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Adenosine A2B receptor

{{cs1 config|name-list-style=vanc}}

{{Short description|Cell surface receptor found in humans}}

{{DISPLAYTITLE:Adenosine A2B receptor}}

{{Infobox_gene}}

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.{{cite web | title = Entrez Gene: ADORA2B adenosine A2b receptor| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=136}}

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.

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,{{cite journal | vauthors = Volpini R, Costanzi S, Lambertucci C, Taffi S, Vittori S, Klotz KN, Cristalli G | title = 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 = Journal of Medicinal Chemistry | volume = 45 | issue = 15 | pages = 3271–3279 | date = July 2002 | pmid = 12109910 | doi = 10.1021/jm0109762 }}{{cite journal | vauthors = Volpini R, Costanzi S, Lambertucci C, Vittori S, Cristalli G | title = Purine nucleosides bearing 1-alkynyl chains as adenosine receptor agonists | journal = Current Pharmaceutical Design | volume = 8 | issue = 26 | pages = 2285–2298 | year = 2002 | pmid = 12369946 | doi = 10.2174/1381612023392856 | url = http://www.bentham-direct.org/pages/content.php?CPD/2002/00000008/00000026/0002B.SGM | url-status = usurped | archive-url = https://archive.today/20130414131152/http://www.bentham-direct.org/pages/content.php?CPD/2002/00000008/00000026/0002B.SGM | archive-date = 2013-04-14 | url-access = subscription }}{{cite journal | vauthors = Baraldi PG, Tabrizi MA, Preti D, Bovero A, Romagnoli R, Fruttarolo F, Zaid NA, Moorman AR, Varani K, Gessi S, Merighi S, Borea PA | display-authors = 6 | title = Design, synthesis, and biological evaluation of new 8-heterocyclic xanthine derivatives as highly potent and selective human A2B adenosine receptor antagonists | journal = Journal of Medicinal Chemistry | volume = 47 | issue = 6 | pages = 1434–1447 | date = March 2004 | pmid = 14998332 | doi = 10.1021/jm0309654 }}{{cite journal | vauthors = Cacciari B, Pastorin G, Bolcato C, Spalluto G, Bacilieri M, Moro S | title = A2B adenosine receptor antagonists: recent developments | journal = Mini Reviews in Medicinal Chemistry | volume = 5 | issue = 12 | pages = 1053–1060 | date = December 2005 | pmid = 16375751 | doi = 10.2174/138955705774933374 | url = http://www.bentham-direct.org/pages/content.php?MRMC/2005/00000005/00000012/0001N.SGM | url-status = usurped | archive-url = https://archive.today/20130414141112/http://www.bentham-direct.org/pages/content.php?MRMC/2005/00000005/00000012/0001N.SGM | archive-date = 2013-04-14 | url-access = subscription }}{{cite journal | vauthors = Baraldi PG, Romagnoli R, Preti D, Fruttarolo F, Carrion MD, Tabrizi MA | title = Ligands for A2B adenosine receptor subtype | journal = Current Medicinal Chemistry | volume = 13 | issue = 28 | pages = 3467–3482 | year = 2006 | pmid = 17168717 | doi = 10.2174/092986706779010306 | url = http://www.bentham-direct.org/pages/content.php?CMC/2006/00000013/00000028/0008C.SGM | url-status = usurped | archive-url = https://archive.today/20130414075418/http://www.bentham-direct.org/pages/content.php?CMC/2006/00000013/00000028/0008C.SGM | archive-date = 2013-04-14 | url-access = subscription }}{{cite journal | vauthors = Beukers MW, Meurs I, Ijzerman AP | title = Structure-affinity relationships of adenosine A2B receptor ligands | journal = Medicinal Research Reviews | volume = 26 | issue = 5 | pages = 667–698 | date = September 2006 | pmid = 16847822 | doi = 10.1002/med.20069 | s2cid = 24390495 }}{{cite journal | vauthors = Elzein E, Kalla R, Li X, Perry T, Parkhill E, Palle V, Varkhedkar V, Gimbel A, Zeng D, Lustig D, Leung K, Zablocki J | display-authors = 6 | title = Novel 1,3-dipropyl-8-(1-heteroarylmethyl-1H-pyrazol-4-yl)-xanthine derivatives as high affinity and selective A2B adenosine receptor antagonists | journal = Bioorganic & Medicinal Chemistry Letters | volume = 16 | issue = 2 | pages = 302–306 | date = January 2006 | pmid = 16275090 | doi = 10.1016/j.bmcl.2005.10.002 }}{{cite journal | vauthors = 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 | display-authors = 6 | title = Design, synthesis, and structure-activity relationships of 1-,3-,8-, and 9-substituted-9-deazaxanthines at the