Adenosine receptor targeting in health and disease

Expert Opinion on Investigational Drugs

Volumn 20, Issue 12, 2011, Pages 1591-1609

  Gessi, Stefania ^a   Merighi, Stefania ^a   Fazzi, Debora ^a   Stefanelli, Angela ^a   Varani, Katia ^a   Borea, Pier Andrea ^b  

^a UNIVERSITY OF FERRARA   (Italy)

^b UNIVERSITY OF FERRARA   (Italy)

Author keywords

Adenosine receptors; Cancer; Cardiovascular diseases; Health; Inflammation; Neurological diseases; Respiratory disorders

Indexed keywords

6 N (3 IODOBENZYL)ADENOSINE 5' N METHYLCARBOXAMIDE; ADENOSINE A1 RECEPTOR; ADENOSINE A1 RECEPTOR AGONIST; ADENOSINE A2A RECEPTOR; ADENOSINE A2B RECEPTOR; ADENOSINE A3 RECEPTOR; ADENOSINE RECEPTOR; ADENOSINE RECEPTOR BLOCKING AGENT; ADENOSINE RECEPTOR STIMULATING AGENT; CAPADENOSON; CF 102; CVT 3619; CVT 6883; DERENOFYLLINE; DOXOFYLLINE; GS 6201; METHOTREXATE; PJ 875; ROLOFYLLINE; SELODENOSON; T 62; TECADENOSON; THEOPHYLLINE; TONAPOFYLLINE; UNCLASSIFIED DRUG;

ARTHRITIS; ASTHMA; CARDIOVASCULAR SYSTEM; CENTRAL NERVOUS SYSTEM; CHRONIC OBSTRUCTIVE LUNG DISEASE; CONGESTIVE HEART FAILURE; DIABETES MELLITUS; DIARRHEA; DRUG DESIGN; DRUG DEVELOPMENT; DRUG TARGETING; DRY EYE; GLAUCOMA; HEART ARRHYTHMIA; HEART ATRIUM FIBRILLATION; HEART FAILURE; HEPATITIS C; HUMAN; INFLAMMATION; KIDNEY FAILURE; LIPOPROTEIN DISORDER; LIVER CELL CARCINOMA; LIVER DISEASE; METABOLIC DISORDER; NEOPLASM; NEUROPATHIC PAIN; NONHUMAN; OSTEOARTHRITIS; PROTEIN FUNCTION; PROTEIN TARGETING; PSORIASIS; RESPIRATORY SYSTEM; REVIEW; RHEUMATOID ARTHRITIS; UVEITIS;

ADENOSINE; DISEASE; DRUG DISCOVERY; HEALTH; HUMANS; MOLECULAR TARGETED THERAPY; RECEPTORS, PURINERGIC P1; SIGNAL TRANSDUCTION;

EID: 81555196344     PISSN: 13543784     EISSN: 17447658     Source Type: Journal    
DOI: 10.1517/13543784.2011.627853     Document Type: Review

References (178)

1. Colgan SP, Eltzschig HK, Eckle T, et al. Physiological roles for ecto-5′-nucleotidase (CD73). Purinergic Signal 2006;20:351-60
2. Fredholm BB, IJzerman AP, Jacobson KA, et al. International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacol Rev 2001;53:527-52 (Pubitemid 33136237)
3. Fredholm BB. Adenosine receptors as drug targets. Exp Cell Res 2010;316:1284-8
4. Hasko G, Cronstein BN. Adenosine: an endogenous regulator of innate immunity. Trends Immunol 2004;25:33-9 (Pubitemid 38032805)
5. Linden J. Adenosine in tissue protection and tissue regeneration. Mol Pharmacol 2005;67:1385-7 (Pubitemid 40594134)
6. Hasko G, Linden J, Cronstein B, et al. Adenosine receptors: therapeutic aspects for inflammatory and immune diseases. Nat Rev Drug Discov 2008;7:759-70
7. Ralevic V, Burnstock G. Receptors for purines and pyrimidines. Pharmacol Rev 1998;50:413-92 (Pubitemid 28477681)
8. Van Calker DM, Muller M, Hamprecht B. Adenosine regulates via two different types of receptors, the accumulation of cyclic AMP in cultured brain cells. J Neurochem 1979;33:999-1005 (Pubitemid 10188731)
9. Jajoo S, Mukherjea D, Kumar S, et al. Role of beta-arrestin1/ERK MAP kinase pathway in regulating adenosine A1 receptor desensitization and recovery. Am J Physiol Cell Physiol 2010;298:C56-65
10. Eltzschig HK, Rivera-Nieves J, Colgan SP. Targeting the A2B adenosine receptor during gastrointestinal ischemia and inflammation. Expert Opin Ther Targets 2009;13:1267-77
11. Boison D. Adenosine as a neuromodulator in neurological diseases. Curr Opin Pharmacol 2007;8:1-6
12. Gong QJ, Li YY, Xin WJ, et al. Differential effects of adenosine A1 receptor on pain-related behavior in normal and nerve-injured rats. Brain Res 2010;1361:23-30
13. Nascimento FP, Figueredo SM, Marcon R, et al. Inosine reduces pain-related behavior in mice: involvement of adenosine A1 and A2A receptor subtypes and protein kinase C pathways. J Pharmacol Exp Ther 2010;334:590-8
14. Sowa NA, Street SE, Vihko P, et al. Prostatic acid phosphatase reduces thermal sensitivity and chronic pain sensitization by depleting phosphatidylinositol 4,5-bisphosphate. J Neurosci 2010;30:10282-93
15. Gan TJ, Habib AS. Adenosine as a non-opioid analgesic in the perioperative setting. Anaesth Analg 2007;105:487-94 (Pubitemid 47196432)
16. Schmidt AP, Bohmer AE, Antunes C, et al. Anti-nociceptive properties of the xanthine oxidase inhibitor allopurinol in mice: role of A1 adenosine receptors. Br J Pharmacol 2009;156:163-72
17. Romagnoli R, Baraldi PG, Tabrizi MA, et al. Allosteric enhancers of A1 adenosine receptors: state of the art and new horizons for drug development. Curr Med Chem 2010;17:3488-502
