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Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Role and Function of Adenosine and its Receptors in Inflammation, Neuroinflammation, IBS, Autoimmune Inflammatory Disorders, Rheumatoid Arthritis and Psoriasis

Author(s): Ashok K. Shakya*, Rajashri R. Naik, Ihab M. ALMASRI and Avneet Kaur

Volume 25 , Issue 26 , 2019

Page: [2875 - 2891] Pages: 17

DOI: 10.2174/1381612825666190716145206

Price: $65


The physiological effects of endogenous adenosine on various organ systems are very complex and numerous which are elicited upon activation of any of the four G-protein-coupled receptors (GPCRs) denoted as A1, A2A, A2B and A3 adenosine receptors (ARs). Several fused heterocyclic and non-xanthine derivatives are reported as a possible target for these receptors due to physiological problems and lack of selectivity of xanthine derivatives. In the present review, we have discussed the development of various new chemical entities as a target for these receptors. In addition, compounds acting on adenosine receptors can be utilized in treating diseases like inflammation, neuroinflammation, autoimmune and related diseases.

Keywords: A1, A2A, A2B and A3, adenosine receptors, GPCR, inflammation, irritable bowel syndrome, neuroinflammation.

Burnstock G. Purines-2014: Nucleotides, nucleosides and nucleobases - international conference on signaling, drugs and targets. Purinergic Signal 2014; 10: 657-854.
Yegutkin GG. Nucleotide- and nucleoside-converting ectoenzymes: Important modulators of purinergic signalling cascade. Biochim Biophys Acta 2008; 1783(5): 673-94.
[] [PMID: 18302942]
Haskó G, Sitkovsky MV, Szabó C. Immunomodulatory and neuroprotective effects of inosine. Trends Pharmacol Sci 2004; 25(3): 152-7.
[] [PMID: 15019271]
Haskó G, Cronstein BN. Adenosine: An endogenous regulator of innate immunity. Trends Immunol 2004; 25(1): 33-9.
[] [PMID: 14698282]
Antonioli L, Colucci R, Pellegrini C, et al. The AMPK enzyme-complex: From the regulation of cellular energy homeostasis to a possible new molecular target in the management of chronic inflammatory disorders. Expert Opin Ther Targets 2016; 20(2): 179-91.
[] [PMID: 26414111]
Gessi S, Merighi S, Varani K, Leung E, Mac Lennan S, Borea PA. The A3 adenosine receptor: An enigmatic player in cell biology. Pharmacol Ther 2008; 117(1): 123-40.
[] [PMID: 18029023]
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(10): 2880-91.
[] [PMID: 19790066]
Hansen BD, Chiang PK, Perez-Arbelo J. Evidence for a membrane adenosine receptor in Leishmania mexicana mexicana (WR 227) Purine and Pyrimidine Metabolism in Man V. Boston, MA: Springer 1986; pp. 547-51.
Dolezelova E, Nothacker HP, Civelli O, Bryant PJ, Zurovec M. A Drosophila adenosine receptor activates cAMP and calcium signaling. Insect Biochem Mol Biol 2007; 37(4): 318-29.
[] [PMID: 17368195]
Barraco RA, Stefano GB. Pharmacological evidence for the modulation of monoamine release by adenosine in the invertebrate nervous system. J Neurochem 1990; 54(6): 2002-6.
[] [PMID: 2338553]
Jacobson KA, Gao ZG. Adenosine receptors as therapeutic targets. Nat Rev Drug Discov 2006; 5(3): 247-64.
[] [PMID: 16518376]
Fredholm BB, IJzerman AP, Jacobson KA, Klotz KN, Linden J. International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacol Rev 2001; 53(4): 527-52.
[PMID: 11734617]
Eltzschig HK, Macmanus CF, Colgan SP. Neutrophils as sources of extracellular nucleotides: Functional consequences at the vascular interface. Trends Cardiovasc Med 2008; 18(3): 103-7.
[] [PMID: 18436149]
Kaku H, Cheng KF, Al-Abed Y, Rothstein TL. A novel mechanism of B cell-mediated immune suppression through CD73 expression and adenosine production. J Immunol 2014; 193(12): 5904-13.