human A2B adenosine receptor | journal = Journal of Medicinal Chemistry | volume = 49 | issue = 1 | pages = 282–299 | date = January 2006 | pmid = 16392813 | doi = 10.1021/jm0506221 }}{{cite journal | vauthors = Tabrizi MA, Baraldi PG, Preti D, Romagnoli R, Saponaro G, Baraldi S, Moorman AR, Zaid AN, Varani K, Borea PA | display-authors = 6 | title = 1,3-Dipropyl-8-(1-phenylacetamide-1H-pyrazol-3-yl)-xanthine derivatives as highly potent and selective human A(2B) adenosine receptor antagonists | journal = Bioorganic & Medicinal Chemistry | volume = 16 | issue = 5 | pages = 2419–2430 | date = March 2008 | pmid = 18077171 | doi = 10.1016/j.bmc.2007.11.058 }}{{cite journal | vauthors = 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 | display-authors = 6 | title = 1-, 3- and 8-substituted-9-deazaxanthines as potent and selective antagonists at the human A2B adenosine receptor | journal = Bioorganic & Medicinal Chemistry | volume = 16 | issue = 6 | pages = 2852–2869 | date = March 2008 | pmid = 18226909 | doi = 10.1016/j.bmc.2008.01.002 }} and research into their potential therapeutic applications is ongoing.{{cite journal | vauthors = Volpini R, Costanzi S, Vittori S, Cristalli G, Klotz KN | title = Medicinal chemistry and pharmacology of A2B adenosine receptors | journal = Current Topics in Medicinal Chemistry | volume = 3 | issue = 4 | pages = 427–443 | year = 2003 | pmid = 12570760 | doi = 10.2174/1568026033392264 | url = http://www.bentham-direct.org/pages/content.php?CTMC/2003/00000003/00000004/0007R.SGM | url-status = usurped | archive-url = https://archive.today/20130414065741/http://www.bentham-direct.org/pages/content.php?CTMC/2003/00000003/00000004/0007R.SGM | archive-date = 2013-04-14 | url-access = subscription }}{{cite journal | vauthors = Gao ZG, Jacobson KA | title = Emerging adenosine receptor agonists | journal = Expert Opinion on Emerging Drugs | volume = 12 | issue = 3 | pages = 479–492 | date = September 2007 | pmid = 17874974 | doi = 10.1517/14728214.12.3.479 | s2cid = 13777846 | url = https://zenodo.org/record/1236313 | pmc = 11790296 }}{{cite journal | vauthors = 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 | display-authors = 6 | title = Blockade of adenosine A2B receptors ameliorates murine colitis | journal = British Journal of Pharmacology | volume = 155 | issue = 1 | pages = 127–137 | date = September 2008 | pmid = 18536750 | pmc = 2440087 | doi = 10.1038/bjp.2008.227 }}{{cite journal | vauthors = Haskó G, Linden J, Cronstein B, Pacher P | title = Adenosine receptors: therapeutic aspects for inflammatory and immune diseases | journal = Nature Reviews. Drug Discovery | volume = 7 | issue = 9 | pages = 759–770 | date = September 2008 | pmid = 18758473 | pmc = 2568887 | doi = 10.1038/nrd2638 }}{{cite journal | vauthors = Ham J, Rees DA | title = The adenosine a2b receptor: its role in inflammation | journal = Endocrine, Metabolic & Immune Disorders Drug Targets | volume = 8 | issue = 4 | pages = 244–254 | date = December 2008 | pmid = 19075778 | doi = 10.2174/187153008786848303 | url = http://www.bentham-direct.org/pages/content.php?EMIDDT/2008/00000008/00000004/0003V.SGM | url-status = usurped | archive-url = https://archive.today/20130414105722/http://www.bentham-direct.org/pages/content.php?EMIDDT/2008/00000008/00000004/0003V.SGM | archive-date = 2013-04-14 | url-access = subscription }}{{cite journal | vauthors = Kim MO, Kim MH, Lee SH, Suh HN, Lee YJ, Lee MY, Han HJ | title = 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 = Journal of Cellular Physiology | volume = 219 | issue = 3 | pages = 752–759 | date = June 2009 | pmid = 19194991 | doi = 10.1002/jcp.21721 | s2cid = 11066973 | doi-access = free }}{{cite journal | vauthors = Tay AH, Prieto-Díaz R, Neo S, Tong L, Chen X, Carannante V, Önfelt B, Hartman J, Haglund F, Majellaro M, Azuaje J, Garcia-Mera X, Brea JM, Loza MI, Jespers W, Gutierrez-de-Teran H, Sotelo E, Lundqvist A | display-authors = 6 | title = A2B adenosine receptor antagonists rescue lymphocyte activity in adenosine-producing patient-derived cancer models | journal = Journal for Immunotherapy of Cancer | volume = 10 | issue = 5 | pages = e004592 | date = May 2022 | pmid = 35580926 | pmc = 9115112 | doi = 10.1136/jitc-2022-004592 }}

