Genomes and Genes
Gene Symbol: Adora2a
Description: adenosine A2a receptor
Alias: A2AAR, A2aR, AA2AR, adenosine receptor A2a
- Huang S, Apasov S, Koshiba M, Sitkovsky M. Role of A2a extracellular adenosine receptor-mediated signaling in adenosine-mediated inhibition of T-cell activation and expansion. Blood. 1997;90:1600-10 pubmed..These studies suggest the possible role of adenosine receptors in the regulation of lymphocyte expansion and point to the downregulation of A2a purinergic receptors on T cells as a potentially attractive pharmacologic target. ..
- Raskovalova T, Huang X, Sitkovsky M, Zacharia L, Jackson E, Gorelik E. Gs protein-coupled adenosine receptor signaling and lytic function of activated NK cells. J Immunol. 2005;175:4383-91 pubmed..Adenosine is an endogenous ligand for four different adenosine receptor (AdoR) subtypes (AdoRA1, AdoRA2A, AdoRA2B, and AdoRA3)...
- Deaglio S, Dwyer K, Gao W, Friedman D, Usheva A, Erat A, et al. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J Exp Med. 2007;204:1257-65 pubmed..We conclude that CD39 and CD73 are surface markers of T reg cells that impart a specific biochemical signature characterized by adenosine generation that has functional relevance for cellular immunoregulation. ..
- Ohta A, Ohta A, Madasu M, Kini R, Subramanian M, Goel N, et al. A2A adenosine receptor may allow expansion of T cells lacking effector functions in extracellular adenosine-rich microenvironments. J Immunol. 2009;183:5487-93 pubmed publisherImmunosuppressive signaling via the A2A adenosine receptor (A2AR) provokes a mechanism that protects inflamed tissues from excessive damage by immune cells...
- Zhang L, Yang N, Wang S, Huang B, Li F, Tan H, et al. Adenosine 2A receptor is protective against renal injury in MRL/lpr mice. Lupus. 2011;20:667-77 pubmed publisher..Adenosine is considered as a potent endogenous anti-inflammatory and immunosuppressive molecule. We examined the roles of A2A-adenosine receptor (A(2A)R) in the progression of lupus nephritis...
- Huang Z, Qu W, Eguchi N, Chen J, Schwarzschild M, Fredholm B, et al. Adenosine A2A, but not A1, receptors mediate the arousal effect of caffeine. Nat Neurosci. 2005;8:858-9 pubmed..Thus, caffeine-induced wakefulness depends on adenosine A2A receptors. ..
- De Ponti C, Carini R, Alchera E, Nitti M, Locati M, Albano E, et al. Adenosine A2a receptor-mediated, normoxic induction of HIF-1 through PKC and PI-3K-dependent pathways in macrophages. J Leukoc Biol. 2007;82:392-402 pubmed
- Bastia E, Xu Y, Scibelli A, Day Y, Linden J, Chen J, et al. A crucial role for forebrain adenosine A(2A) receptors in amphetamine sensitization. Neuropsychopharmacology. 2005;30:891-900 pubmed..Thus activation of brain A(2A)Rs plays a critical role in developing augmented psychomotor responses to repeated psychostimulant exposure. ..
- Svenningsson P, Lindskog M, Ledent C, Parmentier M, Greengard P, Fredholm B, et al. Regulation of the phosphorylation of the dopamine- and cAMP-regulated phosphoprotein of 32 kDa in vivo by dopamine D1, dopamine D2, and adenosine A2A receptors. Proc Natl Acad Sci U S A. 2000;97:1856-60 pubmed..The results also underscore the fact that the adenosine system plays a role in the generation of responses to dopamine D(2) antagonists in vivo. ..
- Day Y, Li Y, Rieger J, Ramos S, Okusa M, Linden J. A2A adenosine receptors on bone marrow-derived cells protect liver from ischemia-reperfusion injury. J Immunol. 2005;174:5040-6 pubmed..The data suggest that activation of the A(2A)R on bone marrow-derived cells is primarily responsible for protecting the liver from reperfusion injury. ..
