Biology:Adenosine A2B receptor
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Short description: Protein-coding gene in the species Homo sapiens
 Generic protein structure example |
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
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][18]
Agonists
- 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
- Compound 38:[19] antagonist, high affinity and good subtype selectivity
- ISAM-R56A:[18] non-xanthinic high affinity selective antagonist (Ki: 1.50 nM)
- ISAM-140:[20] non-xanthinic selective antagonist (Ki: 3.49 nM).
- ATL-801
- CVT-6883
- MRS-1706
- MRS-1754
- OSIP-339,391
- PSB-603: xanthinic antagonist
- PSB-0788: xanthinic antagonist
- PSB-1115: xanthinic antagonist
- PSB-1901:[21] xanthinic antagonist with picomolar potency
References
- ↑ 1.0 1.1 "Entrez Gene: ADORA2B adenosine A2b receptor". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=136.
- ↑ "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): 3271–3279. July 2002. doi:10.1021/jm0109762. PMID 12109910.
- ↑ "Purine nucleosides bearing 1-alkynyl chains as adenosine receptor agonists". Current Pharmaceutical Design 8 (26): 2285–2298. 2002. doi:10.2174/1381612023392856. PMID 12369946. http://www.bentham-direct.org/pages/content.php?CPD/2002/00000008/00000026/0002B.SGM.
- ↑ "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): 1434–1447. March 2004. doi:10.1021/jm0309654. PMID 14998332.
- ↑ "A2B adenosine receptor antagonists: recent developments". Mini Reviews in Medicinal Chemistry 5 (12): 1053–1060. December 2005. doi:10.2174/138955705774933374. PMID 16375751. http://www.bentham-direct.org/pages/content.php?MRMC/2005/00000005/00000012/0001N.SGM.
- ↑ "Ligands for A2B adenosine receptor subtype". Current Medicinal Chemistry 13 (28): 3467–3482. 2006. doi:10.2174/092986706779010306. PMID 17168717. http://www.bentham-direct.org/pages/content.php?CMC/2006/00000013/00000028/0008C.SGM.
- ↑ "Structure-affinity relationships of adenosine A2B receptor ligands". Medicinal Research Reviews 26 (5): 667–698. September 2006. doi:10.1002/med.20069. PMID 16847822.
- ↑ "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): 302–306. January 2006. doi:10.1016/j.bmcl.2005.10.002. PMID 16275090.
- ↑ "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): 282–299. January 2006. doi:10.1021/jm0506221. PMID 16392813.
- ↑ "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): 2419–2430. March 2008. doi:10.1016/j.bmc.2007.11.058. PMID 18077171.
- ↑ "1-, 3- and 8-substituted-9-deazaxanthines as potent and selective antagonists at the human A2B adenosine receptor". Bioorganic & Medicinal Chemistry 16 (6): 2852–2869. March 2008. doi:10.1016/j.bmc.2008.01.002. PMID 18226909.
- ↑ "Medicinal chemistry and pharmacology of A2B adenosine receptors". Current Topics in Medicinal Chemistry 3 (4): 427–443. 2003. doi:10.2174/1568026033392264. PMID 12570760. http://www.bentham-direct.org/pages/content.php?CTMC/2003/00000003/00000004/0007R.SGM.
- ↑ "Emerging adenosine receptor agonists". Expert Opinion on Emerging Drugs 12 (3): 479–492. September 2007. doi:10.1517/14728214.12.3.479. PMID 17874974. https://zenodo.org/record/1236313.
- ↑ "Blockade of adenosine A2B receptors ameliorates murine colitis". British Journal of Pharmacology 155 (1): 127–137. September 2008. doi:10.1038/bjp.2008.227. PMID 18536750.
- ↑ "Adenosine receptors: therapeutic aspects for inflammatory and immune diseases". Nature Reviews. Drug Discovery 7 (9): 759–770. September 2008. doi:10.1038/nrd2638. PMID 18758473.
- ↑ "The adenosine a2b receptor: its role in inflammation". Endocrine, Metabolic & Immune Disorders Drug Targets 8 (4): 244–254. December 2008. doi:10.2174/187153008786848303. PMID 19075778. http://www.bentham-direct.org/pages/content.php?EMIDDT/2008/00000008/00000004/0003V.SGM.
- ↑ "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): 752–759. June 2009. doi:10.1002/jcp.21721. PMID 19194991.
- ↑ 18.0 18.1 "A2B adenosine receptor antagonists rescue lymphocyte activity in adenosine-producing patient-derived cancer models". Journal for Immunotherapy of Cancer 10 (5): e004592. May 2022. doi:10.1136/jitc-2022-004592. PMID 35580926.
- ↑ "1,3-Dialkyl-8-(hetero)aryl-9-OH-9-deazaxanthines as potent A2B adenosine receptor antagonists: design, synthesis, structure-affinity and structure-selectivity relationships". Bioorganic & Medicinal Chemistry 16 (22): 9780–9789. November 2008. doi:10.1016/j.bmc.2008.09.067. PMID 18938084.