=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:{{cite journal | vauthors = Stefanachi A, Nicolotti O, Leonetti F, Cellamare S, Campagna F, Loza MI, Brea JM, Mazza F, Gavuzzo E, Carotti A | display-authors = 6 | title = 1,3-Dialkyl-8-(hetero)aryl-9-OH-9-deazaxanthines as potent A2B adenosine receptor antagonists: design, synthesis, structure-affinity and structure-selectivity relationships | journal = Bioorganic & Medicinal Chemistry | volume = 16 | issue = 22 | pages = 9780–9789 | date = November 2008 | pmid = 18938084 | doi = 10.1016/j.bmc.2008.09.067 }} antagonist, high affinity and good subtype selectivity
  • ISAM-R56A: non-xanthinic high affinity selective antagonist (Ki: 1.50 nM)
  • ISAM-140:{{cite journal | vauthors = El Maatougui A, Azuaje J, González-Gómez M, Miguez G, Crespo A, Carbajales C, Escalante L, García-Mera X, Gutiérrez-de-Terán H, Sotelo E | display-authors = 6 | title = Discovery of Potent and Highly Selective A2B Adenosine Receptor Antagonist Chemotypes | journal = Journal of Medicinal Chemistry | volume = 59 | issue = 5 | pages = 1967–1983 | date = March 2016 | pmid = 26824742 | doi = 10.1021/acs.jmedchem.5b01586 }} non-xanthinic selective antagonist (Ki = 3.49 nM).
  • ISAM-R324A:{{cite journal | vauthors = Prieto-Díaz R, González-Gómez M, Fojo-Carballo H, Azuaje J, El Maatougui A, Majellaro M, Loza MI, Brea J, Fernández-Dueñas V, Paleo MR, Díaz-Holguín A, Garcia-Pinel B, Mallo-Abreu A, Estévez JC, Andújar-Arias A, García-Mera X, Gomez-Tourino I, Ciruela F, Salas CO, Gutiérrez-de-Terán H, Sotelo E | display-authors = 6 | title = Exploring the Effect of Halogenation in a Series of Potent and Selective A2B Adenosine Receptor Antagonists | journal = Journal of Medicinal Chemistry | pages = 890–912 | date = December 2022 | volume = 66 | issue = 1 | pmid = 36517209 | doi = 10.1021/acs.jmedchem.2c01768 | pmc = 9841532 }} Soluble and metabolically stable non-xanthinic selective antagonist (Ki = 6.10 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:{{cite journal | vauthors = Jiang J, Seel CJ, Temirak A, Namasivayam V, Arridu A, Schabikowski J, Baqi Y, Hinz S, Hockemeyer J, Müller CE | display-authors = 6 | title = A2B Adenosine Receptor Antagonists with Picomolar Potency | journal = Journal of Medicinal Chemistry | volume = 62 | issue = 8 | pages = 4032–4055 | date = April 2019 | pmid = 30835463 | doi = 10.1021/acs.jmedchem.9b00071 | s2cid = 73472174 }} xanthinic antagonist with picomolar potency