18. Baraldi PG, Zaid AN, Lampronti I, et al. Synthesis and biological effects of a new series of 2-amino-3-benzoylthiophenes as allosteric enhancers of A1-adenosine receptor. Bioorg Med Chem Lett 2000;10:1953-7 (Pubitemid 30663348)
19. Baraldi PG, Romagnoli R, Pavani MG, et al. Synthesis and biological effects of novel 2-amino-3-naphthoylthiophenes as allosteric enhancers of the A1 adenosine receptor. J Med Chem 2003;46:794-809 (Pubitemid 36258870)
20. Russo C, Arcidiacono G, Polosa R. Adenosine receptors: promising targets for the development of novel therapeutics and diagnostics for asthma. Fundam Clin Pharmacol 2006;20:9-19
21. Baraldi PG, Tabrizi MA, Gessi S, et al. Adenosine receptor antagonists: translating medicinal chemistry and pharmacology into clinical utility. Chem Rev 2008;108:238-63 (Pubitemid 351176408)
22. Driver AG, Kukoly CA, Ali S, et al. Adenosine in bronchoalveolar lavage fluid in asthma. Am Rev Respir Dis 1993;148:91-7 (Pubitemid 23187224)
23. Brown RA, Clarke GW, Ledbetter CL, et al. Elevated expression of adenosine A1 receptor in bronchial biopsies from asthmatic subjects. Eur Respir J 2008;31:1-9
24. Ponnoth DS, Nadeem A, Tilley S, et al. Involvement of A1 adenosine receptors in altered vascular responses and inflammation in an allergic mouse model of asthma. Am J Physiol Heart Circ Physiol 2010;299:H81-7
25. Ethier MF, Madison JM. Adenosine A1 receptors mediate mobilization of calcium in human bronchial smooth muscle cells. Am J Respir Cell Mol Biol 2006;35:496-502 (Pubitemid 44477650)
26. Wilson CN. Adenosine receptors and asthma in humans. Br J Pharmacol 2008;155:475-86
27. Press NJ, Gessi S, Borea PA, et al. Therapeutic potential of adenosine receptor antagonists and agonists. Expert Opin Ther Patent 2007;17:979-91 (Pubitemid 47342747)
28. Sun CX, Young HW, Molina JG, et al. A protective role for the A1 adenosine receptor in adenosine-dependent pulmonary injury. J Clin Invest 2005;115:35-43 (Pubitemid 40385503)
29. Ngamsri KC, Wagner R, Vollmer I, et al. Adenosine receptor A1 regulates polymorphonuclear cell trafficking and microvascular permeability in lipopolysaccharide-induced lung injury. J Immunol 2010;185:4374-84
30. Gazoni LM, Walters DM, Unger EB, et al. Activation of A1, A2A, or A3 adenosine receptors attenuates lung ischemia-reperfusion injury. J Thorac Cardiovasc Surg 2010;140:440-6
31. Koeppen M, Eckle T, Eltzschig HK. Selective deletion of the A1 adenosine receptor abolishes heart-rate slowing effects of intravascular adenosine in vivo. PLoS One 2009;4:e6784
32. Schutte F, Burgdorf C, Richardt G, et al. Adenosine A1 receptor-mediated inhibition of myocardial norepinephrine release involves neither phospholipase C nor protein kinase C but does involve adenylyl cyclase. Can J Physiol Pharmacol 2006;84:573-7 (Pubitemid 44350532)
33. Shneyvays V, Leshem D, Zinman T, et al. Role of adenosine A1 and A3 receptors in regulation of cardiomyocyte homeostasis after mitochondrial respiratory chain injury. Am J Physiol Heart Circ Physiol 2005;288:H2792-801 (Pubitemid 40720660)
34. Solenkova NV, Solodushko V, Cohen MV, et al. Endogenous adenosine protects preconditioned heart during early minutes of reperfusion by activating Akt. Am J Physiol Heart Circ Physiol 2006;290:H441-9
35. Yldiz G, Demiryurek AT, Gumusel B, et al. Ischemic preconditioning modulates ischemia-reperfusion injury in the rat lung: role of adenosine receptors. Eur J Pharmacol 2007;556:144-50 (Pubitemid 46074007)
36. Grenz A, Zhang H, Eckle T, et al. Protective role of ecto-5′- nucleotidase (CD73) in renal ischemia. J Am Soc Nephrol 2007;18:833-45 (Pubitemid 46434500)
37. Kiesman WF, Elzein E, Zablocki J. A1 adenosine receptor antagonists, agonists, and allosteric enhancers. In: Wilson CN, Mustafa SJ, editors. Adenosine receptors in health and disease, Handbook of Experimental Pharmacology. Springer-Verlag; Berlin Heidelberg: 2009. p. 25-58
38. Vallon V, Muhlbauer B, Osswald H. Adenosine and kidney function. Physiol Rev 2006;86:901-40 (Pubitemid 44033385)
39. Zhou X, Kost CK. Adenosine A1 receptor antagonist blunts urinary potassium excretion, but not renal hemodynamic effects, induced by carbonic anhydrase inhibitor in rats. J Pharmacol Exp Ther 2006;316:530-8 (Pubitemid 43130978)