- ↑ "Discovery of Potent and Highly Selective A2B Adenosine Receptor Antagonist Chemotypes". Journal of Medicinal Chemistry 59 (5): 1967–1983. March 2016. doi:10.1021/acs.jmedchem.5b01586. PMID 26824742.
- ↑ "A2B Adenosine Receptor Antagonists with Picomolar Potency". Journal of Medicinal Chemistry 62 (8): 4032–4055. April 2019. doi:10.1021/acs.jmedchem.9b00071. PMID 30835463.
Further reading
- "Adenosine receptors". The Journal of Biological Chemistry 267 (10): 6451–6454. April 1992. doi:10.1016/S0021-9258(19)50445-8. PMID 1551861.
- "Molecular cloning and expression of an adenosine A2b receptor from human brain". Biochemical and Biophysical Research Communications 187 (1): 86–93. August 1992. doi:10.1016/S0006-291X(05)81462-7. PMID 1325798.
- "Inhibition of tPA-induced hemorrhagic transformation involves adenosine A2b receptor activation after cerebral ischemia". Neurobiology of Disease 108: 173–182. December 2017. doi:10.1016/j.nbd.2017.08.011. PMID 28830843.
- "Cloning and chromosomal localization of the human A2b adenosine receptor gene (ADORA2B) and its pseudogene". Genomics 27 (2): 374–376. May 1995. doi:10.1006/geno.1995.1061. PMID 7558011.
- "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): 605–607. January 1995. doi:10.1016/0888-7543(95)80074-V. PMID 7790006.
- "The A2b adenosine receptor mediates cAMP responses to adenosine receptor agonists in human intestinal epithelia". The Journal of Biological Chemistry 270 (5): 2387–2394. February 1995. doi:10.1074/jbc.270.5.2387. PMID 7836474.
- "Positive modulation of intracellular Ca2+ levels by adenosine A2b receptors, prostacyclin, and prostaglandin E1 via a cholera toxin-sensitive mechanism in human erythroleukemia cells". Molecular Pharmacology 45 (6): 1160–1167. June 1994. PMID 8022409.
- "Expression of A2B adenosine receptors in human lymphocytes: their role in T cell activation". Journal of Cell Science 112 ( Pt 4) (4): 491–502. February 1999. doi:10.1242/jcs.112.4.491. PMID 9914161.
- "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". Molecular Pharmacology 55 (4): 726–734. April 1999. PMID 10101031.
- "Netrin-1-mediated axon outgrowth and cAMP production requires interaction with adenosine A2b receptor". Nature 407 (6805): 747–750. October 2000. doi:10.1038/35037600. PMID 11048721. Bibcode: 2000Natur.407..747C.
- "Adenosine A2B receptors behave as an alternative anchoring protein for cell surface adenosine deaminase in lymphocytes and cultured cells". Molecular Pharmacology 59 (1): 127–134. January 2001. doi:10.1124/mol.59.1.127. PMID 11125033.
- "Differential gene expression of adenosine A1, A2a, A2b, and A3 receptors in the human enteric nervous system". The Journal of Comparative Neurology 439 (1): 46–64. October 2001. doi:10.1002/cne.1334. PMID 11579381.
- "1,8-disubstituted xanthine derivatives: synthesis of potent A2B-selective adenosine receptor antagonists". Journal of Medicinal Chemistry 45 (7): 1500–1510. March 2002. doi:10.1021/jm011049y. PMID 11906291.
- "The adenosine 2b receptor is recruited to the plasma membrane and associates with E3KARP and Ezrin upon agonist stimulation". The Journal of Biological Chemistry 277 (36): 33188–33195. September 2002. doi:10.1074/jbc.M202522200. PMID 12080047.
- "Mast cell-mediated stimulation of angiogenesis: cooperative interaction between A2B and A3 adenosine receptors". Circulation Research 92 (5): 485–492. March 2003. doi:10.1161/01.RES.0000061572.10929.2D. PMID 12600879.
- "Coordinated adenine nucleotide phosphohydrolysis and nucleoside signaling in posthypoxic endothelium: role of ectonucleotidases and adenosine A2B receptors". The Journal of Experimental Medicine 198 (5): 783–796. September 2003. doi:10.1084/jem.20030891. PMID 12939345.
- "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". Journal of Immunology 172 (12): 7726–7733. June 2004. doi:10.4049/jimmunol.172.12.7726. PMID 15187156.
- "Interferon-gamma down-regulates adenosine 2b receptor-mediated signaling and short circuit current in the intestinal epithelia by inhibiting the expression of adenylate cyclase". The Journal of Biological Chemistry 280 (6): 4048–4057. February 2005. doi:10.1074/jbc.M409577200. PMID 15550390.
External links
- "Adenosine Receptors: A2B". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2170.
- Human ADORA2B genome location and ADORA2B gene details page in the UCSC Genome Browser.
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