[] [PMID: 25392527]
Michael S, Warstat C, Michel F, Yan L, Müller CE, Nieber K. Adenosine A(2A) agonist and A(2B) antagonist mediate an inhibition of inflammation-induced contractile disturbance of a rat gastrointestinal preparation. Purinergic Signal 2010; 6(1): 117-24.
[] [PMID: 20020217]
Jockers R, Linder ME, Hohenegger M, et al. Species difference in the G protein selectivity of the human and bovine A1-adenosine receptor. J Biol Chem 1994; 269(51): 32077-84.
[PMID: 7798201]
Palmer TM, Gettys TW, Stiles GL. Differential interaction with and regulation of multiple G-proteins by the rat A3 adenosine receptor. J Biol Chem 1995; 270(28): 16895-902.
[] [PMID: 7622506]
Freund S, Ungerer M, Lohse MJ A A. 1 adenosine receptors expressed in CHO-cells couple to adenylyl cyclase and to phospholipase C. N-S Arch Pharmacol 1994; 350(1): 49-56.
Zhou QY, Li C, Olah ME, Johnson RA, Stiles GL, Civelli O. Molecular cloning and characterization of an adenosine receptor: The A3 adenosine receptor. Proc Natl Acad Sci USA 1992; 89(16): 7432-6.
[] [PMID: 1323836]
Boyle DL, Sajjadi FG, Firestein GS. Inhibition of synoviocyte collagenase gene expression by adenosine receptor stimulation. Arthritis Rheum 1996; 39(6): 923-30.
[] [PMID: 8651985]
Haskó G, Szabó C, Németh ZH, Kvetan V, Pastores SM, Vizi ES. Adenosine receptor agonists differentially regulate IL-10, TNF-alpha, and nitric oxide production in RAW 264.7 macrophages and in endotoxemic mice. J Immunol 1996; 157(10): 4634-40.
[PMID: 8906843]
Bouma MG, Stad RK, van den Wildenberg FA, Buurman WA. Differential regulatory effects of adenosine on cytokine release by activated human monocytes. J Immunol 1994; 153(9): 4159-68.
[PMID: 7930619]
Sajjadi FG, Takabayashi K, Foster AC, Domingo RC, Firestein GS. Inhibition of TNF-alpha expression by adenosine: Role of A3 adenosine receptors. J Immunol 1996; 156(9): 3435-42.
[PMID: 8617970]
Le Moine O, Stordeur P, Schandené L, et al. Adenosine enhances IL-10 secretion by human monocytes. J Immunol 1996; 156(11): 4408-14.
[PMID: 8666814]
Schwaninger M, Neher M, Viegas E, Schneider A, Spranger M. Stimulation of interleukin-6 secretion and gene transcription in primary astrocytes by adenosine. J Neurochem 1997; 69(3): 1145-50.
[] [PMID: 9282937]
Schulte G, Fredholm BB. The G(s)-coupled adenosine A(2B) receptor recruits divergent pathways to regulate ERK1/2 and p38. Exp Cell Res 2003; 290(1): 168-76.
[] [PMID: 14516797]
Hirano D, Aoki Y, Ogasawara H, et al. Functional coupling of adenosine A2a receptor to inhibition of the mitogen-activated protein kinase cascade in Chinese hamster ovary cells. Biochem J 1996; 316(Pt 1): 81-6.
[] [PMID: 8645236]
Gessi S, Varani K, Merighi S, Ongini E, Borea PAAA. (2A) adenosine receptors in human peripheral blood cells. Br J Pharmacol 2000; 129(1): 2-11.
[] [PMID: 10694196]
Oyarzún C, Garrido W, Alarcón S, et al. Adenosine contribution to normal renal physiology and chronic kidney disease. Mol Aspects Med 2017; 55: 75-89.
[] [PMID: 28109856]
Peleli M, Carlstrom M. Adenosine signaling in diabetes mellitus and associated cardiovascular and renal complications. Mol Aspects Med 2017; 55: 62-74.
[] [PMID: 28089906]
Burnstock G. Purinergic signaling in the cardiovascular system. Circ Res 2017; 120(1): 207-28.
[] [PMID: 28057794]
Gicquel T, Le Daré B, Boichot E, Lagente V. Purinergic receptors: New targets for the treatment of gout and fibrosis. Fundam Clin Pharmacol 2017; 31(2): 136-46.