40. Sun D, Samuelson LC, Yang T, et al. Mediation of tubuloglomerular feedback by adenosine: evidence from mice lacking adenosine 1 receptors. Proc Natl Acad Sci USA 2001;98:9983-8 (Pubitemid 32769414)
41. Schnermann J, Briggs JP. Tubuloglomerular feedback: mechanistic insights from gene-manipulated mice. Kidney Int 2008;74:418-26
42. Slawsky MT, Givertz MM. Rolofylline: a selective adenosine A1 receptor antagonist for the treatment of heart failure. Expert Opin Pharmacother 2009;10:311-22
43. Weatherley BD, Cotter G, Dittrich HC, et al. PROTECT Steering Committee, Investigators, and Coordinators. Design and rationale of the PROTECT study: a placebo-controlled randomized study of the selective A1 adenosine receptor antagonist Rolofylline for patients hospitalized with acute decompensated heart failure and volume overload to assess treatment effect on congestion and renal function. J Cardiol Fail 2010;16:25-35
44. Voors AA, Dittrich HC, Massie BM, et al. Effects of the Adenosine A(1) Receptor Antagonist Rolofylline on Renal Function in Patients With Acute Heart Failure and Renal Dysfunction Results From PROTECT (Placebo-Controlled Randomized Study of the Selective A(1) Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized With Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function). J Am Coll Cardiol 2011;57:1899-907
45. Hocher B. Adenosine A1 receptor antagonists in clinical research and development. Kidney Int 2010;78:438-45
46. Hocher B, Heiden S, von Websky K, et al. Renal effects of the novel selective adenosine A1 receptor blocker SLV329 in experimental liver cirrhosis in rats. PLoS One 2011;10:e17891
47. Pang PS, Mehra M, Maggioni AP, et al. Rationale, design, and results from RENO-DEFEND 1: a randomized, dose-finding study of the selective A1 adenosine antagonist SLV320 in patients hospitalized with acute heart failure. Am Heart J 2011;161:1012-23.e3
48. Kim M, Chen SW, Park SW, et al. Kidney-specific reconstitution of the A1 adenosine receptor in A1 adenosine receptor knockout mice reduces renal ischemia-reperfusion injury. Kidney Int 2009;75:809-23
49. Chen SW, Park SW, Kim M, et al. Human heat shock protein 27 overexpressing mice are protected against hepatic ischemia and reperfusion injury. Transplantation 2009;87:1478-87
50. Kara FM, Chitu V, Sloane J, et al. Adenosine A1 receptors (A1Rs) play a critical role in osteoclast formation and function. FASEB J 2010;24:2325-33
51. Kara FM, Doty SB, Boskey A, et al. Adenosine A(1) receptors regulate bone resorption in mice: adenosine A(1) receptor blockade or deletion increases bone density and prevents ovariectomy-induced bone loss in adenosine A(1) receptor-knockout mice. Arthritis Rheum 2010;62:534-41
52. Dhalla AK, Melissa S, Smith M, et al. Antilipolytic activity of a novel partial A1 adenosine receptor agonist devoid of cardiovascular effects: comparison with nicotinic acid. J Pharmacol Exp Ther 2007;321:327-33 (Pubitemid 46456970)
53. Dhalla AK, Wong MY, Voshol PJ, et al. A1-adenosine receptor partial agonist lowers plasma FFA and improves insulin resistance induced by high-fat diet in rodents. Am J Physiol Endocrinol Metab 2007;292:E1358-63 (Pubitemid 46684605)
54. Fatholahi M, Xiang Y, Wu Y, et al. A novel partial agonist of the A1-adenosine receptor and evidence of receptor homogeneity in adipocytes. J Pharmacol Exp Ther 2006;317:676-84
55. Shearer J, Severson DL, Su L, et al. Partial A1 adenosine receptor agonist regulates cardiac substrate utilization in insulin-resistant rats in vivo. J Pharmacol Exp Ther 2009;328:306-11
56. Hasko G, Pacher P. A2A receptors in inflammation and injury: lessons learned from transgenic animals. J Leukoc Biol 2008;83:447-55 (Pubitemid 351966849)
57. Sun CN, Cheng HC, Chou JL, et al. Rescue of p53 blockage by the A2A adenosine receptor via a novel interacting protein, translin-associated protein X. Mol Pharmacol 2006;70:454-66
58. Lebon G, Warne T, Edwards PC, et al. Agonist-bound adenosine A(2A) receptor structures reveal common features of GPCR activation. Nature 2011;474:521-5
59. Jenner P, Mori A, Hauser R, et al. Adenosine, adenosine A2A antagonists, and Parkinson's disease. Parkinsonism Relat Disord 2009;15:406-13
60. Varani K, Bachoud-Levi AC, Mariotti C, et al. Biological abnormalities of peripheral A(2A) receptors in a large representation of polyglutamine disorders and Huntington's disease stages. Neurobiol Dis 2007;27:36-43 (Pubitemid 46924865)