- Moriyama K, Sitkovsky M. Adenosine A2A receptor is involved in cell surface expression of A2B receptor. J Biol Chem. 2010;285:39271-88 pubmed publisherThe A2A and A2B adenosine receptors (A2AR and A2BR) are implicated in many physiological processes. However, the mechanisms of their intracellular maturation and trafficking are poorly understood...
- Chen J, Huang Z, Ma J, Zhu J, Moratalla R, Standaert D, et al. A(2A) adenosine receptor deficiency attenuates brain injury induced by transient focal ischemia in mice. J Neurosci. 1999;19:9192-200 pubmed
- Nishi A, Liu F, Matsuyama S, Hamada M, Higashi H, Nairn A, et al. Metabotropic mGlu5 receptors regulate adenosine A2A receptor signaling. Proc Natl Acad Sci U S A. 2003;100:1322-7 pubmed..The results demonstrate that mGlu5 receptors potentiate adenosine A(2A)DARPP-32 signaling by stimulating the adenosine A(2A) receptor-mediated formation of cAMP in an extracellular signal-regulated kinase-dependent manner. ..
- Naganuma M, Wiznerowicz E, Lappas C, Linden J, Worthington M, Ernst P. Cutting edge: Critical role for A2A adenosine receptors in the T cell-mediated regulation of colitis. J Immunol. 2006;177:2765-9 pubmed..These data suggest that A(2A)AR play a novel role in the control of T cell-mediated colitis by suppressing the expression of proinflammatory cytokines while sparing anti-inflammatory activity mediated by IL-10 and TGF-beta. ..
- Eckle T, Krahn T, Grenz A, Kohler D, Mittelbronn M, Ledent C, et al. Cardioprotection by ecto-5'-nucleotidase (CD73) and A2B adenosine receptors. Circulation. 2007;115:1581-90 pubmed
- Pinhal Enfield G, Ramanathan M, Hasko G, Vogel S, Salzman A, Boons G, et al. An angiogenic switch in macrophages involving synergy between Toll-like receptors 2, 4, 7, and 9 and adenosine A(2A) receptors. Am J Pathol. 2003;163:711-21 pubmed..This angiogenic switch may play an important role in ischemia when TLR agonists are present, providing an interface between innate immunity and wound healing. ..
- Quiroz C, Lujan R, Uchigashima M, Simões A, Lerner T, Borycz J, et al. Key modulatory role of presynaptic adenosine A2A receptors in cortical neurotransmission to the striatal direct pathway. ScientificWorldJournal. 2009;9:1321-44 pubmed publisher..Presynaptic striatal A2A receptors could provide a new target for the treatment of neuropsychiatric disorders. ..
- Katebi M, Fernandez P, Chan E, Cronstein B. Adenosine A2A receptor blockade or deletion diminishes fibrocyte accumulation in the skin in a murine model of scleroderma, bleomycin-induced fibrosis. Inflammation. 2008;31:299-303 pubmed publisher..Moreover, these results provide further evidence that adenosine A(2A) receptors may represent a new target for the treatment of such fibrosing diseases as scleroderma or nephrogenic fibrosing dermopathy. ..
- Montesinos M, Desai A, Chen J, Yee H, Schwarzschild M, Fink J, et al. Adenosine promotes wound healing and mediates angiogenesis in response to tissue injury via occupancy of A(2A) receptors. Am J Pathol. 2002;160:2009-18 pubmed..Thus, targeting the adenosine A(2A) receptor is a novel approach to promoting wound healing and angiogenesis in normal individuals and those suffering from chronic wounds. ..
- Zhong H, Shlykov S, Molina J, Sanborn B, Jacobson M, Tilley S, et al. Activation of murine lung mast cells by the adenosine A3 receptor. J Immunol. 2003;171:338-45 pubmed..These results demonstrate that the A(3) adenosine receptor plays an important role in adenosine-mediated murine lung mast cell degranulation. ..
- Ohta A, Gorelik E, Prasad S, Ronchese F, Lukashev D, Wong M, et al. A2A adenosine receptor protects tumors from antitumor T cells. Proc Natl Acad Sci U S A. 2006;103:13132-7 pubmedThe A2A adenosine receptor (A2AR) has been shown to be a critical and nonredundant negative regulator of immune cells in protecting normal tissues from inflammatory damage...