[] [PMID: 27885718]
Jacobson KA, Merighi S, Varani K, et al. A3 Adenosine receptors as modulators of inflammation: From medicinal chemistry to therapy. Med Res Rev 2018; 38(4): 1031-72.
[] [PMID: 28682469]
Csóka B, Németh ZH, Duerr CU, Fritz JH, Pacher P, Haskó G. Adenosine receptors differentially regulate type 2 cytokine production by IL-33-activated bone marrow cells, ILC2s, and macrophages. FASEB J 2018; 32(2): 829-37.
[] [PMID: 28982732]
Luan G, Wang X, Gao Q, et al. Upregulation of neuronal adenosine a1 receptor in human rasmussen encephalitis. J Neuropathol Exp Neurol 2017; 76(8): 720-31.
[] [PMID: 28789481]
Cronstein BN, Sitkovsky M. Adenosine and adenosine receptors in the pathogenesis and treatment of rheumatic diseases. Nat Rev Rheumatol 2017; 13(1): 41-51.
[] [PMID: 27829671]
Lemos C, Pinheiro BS, Beleza RO, et al. Adenosine A2B receptor activation stimulates glucose uptake in the mouse forebrain. Purinergic Signal 2015; 11(4): 561-9.
[] [PMID: 26446689]
van Waarde A, Dierckx RAJO, Zhou X, et al. Potential therapeutic applications of adenosine A2a receptor ligands and opportunities for A2A receptor imaging. Med Res Rev 2018; 38(1): 5-56.
[] [PMID: 28128443]
Gessi S, Merighi S, Stefanelli A, Fazzi D, Varani K, Borea PAAA. (1) and A(3) adenosine receptors inhibit LPS-induced hypoxia-inducible factor-1 accumulation in murine astrocytes. Pharmacol Res 2013; 76: 157-70.
[] [PMID: 23969284]
Figueiredo AB, Souza-Testasicca MC, Afonso LCC. Purinergic signaling and infection by Leishmania: A new approach to evasion of the immune response. Biomed J 2016; 39(4): 244-50.
[] [PMID: 27793266]
Fredholm BB, Bättig K, Holmén J, Nehlig A, Zvartau EE. Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol Rev 1999; 51(1): 83-133.
[PMID: 10049999]
Sawynok J, Liu XJ. Adenosine in the spinal cord and periphery: Release and regulation of pain. Prog Neurobiol 2003; 69(5): 313-40.
[] [PMID: 12787573]
Salmon JE, Brogle N, Brownlie C, et al. Human mononuclear phagocytes express adenosine A1 receptors. A novel mechanism for differential regulation of Fc gamma receptor function. J Immunol 1993; 151(5): 2775-85.
[PMID: 8360491]
Rose FR, Hirschhorn R, Weissmann G, Cronstein BN. Adenosine promotes neutrophil chemotaxis. J Exp Med 1988; 167(3): 1186-94.
[] [PMID: 2832507]
Cronstein BN, Levin RI, Philips M, Hirschhorn R, Abramson SB, Weissmann G. Neutrophil adherence to endothelium is enhanced via adenosine A1 receptors and inhibited via adenosine A2 receptors. J Immunol 1992; 148(7): 2201-6.
[PMID: 1347551]
Faulhaber-Walter R, Jou W, Mizel D, et al. Impaired glucose tolerance in the absence of adenosine A1 receptor signaling. Diabetes 2011; 60(10): 2578-87.
[] [PMID: 21831968]
Marzagalli R, Castorina A. The seeming paradox of adenosine receptors as targets for the treatment of Alzheimer’s disease: Agonists or antagonists? Neural Regen Res 2015; 10(2): 205-7.
[] [PMID: 25883615]
Haskó G, Kuhel DG. CHEN JF, Schwarzschild MA, Deitch EA, Mabley JG, Marton A, Szabo C. Adenosine inhibits IL-12 and TNF-α production via adenosine A2A receptor-dependent and independent mechanisms. FASEB J 2000; 14(13): 2065-74.
[] [PMID: 11023991]
Odashima M, Otaka M, Jin M, et al. Attenuation of gastric mucosal inflammation induced by aspirin through activation of A2A adenosine receptor in rats. World J Gastroenterol 2006; 12(4): 568-73.