61. Simola N, Morelli M, Pinna A. Adenosine A2A receptor antagonists and Parkinson's disease: state of the art and future directions. Curr Pharm Des 2008;14:1475-89 (Pubitemid 351997813)
62. LeWitt PA, Guttman M, Tetrud JW, et al. Adenosine A2A receptor antagonist istradefylline (KW-6002) reduces "off" time in Parkinson's disease: a double-blind, randomized, multicenter clinical trial (6002-US-005). Ann Neurol 2008;63:295-302 (Pubitemid 351499859)
63. Ramlackhansingh AF, Bose SK, Ahmed I, et al. Adenosine 2A receptor availability in dyskinetic and nondyskinetic patients with Parkinson disease. Neurology 2011;76:1811-16
64. Varani K, Vincenzi F, Tosi A, et al. A2A adenosine receptor overexpression and functionality, as well as TNF-alpha levels, correlate with motor symptoms in Parkinson's disease. FASEB J 2010;24:587-98
65. Cavalcante JL, Barboza J, Ananthasubramaniam K. Regadenoson is a safe and well-tolerated pharmacological stress agent for myocardial perfusion imaging in post-heart transplant patients. J Nucl Cardiol 2011;18:628-33
66. Kern MJ, Hodgson JM, Dib N, et al. Effects of apadenoson, a selective adenosine A2A receptor agonist for myocardial perfusion imaging, on coronary blood flow velocity in conscious patients. Circulation 2006;114:(Abstract)2780
67. Bayes M. Gateways to clinical trials. Methods Find Exp Clin Pharmacol 2007;29:153-73 (Pubitemid 46797631)
68. Belardinelli L, Shryock JC, Snowdy S, et al. The A2A adenosine receptor mediates coronary vasodilation. J Pharmacol Exp Ther 1998;284:1066-73 (Pubitemid 28130836)
69. Varani K, Portaluppi F, Gessi S, et al. Dose and time effects of caffeine intake on human platelet adenosine A(2A) receptors: functional and biochemical aspects. Circulation 2000;102:285-9 (Pubitemid 30457577)
70. Gessi S, Varani K, Merighi S, et al. A2A adenosine receptors in human peripheral blood cells. Br J Pharmacol 2000;129:2-11 (Pubitemid 30072665)
71. Blackburn MR, Vance CO, Morschl E, et al. Adenosine receptors and inflammation. Handb Exp Pharmacol 2009;193:215-69
72. Bingham TC, Fisher EA, Parathath S, et al. A2A adenosine receptor stimulation decreases foam cell formation by enhancing ABCA1-dependent cholesterol efflux. J Leukoc Biol 2010;87:683-90
73. Ohta A, Sitkovsky M. The adenosinergic immunomodulatory drugs. Curr Opin Pharmacol 2009;9:501-6
74. McColl SR, St-Onge M, Dussault AA, et al. Immunomodulatory impact of the A2A adenosine receptor on the profile of chemokines produced by neutrophils. FASEB J 2006;20:187-9 (Pubitemid 43100509)
75. Naganuma M, Wiznerowicz EB, Lappas CM, et al. Cutting edge: Critical role for A2A adenosine receptors in the T cell-mediated regulation of colitis. J Immunol 2006;177:2765-9 (Pubitemid 44277790)
76. Sevigny CP, Li L, Awad AS, et al. Activation of adenosine A2A receptors attenuates allograft rejection and alloantigen recognition. J Immunol 2007;178:4240-9 (Pubitemid 46492374)
77. Deaglio S, Dwyer KM, Gao W, et al. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J Exp Med 2007;204:1257-65 (Pubitemid 46919862)
78. Borsellino G, Kleinewietfeld M, Di Mitri D, et al. Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression. Blood 2007;110:1225-32 (Pubitemid 47281420)
79. Himer L, Csoka B, Selmeczy Z, et al. Adenosine A2A receptor activation protects CD4+ T lymphocytes against activation-induced cell death. FASEB J 2010;24:2631-40
80. Ahmad A, Ahmad S, Glover L, et al. Adenosine A2A receptor is a unique angiogenic target of HIF-2alpha in pulmonary endothelial cells. Proc Natl Acad Sci USA 2009;106:10684-9
81. Ernens I, Leonard F, Vausort M, et al. Adenosine up-regulates vascular endothelial growth factor in human macrophages. Biochem Biophys Res Commun 2010;392:351-6
82. Montesinos MC, Desai A, Cronstein BN. Suppression of inflammation by low-dose methotrexate is mediated by adenosine A2A receptor but not A3 receptor activation in thioglycollate-induced peritonitis. Arthritis Res Ther 2006;8:R53
83. Chan ES, Cronstein BN. Methotrexate-how does it really work? Nat Rev Rheumatol 2010;6:175-8
84. Varani K, Massara A, Vincenzi F, et al. Normalization of A2A and A3 adenosine receptor up-regulation in rheumatoid arthritis patients by treatment with anti-tumor necrosis factor alpha but not methotrexate. Arthritis Rheum 2009;60:2880-91
85. Sitkovsky MV, Lukashev D, Apasov S, et al. Physiological control of immune response and inflammatory tissue damage by hypoxia-inducible factors and adenosine A2A receptors. Annu Rev Immunol 2004;22:657-82 (Pubitemid 38680437)
