The adenosine A2B receptor, also known as ADORA2B, is a G-protein coupledadenosine receptor, and also denotes the human adenosine A2b receptor gene which encodes it.[1]
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
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]
↑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. PMID12109910.
↑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. PMID16847822.
↑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. PMID16275090.
↑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. PMID16392813.
↑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. PMID18077171.
↑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. PMID18226909.
↑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. PMID19194991.
↑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. PMID18938084.
Jacobson MA, Johnson RG, Luneau CJ, Salvatore CA (1995). "Cloning and chromosomal localization of the human A2b adenosine receptor gene (ADORA2B) and its pseudogene". Genomics. 27 (2): 374–6. doi:10.1006/geno.1995.1061. PMID7558011.
Townsend-Nicholson A, Baker E, Sutherland GR, Schofield PR (1995). "Localization of the adenosine A2b receptor subtype gene (ADORA2B) to chromosome 17p11.2-p12 by FISH and PCR screening of somatic cell hybrids". Genomics. 25 (2): 605–7. doi:10.1016/0888-7543(95)80074-V. PMID7790006.
Strohmeier GR, Reppert SM, Lencer WI, Madara JL (1995). "The A2b adenosine receptor mediates cAMP responses to adenosine receptor agonists in human intestinal epithelia". J. Biol. Chem. 270 (5): 2387–94. doi:10.1074/jbc.270.5.2387. PMID7836474.
Feoktistov I, Murray JJ, Biaggioni I (1994). "Positive modulation of intracellular Ca2+ levels by adenosine A2b receptors, prostacyclin, and prostaglandin E1 via a cholera toxin-sensitive mechanism in human erythroleukemia cells". Mol. Pharmacol. 45 (6): 1160–7. PMID8022409.
Mirabet M, Herrera C, Cordero OJ, et al. (1999). "Expression of A2B adenosine receptors in human lymphocytes: their role in T cell activation". J. Cell Sci. 112 (4): 491–502. PMID9914161.
Feoktistov I, Goldstein AE, Biaggioni I (1999). "Role of p38 mitogen-activated protein kinase and extracellular signal-regulated protein kinase kinase in adenosine A2B receptor-mediated interleukin-8 production in human mast cells". Mol. Pharmacol. 55 (4): 726–34. PMID10101031.
Corset V, Nguyen-Ba-Charvet KT, Forcet C, et al. (2000). "Netrin-1-mediated axon outgrowth and cAMP production requires interaction with adenosine A2b receptor". Nature. 407 (6805): 747–50. doi:10.1038/35037600. PMID11048721.
Herrera C, Casadó V, Ciruela F, et al. (2001). "Adenosine A2B receptors behave as an alternative anchoring protein for cell surface adenosine deaminase in lymphocytes and cultured cells". Mol. Pharmacol. 59 (1): 127–34. PMID11125033.
Christofi FL, Zhang H, Yu JG, et al. (2001). "Differential gene expression of adenosine A1, A2a, A2b, and A3 receptors in the human enteric nervous system". J. Comp. Neurol. 439 (1): 46–64. doi:10.1002/cne.1334. PMID11579381.
Hayallah AM, Sandoval-Ramírez J, Reith U, et al. (2002). "1,8-disubstituted xanthine derivatives: synthesis of potent A2B-selective adenosine receptor antagonists". J. Med. Chem. 45 (7): 1500–10. doi:10.1021/jm011049y. PMID11906291.
Sitaraman SV, Wang L, Wong M, et al. (2002). "The adenosine 2b receptor is recruited to the plasma membrane and associates with E3KARP and Ezrin upon agonist stimulation". J. Biol. Chem. 277 (36): 33188–95. doi:10.1074/jbc.M202522200. PMID12080047.
Ryzhov S, Goldstein AE, Matafonov A, et al. (2004). "Adenosine-activated mast cells induce IgE synthesis by B lymphocytes: an A2B-mediated process involving Th2 cytokines IL-4 and IL-13 with implications for asthma". J. Immunol. 172 (12): 7726–33. doi:10.4049/jimmunol.172.12.7726. PMID15187156.
Kolachala V, Asamoah V, Wang L, et al. (2005). "Interferon-gamma down-regulates adenosine 2b receptor-mediated signaling and short circuit current in the intestinal epithelia by inhibiting the expression of adenylate cyclase". J. Biol. Chem. 280 (6): 4048–57. doi:10.1074/jbc.M409577200. PMID15550390.
External links
"Adenosine Receptors: A2B". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.