[] [PMID: 16489670]
Fotheringham JA, Mayne MB, Grant JA, Geiger JD. Activation of adenosine receptors inhibits tumor necrosis factor-α release by decreasing TNF-α mRNA stability and p38 activity. Eur J Pharmacol 2004; 497(1): 87-95.
[] [PMID: 15321739]
McPherson JA, Barringhaus KG, Bishop GG, et al. Adenosine A(2A) receptor stimulation reduces inflammation and neointimal growth in a murine carotid ligation model. Arterioscler Thromb Vasc Biol 2001; 21(5): 791-6.
[] [PMID: 11348876]
Khimenko PL, Moore TM, Hill LW, et al. Adenosine A2 receptors reverse ischemia-reperfusion lung injury independent of beta-receptors. J Appl Physiol 1995; 78(3): 990-6.
[] [PMID: 7775345]
Day YJ, Marshall MA, Huang L, McDuffie MJ, Okusa MD, 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(2): G285-93.
[] [PMID: 14715520]
Okusa MD, Linden J, Macdonald T, Huang L. Selective A2A adenosine receptor activation reduces ischemia-reperfusion injury in rat kidney. Am J Physiol 1999; 277(3): F404-12.
[PMID: 10484524]
Cassada DC, Tribble CG, Long SM, et al. Adenosine A2A analogue ATL-146e reduces systemic tumor necrosing factor-α and spinal cord capillary platelet-endothelial cell adhesion molecule-1 expression after spinal cord ischemia. J Vasc Surg 2002; 35(5): 994-8.
[] [PMID: 12021717]
Dai SS, Zhou YG. Adenosine 2A receptor: A crucial neuromodulator with bidirectional effect in neuroinflammation and brain injury. Rev Neurosci 2011; 22(2): 231-9.
[] [PMID: 21476942]
Chen JF, Huang Z, Ma J, et al. A(2A) adenosine receptor deficiency attenuates brain injury induced by transient focal ischemia in mice. J Neurosci 1999; 19(21): 9192-200.
[] [PMID: 10531422]
Popoli P, Pintor A, Domenici MR, et al. Blockade of striatal adenosine A2A receptor reduces, through a presynaptic mechanism, quinolinic acid-induced excitotoxicity: Possible relevance to neuroprotective interventions in neurodegenerative diseases of the striatum. J Neurosci 2002; 22(5): 1967-75.
[] [PMID: 11880527]
Varano F, Catarzi D, Vincenzi F, et al. Design, synthesis, and pharmacological characterization of 2-(2-furanyl) thiazolo [5, 4-d] pyrimidine-5, 7-diamine derivatives: New highly potent A2A adenosine receptor inverse agonists with antinociceptive activity. J Med Chem 2016; 59(23): 10564-76.
[] [PMID: 27933962]
Fernández-Dueñas V, Azuaje J, Morató X, et al. Synthesis and characterization of a new bivalent ligand combining Caffeine and Docosahexaenoic Acid. Molecules 2017; 22(3): 366.
[] [PMID: 28264466]
Zheng X, Hasegawa H. Administration of caffeine inhibited adenosine receptor agonist-induced decreases in motor performance, thermoregulation, and brain neurotransmitter release in exercising rats. Pharmacol Biochem Behav 2016; 140: 82-9.
[] [PMID: 26604076]
Chandrasekaran B, Deb PK, Kachler S, Akkinepalli RR, Mailavaram R, Klotz KN. Synthesis and adenosine receptors binding studies of new fluorinated analogues of pyrido [2, 3-d] pyrimidines and quinazolines. Med Chem Res 2018; 27(3): 756-67.
Manjunath S, Sakhare PM. Adenosine and adenosine receptors: Newer therapeutic perspective. Indian J Pharmacol 2009; 41(3): 97-105.
[] [PMID: 20442815]
Chen H, Yang D, Carroll SH, Eltzschig HK, Ravid K. Activation of the macrophage A2b adenosine receptor regulates tumor necrosis factor-α levels following vascular injury. Exp Hematol 2009; 37(5): 533-8.
[] [PMID: 19375644]
Sharmin S, Guan H, Williams AS, Yang K. Caffeine reduces 11β-hydroxysteroid dehydrogenase type 2 expression in human trophoblast cells through the adenosine A2B receptor. PLoS One 2012; 7(6)e38082
[] [PMID: 22701600]
Yang D, Zhang Y, Nguyen HG, et al. The A2B adenosine receptor protects against inflammation and excessive vascular adhesion. J Clin Invest 2006; 116(7): 1913-23.