86. Sitkovsky MV. T regulatory cells: hypoxia-adenosinergic suppression and re-direction of the immune response. Trends Immunol 2009;30:102-8
87. Koizumi S, Odashima M, Otaka M, et al. Attenuation of gastric mucosal inflammation induced by indomethacin through activation of the A2A adenosine receptor in rats. J Gastroenterol 2009;44:419-25
88. Polosa R, Blackburn MR. Adenosine receptors as targets for therapeutic intervention in asthma and chronic obstructive pulmonary disease. Trends Pharmacol Sci 2009;30:528-35
89. Mohsenin A, Mi T, Xia Y, et al. Genetic removal of the A2A adenosine receptor enhances pulmonary inflammation, mucin production, and angiogenesis in adenosine deaminase-deficient mice. Am J Physiol Lung Cell Mol Physiol 2007;293:753-61
90. Wallace KL, Linden J. Adenosine A2A receptors induced on iNKT and NK cells reduce pulmonary inflammation and injury in mice with sickle cell disease. Blood 2010;116:5010-20
91. Varani K, Caramori G, Vincenzi F, et al. Alteration of adenosine receptors in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2006;173:398-406 (Pubitemid 43228327)
92. Kong T, Westerman KA, Faigle M, et al. HIF-dependent induction of adenosine A2B receptor in hypoxia. FASEB J 2006;20:2242-50 (Pubitemid 44953854)
93. Yang M, Ma C, Liu S, et al. HIF-dependent induction of adenosine receptor A2B skews human dendritic cells to a Th2-stimulating phenotype under hypoxia. Immunol Cell Biol 2010;88:165-71
94. Gessi S, Fogli E, Sacchetto V, et al. Adenosine modulates HIF-1alpha, VEGF, IL-8, and foam cell formation in a human model of hypoxic foam cells. Arterioscler Thromb Vasc Biol 2010;30:90-7
95. Cohen MV, Yang X, Downey JM. A2B adenosine receptors can change their spots. Br J Pharmacol 2010;159:1595-7
96. Feoktistov I, Biaggioni I. Adenosine A2B receptors evoke interleukin-8 secretion in human mast cells. An enprofyllinesensitive mechanism with implications for asthma. J Clin Invest 1995;96:1979-86
97. Hasko G, Pacher P, Vizi ES, et al. Adenosine receptor signaling in the brain immune system. Trends Pharmacol Sci 2005;26:511-16 (Pubitemid 41338561)
98. Feng MG, Navar LG. Afferent arteriolar vasodilator effect of adenosine predominantly involves adenosine A2B receptor activation. Am J Physiol Renal Physiol 2010;299:F310-15
99. Rajagopal M, Pao AC. Adenosine activates A2B receptors and enhances chloride secretion in kidney inner medullary collecting duct cells. Hypertension 2010;55:1123-8
100. Wakeno M, Minamino T, Seguchi O, et al. Long-term stimulation of adenosine A2B receptors begun after myocardial infarction prevents cardiac remodeling in rats. Circulation 2006;114:1923-32 (Pubitemid 44665386)
101. Philipp S, Yang XM, Cui L, et al. Postconditioning protects rabbit hearts through a protein kinase C-adenosine A2B receptor cascade. Cardiovasc Res 2006;70:308-14
102. Kuno A, Critz SD, Cui L, et al. Protein kinase C protects preconditioned rabbit hearts by increasing sensitivity of adenosine A2B-dependent signaling during early reperfusion. J Mol Cell Cardiol 2007;43:262-71 (Pubitemid 47315714)
103. Kuno A, Solenkova NV, Solodushko V, et al. Infarct limitation by a protein kinase G activator at reperfusion in rabbit hearts is dependent on sensitizing the heart to A2B agonists by protein kinase C. Am J Physiol Heart Circ Physiol 2008;295:H1288-95
104. Methner C, Schmidt K, Cohen MV, et al. Both A2A and A2B adenosine receptors at reperfusion are necessary to reduce infarct size in mouse hearts. Am J Physiol Heart Circ Physiol 2010;299:H1262-4
105. Koda K, Salazar-Rodriguez M, Corti F, et al. Aldehyde dehydrogenase activation prevents reperfusion arrhythmias by inhibiting local renin release from cardiac mast cells. Circulation 2010;122:771-81
106. Yang D, Chen H, Koupenova M, et al. A new role for the A2B adenosine receptor in regulating platelet function. J Thromb Haemost 2010;8:817-27
107. Strohmeier GR, Reppert SM, Lencer WI, et al. The A2B adenosine receptor mediates cAMP responses to adenosine receptor agonists in human intestinal epithelia. J Biol Chem 1995;270:2387-94
108. Ham M, Mizumori M, Watanabe C, et al. Endogenous luminal surface adenosine signaling regulates duodenal bicarbonate secretion in rats. J Pharmacol Exp Ther 2010;335:607-13
109. Sitaraman SV, Merlin D, Wang L, et al. Neutrophil-epithelial crosstalk at the intestinal lumenal surface mediated by reciprocal secretion of adenosine and IL-6. J Clin Invest 2001;107:861-9 (Pubitemid 32274039)