- Day Y, Marshall M, Huang L, McDuffie M, Okusa M, Linden J. Protection from ischemic liver injury by activation of A2A adenosine receptors during reperfusion: inhibition of chemokine induction. Am J Physiol Gastrointest Liver Physiol. 2004;286:G285-93 pubmed..We speculate that inhibition of chemokine and cytokine production limits inflammation and contributes to tissue protection by the A(2A)AR agonist ATL146e. ..
- Leibovich S, Chen J, Pinhal Enfield G, Belem P, Elson G, Rosania A, et al. Synergistic up-regulation of vascular endothelial growth factor expression in murine macrophages by adenosine A(2A) receptor agonists and endotoxin. Am J Pathol. 2002;160:2231-44 pubmed
- Day Y, Huang L, McDuffie M, Rosin D, Ye H, Chen J, et al. Renal protection from ischemia mediated by A2A adenosine receptors on bone marrow-derived cells. J Clin Invest. 2003;112:883-91 pubmed..chimeric mice in which BM was ablated by lethal radiation and reconstituted with donor BM cells derived from GFP, A2AR-KO, or WT mice to produce GFP-->WT, A2A-KO-->WT, or WT-->WT mouse chimera...
- Figler R, Wang G, Srinivasan S, Jung D, Zhang Z, Pankow J, et al. Links between insulin resistance, adenosine A2B receptors, and inflammatory markers in mice and humans. Diabetes. 2011;60:669-79 pubmed publisher..We hypothesize that increased A(2B)R signaling in diabetes increases insulin resistance in part by elevating proinflammatory mediators. Selective A(2B)R blockers may be useful to treat insulin resistance. ..
- Ohta A, Sitkovsky M. Role of G-protein-coupled adenosine receptors in downregulation of inflammation and protection from tissue damage. Nature. 2001;414:916-20 pubmed..We suggest that A2a adenosine receptors are a critical part of the physiological negative feedback mechanism for limitation and termination of both tissue-specific and systemic inflammatory responses. ..
- Nadeem A, Ponnoth D, Ansari H, Batchelor T, Dey R, Ledent C, et al. A2A adenosine receptor deficiency leads to impaired tracheal relaxation via NADPH oxidase pathway in allergic mice. J Pharmacol Exp Ther. 2009;330:99-108 pubmed publisher..In conclusion, this study shows that A(2A)AR deficiency causes increased NADPH oxidase activation leading to decreased tracheal relaxation via altered cAMP-PKA signaling and ROS generation. ..
- Hamad E, Li X, Song J, Zhang X, Myers V, Funakoshi H, et al. Effects of cardiac-restricted overexpression of the A(2A) adenosine receptor on adriamycin-induced cardiotoxicity. Am J Physiol Heart Circ Physiol. 2010;298:H1738-47 pubmed publisher..Our data have direct relevance on the clinical use of adenosine agonists or antagonists in the treatment of patients undergoing adriamycin therapy. ..
- Ponnoth D, Sanjani M, Ledent C, Roush K, Krahn T, Mustafa S. Absence of adenosine-mediated aortic relaxation in A(2A) adenosine receptor knockout mice. Am J Physiol Heart Circ Physiol. 2009;297:H1655-60 pubmed publisher..In conclusion, A(2A)AR KO mice had significantly lower aortic relaxation and endothelial function, suggesting that the A(2A)AR plays an important role in vasorelaxation, probably through an endothelium-dependent mechanism. ..
- Reutershan J, Cagnina R, Chang D, Linden J, Ley K. Therapeutic anti-inflammatory effects of myeloid cell adenosine receptor A2a stimulation in lipopolysaccharide-induced lung injury. J Immunol. 2007;179:1254-63 pubmedTo determine the role of the adenosine receptor A2a in a murine model of LPS-induced lung injury, migration of polymorphonuclear leukocytes (PMNs) into the different compartments of the lung was determined by flow cytometry, microvascular ..