[] [PMID: 16823489]
Feoktistov I, Goldstein AE, Biaggioni I. 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 1999; 55(4): 726-34.
[PMID: 10101031]
Marquardt DL, Walker LL, Heinemann S. Cloning of two adenosine receptor subtypes from mouse bone marrow-derived mast cells. J Immunol 1994; 152(9): 4508-15.
[PMID: 8157966]
Németh ZH, Lutz CS, Csóka B, et al. Adenosine augments IL-10 production by macrophages through an A2B receptor-mediated posttranscriptional mechanism. J Immunol 2005; 175(12): 8260-70.
[] [PMID: 16339566]
Nguyen DK, Montesinos MC, Williams AJ, Kelly M, Cronstein BN. Th1 cytokines regulate adenosine receptors and their downstream signaling elements in human microvascular endothelial cells. J Immunol 2003; 171(8): 3991-8.
[] [PMID: 14530318]
Sun Y, Duan Y, Eisenstein AS, et al. A novel mechanism of control of NFκB activation and inflammation involving A2B adenosine receptors. J Cell Sci 2012; 125(Pt 19): 4507-17.
[] [PMID: 22767505]
Johnston-Cox H, Koupenova M, Yang D, et al. The A2B adenosine receptor modulates glucose homeostasis and obesity. PLoS One 2012; 7(7)e40584
Wojcik M, Zieleniak A, Mac-Marcjanek K, Wozniak LA, Cypryk K. The elevated gene expression level of the A(2B) adenosine receptor is associated with hyperglycemia in women with gestational diabetes mellitus. Diabetes Metab Res Rev 2014; 30(1): 42-53.
[] [PMID: 23956030]
Müller CE, Grahner B, Heber D. Amino-substituted 1,8-naphthyridines and pyrido[2,3-d]pyrimidines: New compounds with affinity for A1- and A2-adenosine receptors. Pharmazie 1994; 49(12): 878-80.
[PMID: 7838877]
Csóka B, Németh ZH, Virág L, et al. A2A adenosine receptors and C/EBPbeta are crucially required for IL-10 production by macrophages exposed to Escherichia coli. Blood 2007; 110(7): 2685-95.
[] [PMID: 17525287]
Wakai A, Wang JH, Winter DC, Street JT, O’Sullivan RG, Redmond HP. Adenosine inhibits neutrophil vascular endothelial growth factor release and transendothelial migration via A2B receptor activation. Shock 2001; 15(4): 297-301.
[] [PMID: 11303729]
Mate A, Vázquez CM, Leiva A, Sobrevía L. New therapeutic approaches to treating hypertension in pregnancy. Drug Discov Today 2012; 17(23-24): 1307-15.
[] [PMID: 22796125]
Harish A, Hohana G, Fishman P, Arnon O, Bar-Yehuda S. A3 adenosine receptor agonist potentiates natural killer cell activity. Int J Oncol 2003; 23(4): 1245-9.
[] [PMID: 12964011]
Gessi S, Varani K, Merighi S, et al. A(3) adenosine receptors in human neutrophils and promyelocytic HL60 cells: A pharmacological and biochemical study. Mol Pharmacol 2002; 61(2): 415-24.
[] [PMID: 11809867]
van der Hoeven D, Wan TC, Auchampach JA. Activation of the A(3) adenosine receptor suppresses superoxide production and chemotaxis of mouse bone marrow neutrophils. Mol Pharmacol 2008; 74(3): 685-96.
[] [PMID: 18583455]
Gao Z, Li BS, Day YJ, Linden J. A3 adenosine receptor activation triggers phosphorylation of protein kinase B and protects rat basophilic leukemia 2H3 mast cells from apoptosis. Mol Pharmacol 2001; 59(1): 76-82.
[] [PMID: 11125027]
Gessi S, Merighi S, Varani K, Borea PA. Adenosine receptors in health and disease. Adv Pharmacol 2011; 61: 41-75.
Tosh DK, Paoletta S, Chen Z, et al. Structure-based design, synthesis by click chemistry and in vivo activity of highly selective A3 adenosine receptor agonists. MedChemComm 2015; 6(4): 555-63.