110. Kolachala VL, Wang L, Obertone TS, et al. Adenosine 2B receptor expression is post-transcriptionally regulated by microRNA. J Biol Chem 2010;285:18184-90
111. Kolachala VL, Vijay-Kumar M, Dalmasso G, et al. A2B adenosine receptor gene deletion attenuates murine colitis. Gastroenterology 2008;135:861-70
112. Frick JS, MacManus CF, Scully M, et al. Contribution of adenosine A2B receptors to inflammatory parameters of experimental colitis. J Immunol 2009;182:4957-64
113. Eltzschig HK, Rivera-Nieves J, Colgan SP. Targeting the A2B adenosine receptor during gastrointestinal ischemia and inflammation. Expert Opin Ther Targets 2009;13:1267-77
114. Hasko G, Csoka B, Nemeth ZH, et al. A (2B) adenosine receptors in immunity and inflammation. Trends Immunol 2009;30:263-70
115. Ben Addi A, Lefort A, Hua X, et al. Modulation of murine dendritic cell function by adenine nucleotides and adenosine: involvement of the A2B receptor. Eur J Immunol 2008;38:1610-20
116. Novitskiy SV, Ryzhov S, Zaynagetdinov R, et al. Adenosine receptors in regulation of dendritic cell differentiation and function. Blood 2008;112:1822-31
117. Feoktistov I, Polosa R, Volgate ST, et al. Adenosine A2B receptors: a novel therapeutic target in asthma? Trends Pharmacol Sci 1998;19:148-53 (Pubitemid 28218538)
118. Sun CX, Zhong H, Mohsenin A, et al. Role of A2B adenosine receptor signaling in adenosine-dependent pulmonary inflammation and injury. J Clin Invest 2006;116:2173-82 (Pubitemid 44162326)
119. Yang D, Zhang Y, Nguyen HG, et al. The A2B adenosine receptor protects against inflammation and excessive vascular adhesion. J Clin Invest 2006;116:1913-23 (Pubitemid 44033315)
120. Schingnitz U, Hartmann K, Macmanus CF, et al. Signaling through the A2B adenosine receptor dampens endotoxin-induced acute lung injury. J Immunol 2010;184:5271-9
121. Allen-Gipson DS, Blackburn MR, Schneider DJ, et al. Adenosine activation of A2B Receptor(s) is essential for stimulated epithelial ciliary motility and clearance. Am J Physiol Lung Cell Mol Physiol 2011;301:L171-80
122. Sun J, Zhang Y, Yang M, et al. Hypoxia induces T-cell apoptosis by inhibiting chemokine C receptor 7 expression: the role of adenosine receptor A2. Cell Mol Immunol 2010;7:77-82
123. Baraldi PG, Borea PA. New potent and selective human adenosine A(3) receptor antagonists. Trends Pharmacol Sci 2000;21:456-9
124. Raman M, Chen W, Cobb MH. Differential regulation and properties of MAPKs. Oncogene 2007;26:3100-12 (Pubitemid 46763006)
125. Jacobson KA. Adenosine A3 receptors: novel ligands and paradoxical effects. Trends Pharmacol Sci 1998;19:184-91 (Pubitemid 28255405)
126. Fedorova IM, Jacobson MA, Basile QA, et al. Behavioral characterization of mice lacking the A3 adenosine receptor: sensitivity to hypoxic neurodegeneration. Cell Mol Neurobiol 2003;23:431-47 (Pubitemid 36676284)
127. Ge ZD, Peart JN, Kreckler LM, et al. Cl-IB-MECA [2-chloro-N6-(3- iodobenzyl)adenosine-5′-Nmethylcarboxamide] reduces ischemia/reperfusion injury in mice by activating the A3 adenosine receptor. J Pharmacol Exp Ther 2006;319:1200-10
128. Black RG, Guo Y, Ge ZD, et al. Gene dosage-dependent effects of cardiac-specific overexpression of the A3 adenosine receptor. Circ Res 2002;91:165-72 (Pubitemid 34827228)
129. Funakoshi H, Chan TO, Good JC, et al. Regulated overexpression of the A1-adenosine receptor in mice results in adverse but reversible changes in cardiac morphology and function. Circulation 2006;114:2240-50 (Pubitemid 44789499)
130. Karjian P, Al-Rajaibi H, Hussain A, et al. Activation of A3 adenosine receptors protects the ischemic reperfused myocardium via recruitment of PI3K-AKT-iNOS cell survival pathway. Circulation 2006;114:II-1204
131. Karjian P, Al-Rajaibi H, Hussain A, et al. A3 adenosine receptor activation via 2-Cl-IBMECA protects the myocardium via recruitment of PI3K-AKT-iNOS intracellular signalling pathway during reperfusion. J Mol Cell Cardiol 2008;44:738
132. Hussain A, Karjian P, Maddock H. The role of nitric oxide in A3 adenosine receptor-mediated cardioprotection. Auton Autacoid Pharmacol 2009;29:97-104
133. Zhou R, Chen F, Li Q, et al. Stimulation of the adenosine A3 receptor reverses vascular hyporeactivity after hemorrhagic shock in rats. Acta Pharmacol Sin 2010;31:413-20