References

{{reflist|30em}}

Further reading

{{refbegin|30em}}

  • {{cite journal | vauthors = Stiles GL | title = Adenosine receptors | journal = The Journal of Biological Chemistry | volume = 267 | issue = 10 | pages = 6451–6454 | date = April 1992 | pmid = 1551861 | doi = 10.1016/S0021-9258(19)50445-8 | doi-access = free }}
  • {{cite journal | vauthors = Pierce KD, Furlong TJ, Selbie LA, Shine J | title = Molecular cloning and expression of an adenosine A2b receptor from human brain | journal = Biochemical and Biophysical Research Communications | volume = 187 | issue = 1 | pages = 86–93 | date = August 1992 | pmid = 1325798 | doi = 10.1016/S0006-291X(05)81462-7 }}
  • {{cite journal | vauthors = Li Q, Han X, Lan X, Hong X, Li Q, Gao Y, Luo T, Yang Q, Koehler RC, Zhai Y, Zhou J, Wang J | display-authors = 6 | title = Inhibition of tPA-induced hemorrhagic transformation involves adenosine A2b receptor activation after cerebral ischemia | journal = Neurobiology of Disease | volume = 108 | pages = 173–182 | date = December 2017 | pmid = 28830843 | pmc = 5675803 | doi = 10.1016/j.nbd.2017.08.011 }}
  • {{cite journal | vauthors = Jacobson MA, Johnson RG, Luneau CJ, Salvatore CA | title = Cloning and chromosomal localization of the human A2b adenosine receptor gene (ADORA2B) and its pseudogene | journal = Genomics | volume = 27 | issue = 2 | pages = 374–376 | date = May 1995 | pmid = 7558011 | doi = 10.1006/geno.1995.1061 }}
  • {{cite journal | vauthors = Townsend-Nicholson A, Baker E, Sutherland GR, Schofield PR | title = Localization of the adenosine A2b receptor subtype gene (ADORA2B) to chromosome 17p11.2-p12 by FISH and PCR screening of somatic cell hybrids | journal = Genomics | volume = 25 | issue = 2 | pages = 605–607 | date = January 1995 | pmid = 7790006 | doi = 10.1016/0888-7543(95)80074-V | authorlink3 = Grant Robert Sutherland }}
  • {{cite journal | vauthors = Strohmeier GR, Reppert SM, Lencer WI, Madara JL | title = The A2b adenosine receptor mediates cAMP responses to adenosine receptor agonists in human intestinal epithelia | journal = The Journal of Biological Chemistry | volume = 270 | issue = 5 | pages = 2387–2394 | date = February 1995 | pmid = 7836474 | doi = 10.1074/jbc.270.5.2387 | doi-access = free }}
  • {{cite journal | vauthors = Feoktistov I, Murray JJ, Biaggioni I | title = Positive modulation of intracellular Ca2+ levels by adenosine A2b receptors, prostacyclin, and prostaglandin E1 via a cholera toxin-sensitive mechanism in human erythroleukemia cells | journal = Molecular Pharmacology | volume = 45 | issue = 6 | pages = 1160–1167 | date = June 1994 | pmid = 8022409 }}
  • {{cite journal | vauthors = Mirabet M, Herrera C, Cordero OJ, Mallol J, Lluis C, Franco R | title = Expression of A2B adenosine receptors in human lymphocytes: their role in T cell activation | journal = Journal of Cell Science | volume = 112 ( Pt 4) | issue = 4 | pages = 491–502 | date = February 1999 | pmid = 9914161 | doi = 10.1242/jcs.112.4.491 }}
  • {{cite journal | vauthors = Feoktistov I, Goldstein AE, Biaggioni I | title = 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 | journal = Molecular Pharmacology | volume = 55 | issue = 4 | pages = 726–734 | date = April 1999 | pmid = 10101031 }}
  • {{cite journal | vauthors = Corset V, Nguyen-Ba-Charvet KT, Forcet C, Moyse E, Chédotal A, Mehlen P | title = Netrin-1-mediated axon outgrowth and cAMP production requires interaction with adenosine A2b receptor | journal = Nature | volume = 407 | issue = 6805 | pages = 747–750 | date = October 2000 | pmid = 11048721 | doi = 10.1038/35037600 | s2cid = 4423128 | bibcode = 2000Natur.407..747C }}