- Koeppen M, Eckle T, Eltzschig H. Selective deletion of the A1 adenosine receptor abolishes heart-rate slowing effects of intravascular adenosine in vivo. PLoS ONE. 2009;4:e6784 pubmed publisher..While adenosine can signal through any of four ARs (A1AR, A2AAR, A2BAR, A3AR), previous ex vivo studies implicated the A1AR in the heart-rate slowing effects...
- Murphree L, Sullivan G, Marshall M, Linden J. Lipopolysaccharide rapidly modifies adenosine receptor transcripts in murine and human macrophages: role of NF-kappaB in A(2A) adenosine receptor induction. Biochem J. 2005;391:575-80 pubmed
- Ribé D, Sawbridge D, Thakur S, Hussey M, Ledent C, Kitchen I, et al. Adenosine A2A receptor signaling regulation of cardiac NADPH oxidase activity. Free Radic Biol Med. 2008;44:1433-42 pubmed publisher..The adenosine A2A receptor (A2AR) has been found to be expressed in cardiac myocytes and coronary endothelial cells...
- Ledent C, Vaugeois J, Schiffmann S, Pedrazzini T, El Yacoubi M, Vanderhaeghen J, et al. Aggressiveness, hypoalgesia and high blood pressure in mice lacking the adenosine A2a receptor. Nature. 1997;388:674-8 pubmed..The A2a receptor (A2aR) is abundant in basal ganglia, vasculature and platelets, and stimulates adenylyl cyclase...
- Day Y, Huang L, Ye H, Linden J, Okusa M. Renal ischemia-reperfusion injury and adenosine 2A receptor-mediated tissue protection: role of macrophages. Am J Physiol Renal Physiol. 2005;288:F722-31 pubmed..We conclude that the full extent of IRI requires macrophages and that A(2A) agonist-mediated tissue protection is independent of activation of macrophage A(2A)Rs. ..
- Fredduzzi S, Moratalla R, Monopoli A, Cuellar B, Xu K, Ongini E, et al. Persistent behavioral sensitization to chronic L-DOPA requires A2A adenosine receptors. J Neurosci. 2002;22:1054-62 pubmed..Furthermore, they raise the possibility that the maladaptive dyskinetic responses to chronic l-DOPA treatment in Parkinson's disease may be attenuated by A(2A) receptor inactivation. ..
- Schwindinger W, Mihalcik L, Giger K, Betz K, Stauffer A, Linden J, et al. Adenosine A2A receptor signaling and golf assembly show a specific requirement for the gamma7 subtype in the striatum. J Biol Chem. 2010;285:29787-96 pubmed publisher..Collectively, these results further support the A(2A)R G-protein ?(olf)?(2)?(7) interface as a possible therapeutic target for Parkinson disease. ..
- Erdmann A, Gao Z, Jung U, Foley J, Borenstein T, Jacobson K, et al. Activation of Th1 and Tc1 cell adenosine A2A receptors directly inhibits IL-2 secretion in vitro and IL-2-driven expansion in vivo. Blood. 2005;105:4707-14 pubmed..Modulation of adenosine receptors may thus represent a suitable target primarily for inflammatory conditions mediated by Th1 and Tc1 cells. ..
- Brown R, Duncan J, Stagnitti M, Ledent C, Lawrence A. mGlu5 and adenosine A2A receptor interactions regulate the conditioned effects of cocaine. Int J Neuropsychopharmacol. 2012;15:995-1001 pubmed publisher..This functional interaction is supported by modulation of 4-(2-[7-amino-2-[2-furyl][1,2,4]triazolol[2,3-a][1,3,5]triazin-5-yl-amino]ethyl)phenol ([125I]ZM241385) binding to the A2A receptor by MTEP. ..
- Csóka B, Selmeczy Z, Koscsó B, Németh Z, Pacher P, Murray P, et al. Adenosine promotes alternative macrophage activation via A2A and A2B receptors. FASEB J. 2012;26:376-86 pubmed publisher..We propose that adenosine receptor activation suppresses inflammation and promotes tissue restitution, in part, by promoting alternative macrophage activation. ..