134. Gessi S, Varani K, Merighi S, et al. A3 adenosine receptors in human neutrophils and promyelocytic HL60 cells: a pharmacological and biochemical study. Mol Pharmacol 2002;61:415-24 (Pubitemid 34112817)
135. Chen Y, Corriden R, Inoue Y, et al. ATP release guides neutrophil chemotaxis via P2Y2 and A3 receptors. Science 2006;314:1792-5 (Pubitemid 44969094)
136. Linden J. Cell biology. Purinergic chemotaxis. Science 2006;314:1689-90
137. Morschl E, Molina JG, Volmer JB, et al. A3 adenosine receptor signaling influences pulmonary inflammation and fibrosis. Am J Respir Cell Mol Biol 2008;39:697-705
138. Brown RA, Spina D, Page CP. Adenosine receptors and asthma. Br J Pharmacol 2008;153:S446-56 (Pubitemid 351341018)
139. Gessi S, Merighi S, Varani K, et al. The A3 adenosine receptor: an enigmatic player in cell biology. Pharmacol Ther 2008;117:123-40 (Pubitemid 350192673)
140. Merighi S, Mirandola P, Varani K, et al. A glance at adenosine receptors: novel target for antitumor therapy. Pharmacol Ther 2003;100:31-48 (Pubitemid 37204899)
141. Merighi S, Benini A, Mirandola P, et al. A3 adenosine receptor activation inhibits cell proliferation via phosphatidylinositol 3-kinase/Akt-dependent inhibition of the extracellular signal-regulated kinase 1/2 phosphorylation in A375 human melanoma cells. J Biol Chem 2005;280:19516-26 (Pubitemid 41379472)
142. Kim H, Kang JW, Lee S, et al. A3 adenosine receptor antagonist, truncated Thio-Cl-IB-MECA, induces apoptosis in T24 human bladder cancer cells. Anticancer Res 2010;30:2823-30
143. Gessi S, Merighi S, Varani K, et al. Adenosine receptors in colon carcinoma tissues and colon tumoral cell lines: focus on the A3 adenosine subtype. J Cell Physiol 2007;211:826-36 (Pubitemid 46683050)
144. Taliani S, La Motta C, Mugnaini L, et al. Novel N2-substituted pyrazolo[3,4-d]pyrimidine adenosine A3 receptor antagonists: inhibition of A3-mediated human glioblastoma cell proliferation. J Med Chem 2010;53:3954-63
145. Varani K, Maniero S, Vincenzi F, et al. A3 Receptors are overexpressed in Pleura from Mesothelioma patients and reduce cell growth via Akt/NF-kB pathway. Am J Respir Crit Care Med 2011;183:522-30
146. Fishman P, Bar-Yehuda S, Ohana G, et al. An agonist to the A3 adenosine receptor inhibits colon carcinoma growth in mice via modulation of GSK-3 beta and NF-kappa B. Oncogene 2004;23:2465-71 (Pubitemid 38520744)
147. Merighi S, Benini A, Mirandola P, et al. A3 adenosine receptors modulate hypoxia-inducible factor-1alpha expression in human A375 melanoma cells. Neoplasia 2005;7:894-903
148. Merighi S, Benini A, Mirandola P, et al. Adenosine modulates vascular endothelial growth factor expression via hypoxia-inducible factor-1 in human glioblastoma cells. Biochem Pharmacol 2006;72:19-31 (Pubitemid 43795348)
149. Merighi S, Benini A, Mirandola P, et al. Hypoxia inhibits paclitaxel-induced apoptosis through adenosine-mediated phosphorylation of bad in glioblastoma cells. Mol Pharmacol 2007;72:162-72 (Pubitemid 46998535)
150. Merighi S, Benini A, Mirandola P, et al. Caffeine inhibits adenosine-induced accumulation of hypoxia-inducible factor-1alpha, vascular endothelial growth factor, and interleukin-8 expression in hypoxic human colon cancer cells. Mol Pharmacol 2007;72:395-406 (Pubitemid 47124120)
151. Merighi S, Simioni C, Gessi S, et al. A2B and A3 adenosine receptors modulate vascular endothelial growth factor and interleukin-8 expression in human melanoma cells treated with etoposide and doxorubicin. Neoplasia 2009;11:1064-73
152. Gessi S, Cattabriga E, Avitabile A, et al. Elevated expression of A3 adenosine receptors in human colorectal cancer is reflected in peripheral blood cells. Clin Cancer Res 2004;10:5895-901 (Pubitemid 39180971)
153. Gessi S, Varani K, Merighi S, et al. Expression of A3 adenosine receptors in human lymphocytes: up-regulation in T cell activation. Mol Pharmacol 2004;65:711-19 (Pubitemid 38264039)
154. Bar-Yehuda S, Stemmer SM, Madi L, et al. The A3 adenosine receptor agonist CF102 induces apoptosis of hepatocellular carcinoma via de-regulation of the Wnt and NF-kappaB signal transduction pathways. Int J Oncol 2008;33:287-95
155. Jajoo S, Mukherjea D, Watabe K, et al. Adenosine A3 receptor suppresses prostate cancer metastasis by inhibiting NADPH oxidase activity. Neoplasia 2009;11:1132-45
156. Gessi S, Sacchetto V, Fogli E, et al. Modulation of metalloproteinase-9 in U87MG glioblastoma cells by A3 adenosine receptors. Biochem Pharmacol 2010;79:1483-95
