Adenosine A2B receptor

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Adenosine A2b receptor
Identifiers
Symbols ADORA2B ; ADORA2
External IDs OMIM600446 MGI99403 HomoloGene20167 IUPHAR: A2B ChEMBL: 255 GeneCards: ADORA2B Gene
RNA expression pattern
PBB GE ADORA2B 205891 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 136 11541
Ensembl ENSG00000170425 ENSMUSG00000018500
UniProt P29275 Q60614
RefSeq (mRNA) NM_000676 NM_007413
RefSeq (protein) NP_000667 NP_031439
Location (UCSC) Chr 17:
15.85 – 15.88 Mb
Chr 11:
62.25 – 62.27 Mb
PubMed search [1] [2]

The adenosine A2B receptor, also known as ADORA2B, is a G-protein coupled adenosine receptor, and also denotes the human adenosine A2b receptor gene which encodes it.[1]

Mechanism

This integral membrane protein stimulates adenylate cyclase activity in the presence of adenosine. This protein also interacts with netrin-1, which is involved in axon elongation.

Gene

The gene is located near the Smith-Magenis syndrome region on chromosome 17.[1]

Ligands[edit]

Research into selective A2B ligands has lagged somewhat behind the development of ligands for the other three adenosine receptor subtypes, but a number of A2B-selective compounds have now been developed,[2][3][4][5][6][7][8][9][10][11] and research into their potential therapeutic applications is ongoing.[12][13][14][15][16][17]

Agonists[edit]

  • BAY 60-6583
  • NECA (N-ethylcarboxamidoadenosine)
  • (S)-PHPNECA - high affinity and efficacy at A2B, but poor selectivity over other adenosine receptor subtypes
  • LUF-5835
  • LUF-5845 - partial agonist

Antagonists and inverse agonists[edit]

  • Compound 38:[18] antagonist, high affinity and good subtype selectivity
  • ATL-801
  • CVT-6883
  • MRS-1706
  • MRS-1754
  • OSIP-339,391
  • PSB-603
  • PSB-0788
  • PSB-1115

References[edit]