- Orr A, Orr A, Li X, Gross R, Traynelis S. Adenosine A(2A) receptor mediates microglial process retraction. Nat Neurosci. 2009;12:872-8 pubmed publisher..Our results indicate that purine nucleotides provide an opportunity for context-dependent shifts in receptor signaling. Thus, we reveal an unexpected chemotactic switch that generates a hallmark feature of CNS inflammation. ..
- Tebano M, Martire A, Potenza R, Grò C, Pepponi R, Armida M, et al. Adenosine A(2A) receptors are required for normal BDNF levels and BDNF-induced potentiation of synaptic transmission in the mouse hippocampus. J Neurochem. 2008;104:279-86 pubmed..These results indicate that the tonic activation of A(2A)Rs is required for BDNF-induced potentiation of synaptic transmission and for sustaining a normal BDNF tone in the hippocampus. ..
- Fredholm B. Adenosine, an endogenous distress signal, modulates tissue damage and repair. Cell Death Differ. 2007;14:1315-23 pubmed..This review will briefly summarize what is known and what is not in this regard. It is argued that drugs targeting adenosine receptors might be useful adjuncts in many therapeutic approaches. ..
- Lappas C, Rieger J, Linden J. A2A adenosine receptor induction inhibits IFN-gamma production in murine CD4+ T cells. J Immunol. 2005;174:1073-80 pubmed..We conclude that the rapid induction of the A(2A)AR mRNA in T cells provides a mechanism for limiting T cell activation and secondary macrophage activation in inflamed tissues. ..
- Yang J, Chen J, Fredholm B. Physiological roles of A1 and A2A adenosine receptors in regulating heart rate, body temperature, and locomotion as revealed using knockout mice and caffeine. Am J Physiol Heart Circ Physiol. 2009;296:H1141-9 pubmed publisher..The A(2A)R plays an important role in the modulation of O(2)C and LA by acute and chronic caffeine administration. There is also evidence for effects of higher doses of caffeine being independent of both A(1)R and A(2A)R. ..
- Yang J, Björklund O, Lindström Törnqvist K, Lindgren E, Eriksson T, Kahlström J, et al. Mice heterozygous for both A1 and A(2A) adenosine receptor genes show similarities to mice given long-term caffeine. J Appl Physiol (1985). 2009;106:631-9 pubmed publisher..Thus at least some aspects of long-term caffeine use can be mimicked by genetic manipulation of the A(1)R and A(2A)R. ..
- Li W, Dai S, An J, Xiong R, Li P, Chen X, et al. Genetic inactivation of adenosine A2A receptors attenuates acute traumatic brain injury in the mouse cortical impact model. Exp Neurol. 2009;215:69-76 pubmed publisher..These results suggest that the genetic inactivation of A(2A)R protects against TBI, which is mainly associated with the suppression of glutamate level. ..
- Shen H, Coelho J, Ohtsuka N, Canas P, Day Y, Huang Q, et al. A critical role of the adenosine A2A receptor in extrastriatal neurons in modulating psychomotor activity as revealed by opposite phenotypes of striatum and forebrain A2A receptor knock-outs. J Neurosci. 2008;28:2970-5 pubmed publisher..These results indicate that A(2A)Rs in striatal and extrastriatal neurons exert an opposing modulation of psychostimulant effects and provide the first direct demonstration of a predominant facilitatory role of extrastriatal A(2A)Rs. ..
- Wei C, Singer P, Coelho J, Boison D, Feldon J, Yee B, et al. Selective inactivation of adenosine A(2A) receptors in striatal neurons enhances working memory and reversal learning. Learn Mem. 2011;18:459-74 pubmed publisher..This study provides the first direct demonstration that targeting striatal A(2A)Rs may be an effective, novel strategy to facilitate cognitive flexibility under normal and pathologic conditions. ..
- Montesinos M, Shaw J, Yee H, Shamamian P, Cronstein B. Adenosine A(2A) receptor activation promotes wound neovascularization by stimulating angiogenesis and vasculogenesis. Am J Pathol. 2004;164:1887-92 pubmed