  • {{cite journal | vauthors = Herrera C, Casadó V, Ciruela F, Schofield P, Mallol J, Lluis C, Franco R | title = Adenosine A2B receptors behave as an alternative anchoring protein for cell surface adenosine deaminase in lymphocytes and cultured cells | journal = Molecular Pharmacology | volume = 59 | issue = 1 | pages = 127–134 | date = January 2001 | pmid = 11125033 | doi = 10.1124/mol.59.1.127 }}
  • {{cite journal | vauthors = Christofi FL, Zhang H, Yu JG, Guzman J, Xue J, Kim M, Wang YZ, Cooke HJ | display-authors = 6 | title = Differential gene expression of adenosine A1, A2a, A2b, and A3 receptors in the human enteric nervous system | journal = The Journal of Comparative Neurology | volume = 439 | issue = 1 | pages = 46–64 | date = October 2001 | pmid = 11579381 | doi = 10.1002/cne.1334 | s2cid = 46222306 }}
  • {{cite journal | vauthors = Hayallah AM, Sandoval-Ramírez J, Reith U, Schobert U, Preiss B, Schumacher B, Daly JW, Müller CE | display-authors = 6 | title = 1,8-disubstituted xanthine derivatives: synthesis of potent A2B-selective adenosine receptor antagonists | journal = Journal of Medicinal Chemistry | volume = 45 | issue = 7 | pages = 1500–1510 | date = March 2002 | pmid = 11906291 | doi = 10.1021/jm011049y }}
  • {{cite journal | vauthors = Sitaraman SV, Wang L, Wong M, Bruewer M, Hobert M, Yun CH, Merlin D, Madara JL | display-authors = 6 | title = The adenosine 2b receptor is recruited to the plasma membrane and associates with E3KARP and Ezrin upon agonist stimulation | journal = The Journal of Biological Chemistry | volume = 277 | issue = 36 | pages = 33188–33195 | date = September 2002 | pmid = 12080047 | doi = 10.1074/jbc.M202522200 | doi-access = free }}
  • {{cite journal | vauthors = Feoktistov I, Ryzhov S, Goldstein AE, Biaggioni I | title = Mast cell-mediated stimulation of angiogenesis: cooperative interaction between A2B and A3 adenosine receptors | journal = Circulation Research | volume = 92 | issue = 5 | pages = 485–492 | date = March 2003 | pmid = 12600879 | doi = 10.1161/01.RES.0000061572.10929.2D | s2cid = 10346424 | doi-access = }}
  • {{cite journal | vauthors = Eltzschig HK, Ibla JC, Furuta GT, Leonard MO, Jacobson KA, Enjyoji K, Robson SC, Colgan SP | display-authors = 6 | title = Coordinated adenine nucleotide phosphohydrolysis and nucleoside signaling in posthypoxic endothelium: role of ectonucleotidases and adenosine A2B receptors | journal = The Journal of Experimental Medicine | volume = 198 | issue = 5 | pages = 783–796 | date = September 2003 | pmid = 12939345 | pmc = 2194189 | doi = 10.1084/jem.20030891 }}
  • {{cite journal | vauthors = Ryzhov S, Goldstein AE, Matafonov A, Zeng D, Biaggioni I, Feoktistov I | title = 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 = Journal of Immunology | volume = 172 | issue = 12 | pages = 7726–7733 | date = June 2004 | pmid = 15187156 | doi = 10.4049/jimmunol.172.12.7726 | doi-access = free }}
  • {{cite journal | vauthors = Kolachala V, Asamoah V, Wang L, Srinivasan S, Merlin D, Sitaraman SV | title = Interferon-gamma down-regulates adenosine 2b receptor-mediated signaling and short circuit current in the intestinal epithelia by inhibiting the expression of adenylate cyclase | journal = The Journal of Biological Chemistry | volume = 280 | issue = 6 | pages = 4048–4057 | date = February 2005 | pmid = 15550390 | doi = 10.1074/jbc.M409577200 | doi-access = free }}

{{refend}}

External links

  • {{cite web | url = http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2170 | title = Adenosine Receptors: A2B | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology | access-date = 2008-11-25 | archive-date = 2016-03-03 | archive-url = https://web.archive.org/web/20160303165806/http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2170 | url-status = dead }}
  • {{UCSC gene info|ADORA2B}}

{{G protein-coupled receptors}}

{{Adenosinergics}}

Category:Adenosine receptors