уреди]

Spoljašnje veze[uredi - уреди]