  1. ^ a b "Entrez Gene: ADORA2B adenosine A2b receptor". 
  2. ^ Volpini R, Costanzi S, Lambertucci C, Taffi S, Vittori S, Klotz KN, Cristalli G (July 2002). "N(6)-alkyl-2-alkynyl derivatives of adenosine as potent and selective agonists at the human adenosine A(3) receptor and a starting point for searching A(2B) ligands". Journal of Medicinal Chemistry 45 (15): 3271–9. doi:10.1021/jm0109762. PMID 12109910. 
  3. ^ Volpini R, Costanzi S, Lambertucci C, Vittori S, Cristalli G (2002). "Purine nucleosides bearing 1-alkynyl chains as adenosine receptor agonists". Current Pharmaceutical Design 8 (26): 2285–98. doi:10.2174/1381612023392856. PMID 12369946. 
  4. ^ Baraldi PG, Tabrizi MA, Preti D, Bovero A, Romagnoli R, Fruttarolo F, Zaid NA, Moorman AR, Varani K, Gessi S, Merighi S, Borea PA (March 2004). "Design, synthesis, and biological evaluation of new 8-heterocyclic xanthine derivatives as highly potent and selective human A2B adenosine receptor antagonists". Journal of Medicinal Chemistry 47 (6): 1434–47. doi:10.1021/jm0309654. PMID 14998332. 
  5. ^ Cacciari B, Pastorin G, Bolcato C, Spalluto G, Bacilieri M, Moro S (December 2005). "A2B adenosine receptor antagonists: recent developments". Mini Reviews in Medicinal Chemistry 5 (12): 1053–60. doi:10.2174/138955705774933374. PMID 16375751. 
  6. ^ Baraldi PG, Romagnoli R, Preti D, Fruttarolo F, Carrion MD, Tabrizi MA (2006). "Ligands for A2B adenosine receptor subtype". Current Medicinal Chemistry 13 (28): 3467–82. doi:10.2174/092986706779010306. PMID 17168717. 
  7. ^ Beukers MW, Meurs I, Ijzerman AP (September 2006). "Structure-affinity relationships of adenosine A2B receptor ligands". Medicinal Research Reviews 26 (5): 667–98. doi:10.1002/med.20069. PMID 16847822. 
  8. ^ Elzein E, Kalla R, Li X, Perry T, Parkhill E, Palle V, Varkhedkar V, Gimbel A, Zeng D, Lustig D, Leung K, Zablocki J (January 2006). "Novel 1,3-dipropyl-8-(1-heteroarylmethyl-1H-pyrazol-4-yl)-xanthine derivatives as high affinity and selective A2B adenosine receptor antagonists". Bioorganic & Medicinal Chemistry Letters 16 (2): 302–6. doi:10.1016/j.bmcl.2005.10.002. PMID 16275090. 
  9. ^ Carotti A, Cadavid MI, Centeno NB, Esteve C, Loza MI, Martinez A, Nieto R, Raviña E, Sanz F, Segarra V, Sotelo E, Stefanachi A, Vidal B (January 2006). "Design, synthesis, and structure-activity relationships of 1-,3-,8-, and 9-substituted-9-deazaxanthines at the human A2B adenosine receptor". Journal of Medicinal Chemistry 49 (1): 282–99. doi:10.1021/jm0506221. PMID 16392813. 
  10. ^ Tabrizi MA, Baraldi PG, Preti D, Romagnoli R, Saponaro G, Baraldi S, Moorman AR, Zaid AN, Varani K, Borea PA (March 2008). "1,3-Dipropyl-8-(1-phenylacetamide-1H-pyrazol-3-yl)-xanthine derivatives as highly potent and selective human A(2B) adenosine receptor antagonists". Bioorganic & Medicinal Chemistry 16 (5): 2419–30. doi:10.1016/j.bmc.2007.11.058. PMID 18077171. 
  11. ^ Stefanachi A, Brea JM, Cadavid MI, Centeno NB, Esteve C, Loza MI, Martinez A, Nieto R, Raviña E, Sanz F, Segarra V, Sotelo E, Vidal B, Carotti A (March 2008). "1-, 3- and 8-substituted-9-deazaxanthines as potent and selective antagonists at the human A2B adenosine receptor". Bioorganic & Medicinal Chemistry 16 (6): 2852–69. doi:10.1016/j.bmc.2008.01.002. PMID 18226909. 
  12. ^ Volpini R, Costanzi S, Vittori S, Cristalli G, Klotz KN (2003). "Medicinal chemistry and pharmacology of A2B adenosine receptors". Current Topics in Medicinal Chemistry 3 (4): 427–43. doi:10.2174/1568026033392264. PMID 12570760. 
  13. ^ 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. 
  14. ^ Kolachala V, Ruble B, Vijay-Kumar M, Wang L, Mwangi S, Figler H, Figler R, Srinivasan S, Gewirtz A, Linden J, Merlin D, Sitaraman S (September 2008). "Blockade of adenosine A2B receptors ameliorates murine colitis". British Journal of Pharmacology 155 (1): 127–37. doi:10.1038/bjp.2008.227. PMC 2440087. PMID 18536750. 
  15. ^ Haskó G, Linden J, Cronstein B, Pacher P (September 2008). "Adenosine receptors: therapeutic aspects for inflammatory and immune diseases". Nature Reviews Drug Discovery 7 (9): 759–70. doi:10.1038/nrd2638. PMC 2568887. PMID 18758473. 
  16. ^ Ham J, Rees DA (December 2008). "The adenosine a2b receptor: its role in inflammation". Endocrine, Metabolic & Immune Disorders Drug Targets 8 (4): 244–54. doi:10.2174/187153008786848303. PMID 19075778. 
  17. ^ Kim MO, Kim MH, Lee SH, Suh HN, Lee YJ, Lee MY, Han HJ (June 2009). "5'-N-ethylcarboxamide induces IL-6 expression via MAPKs and NF-kappaB activation through Akt, Ca(2+)/PKC, cAMP signaling pathways in mouse embryonic stem cells". Journal of Cellular Physiology 219 (3): 752–9. doi:10.1002/jcp.21721. PMID 19194991. 
  18. ^ Stefanachi A, Nicolotti O, Leonetti F, et al. (2008). "1,3-Dialkyl-8-(hetero)aryl-9-OH-9-deazaxanthines as potent A(2B) adenosine receptor antagonists: Design, synthesis, structure-affinity and structure-selectivity relationships". Bioorganic & Medicinal Chemistry 16 (22): 9780–9. doi:10.1016/j.bmc.2008.09.067. PMID 18938084. 

External links[edit]

  • "Adenosine Receptors: A2B". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. 

Further reading[edit]