157. Fishman P, Bar-Yehuda S, Synowitz M, et al. Adenosine receptors and cancer. Handb Exp Pharmacol 2009;193:399-41
158. Gessi S, Merighi S, Sacchetto V, et al. Adenosine receptors and cancer. Biochim Biophys Acta 2010;30:90-7
159. Fishman P, Bar-Yehuda S, Madi L, et al. The PI3K-NF-kappaB signal transduction pathway is involved in mediating the anti-inflammatory effect of IB-MECA in adjuvant-induced arthritis. Arthritis Res Ther 2006;8:R33
160. Sajjadi FG, Takabayashi K, Foster AC, et al. Inhibition of TNF-alpha expression by adenosine. Role of A3 receptors. J Immunol 1996;156:3435-42 (Pubitemid 26124449)
161. Lee JY, Jhun BS, Oh YT, et al. Activation of adenosine A3 receptor suppresses lipopolysaccaride-induced TNF-alpha production through inhibition of PI-3-kinase/Akt and NF-kappaB activation in murine BV2 microglial cells. Neurosci Lett 2006;396:1-6 (Pubitemid 43233777)
162. Salvatore CA, Tilley SL, Latour AM, et al. Disruption of the A3 adenosine receptor gene in mice and its effect on stimulated inflammatory cells. J Biol Chem 2000;275:4429-34 (Pubitemid 30094686)
163. Martin L, Pingle SC, Hallam DM, et al. Activation of the adenosine A3 receptor in RAW 264.7 cells inhibits lipopolysaccharide-stimulated tumor necrosis factor-alpha release by reducing calcium-dependent activation of nuclear factor-kB and extracellular signal-regulated kinase 1/2. J Pharmacol Exp Ther 2006;316:71-8 (Pubitemid 41832582)
164. Kreckler LM, Wan TC, Ge ZD, et al. Adenosine inhibits tumor necrosis factor-alpha release from mouse peritoneal macrophages via A2A and A2B but not the A3 adenosine receptor. J Pharmacol Exp Ther 2006;317:172-80
165. Hasko G, Pacher P, Deitch EA, et al. Shaping of monocyte and macrophage function by adenosine receptors. Pharmacol Ther 2007;113:264-75 (Pubitemid 46149045)
166. Madi L, Cohen S, Ochaion A, et al. Overexpression of A3 adenosine receptor in peripheral blood mononuclear cells in rheumatoid arthritis: involvement of nuclear factor-kappaB in mediating receptor level. J Rheumatol 2007;34:20-6 (Pubitemid 46106558)
167. Lee HT, Kim M, Joo JD, et al. A3 adenosine receptor activation decreases mortality and renal and hepatic injury in murine septic peritonitis. Am J Physiol Regul Integr Comp Physiol 2006;291:R959-69 (Pubitemid 44498436)
168. Inoue Y, Tanaka H, Sumi Y, et al. A3 adenosine receptor inhibition improves the efficacy of hypertonic saline resuscitation. Shock 2010;35:178-83
169. Matot I, Weiniger CF, Zeira E, et al. A3 adenosine receptors and mitogen-activated protein kinases in lung injury following in vivo reperfusion. Crit Care 2006;10:R65
170. Yang H, Avila MY, Peterson-Yantorno K, et al. The cross-species A3 adenosine-receptor antagonist MRS 1292 inhibits adenosine-triggered human nonpigmented ciliary epithelial cell fluid release and reduces mouse intraocular pressure. Curr Eye Res 2005;30:747-54 (Pubitemid 41426501)
171. Wang Z, Do CW, Avila MY, et al. Nucleoside-derived antagonists to A3 adenosine receptors lower mouse intraocular pressure and act across species. Exp Eye Res 2010;90:146-54
172. Zhang M, Budak MT, Lu W, et al. Identification of the A3 adenosine receptor in rat retinal ganglion cells. Mol Vis 2006;12:937-48
173. Zhang X, Zhang M, Laties AM, et al. Balance of purines may determine life or death of retinal ganglion cells as A3 adenosine receptors prevent loss following P2X7 receptor stimulation. J Neurochem 2006;98:566-75 (Pubitemid 44133159)
174. Zhang M, Hu H, Zhang X, et al. The A3 adenosine receptor attenuates the calcium rise triggered by NMDA receptors in retinal ganglion cells. Neurochem Int 2010;56:35-41
175. Hu H, Lu W, Zhang M, et al. Stimulation of the P2X7 receptor kills rat retinal ganglion cells in vivo. Exp Eye Res 2010;91:425-32
176. Avni I, Garzozi HJ, Barequet IS, et al. Treatment of dry eye syndrome with orally administered CF101: data from a phase 2 clinical trial. Ophthalmology 2010;117:1287-93
177. Varani K, Merighi S, Gessi S, et al. [3H] MRE 3008F20: a novel antagonist radioligand for the pharmacological and biochemical characterization of human A3 adenosine receptors. Mol Pharmacol 2000;57:968-75 (Pubitemid 30253381)
178. Gessi S, Varani K, Merighi S, et al. Expression, pharmacological profile, and functional coupling of A2B receptors in a recombinant system and in peripheral blood cells using a novel selective antagonist radioligand, [3H]MRE 2029-F20. Mol Pharmacol 2005;67:2137-47 (Pubitemid 41014812)