[] [PMID: 26236460]
Cheong SL, Federico S, Venkatesan G, et al. The A3 adenosine receptor as multifaceted therapeutic target: Pharmacology, medicinal chemistry, and in silico approaches. Med Res Rev 2013; 33(2): 235-335.
[] [PMID: 22095687]
Jacobson KA. Inventors; A3 adenosine receptor antagonists and partial agonist. Aust. Pat. Appl. AU 2009276411 A1 20100204, 2010.
Ciancetta A, Jacobson KA. Structural probing and molecular modeling of the A3 adenosine receptor: A focus on agonist binding. Molecules 2017; 22(3): 449.
[] [PMID: 28287473]
Jacobson KA, Tosh DK. Inventors; US Department of Health, Human Services (HHS), assignee. Methanocarba adenosine derivatives, pharmaceutical compositions, and method of reducing intraocular pressure. United States Patent US 8,518,957, 2013.
Subash S, Essa MM, Al-Adawi S, Memon MA, Manivasagam T, Akbar M. Neuroprotective effects of berry fruits on neurodegenerative diseases. Neural Regen Res 2014; 9(16): 1557-66.
[] [PMID: 25317174]
Lassmann H, Brück W, Lucchinetti C. Heterogeneity of multiple sclerosis pathogenesis: Implications for diagnosis and therapy. Trends Mol Med 2001; 7(3): 115-21.
[] [PMID: 11286782]
Mayne M, Shepel PN, Jiang Y, Geiger JD, Power C. Dysregulation of adenosine A1 receptor-mediated cytokine expression in peripheral blood mononuclear cells from multiple sclerosis patients. Ann Neurol 1999; 45(5): 633-9.
[<633:AID-ANA12>3.0.CO;2-X] [PMID: 10319886]
Johnston JB, Silva C, Gonzalez G, et al. Diminished adenosine A1 receptor expression on macrophages in brain and blood of patients with multiple sclerosis. Ann Neurol 2001; 49(5): 650-8.
[] [PMID: 11357956]
Tsutsui S, Schnermann J, Noorbakhsh F, et al. A1 adenosine receptor upregulation and activation attenuates neuroinflammation and demyelination in a model of multiple sclerosis. J Neurosci 2004; 24(6): 1521-9.
[] [PMID: 14960625]
Lin YL, Chern Y, Fang JM, Lin JH, Huang NK. Inventors; Academia Sinica, assignee. Dual-action compounds targeting adenosine a2a receptor and adenosine transporter for prevention and treatment of neurodegenerative diseases. United States Patent application US 13/508,797, 2012.
Lee JY, Jhun BS, Oh YT, et al. Activation of adenosine A3 receptor suppresses lipopolysaccharide-induced TNF-α production through inhibition of PI 3-kinase/Akt and NF-kappaB activation in murine BV2 microglial cells. Neurosci Lett 2006; 396(1): 1-6.
[] [PMID: 16324785]
Choi IY, Lee JC, Ju C, et al. A3 adenosine receptor agonist reduces brain ischemic injury and inhibits inflammatory cell migration in rats. Am J Pathol 2011; 179(4): 2042-52.
[] [PMID: 21854743]
Canavan C, West J, Card T. Review article: The economic impact of the irritable bowel syndrome. Aliment Pharmacol Ther 2014; 40(9): 1023-34.
[] [PMID: 25199904]
Chang L, Lembo A, Sultan S. American Gastroenterological Association Institute Technical Review on the pharmacological management of irritable bowel syndrome. Gastroenterology 2014; 147(5): 1149-72.e2.
[] [PMID: 25224525]
Drossman DA. Functional gastrointestinal disorders: History, pathophysiology, clinical features, and Rome IV. Gastroenterology 2016; 150(6): 1262-79.
[] [PMID: 27144617]
Antonioli L, Fornai M, Colucci R, et al. Regulation of enteric functions by adenosine: Pathophysiological and pharmacological implications. Pharmacol Ther 2008; 120(3): 233-53.
[] [PMID: 18848843]
Kolachala VL, Obertone TS, Wang L, Merlin D, Sitaraman SV. Adenosine 2b receptor (A2bR) signals through adenylate cyclase (AC) 6 isoform in the intestinal epithelial cells. Biochim Biophys Acta 2006; 1760(7): 1102-8.
[] [PMID: 16631311]
Antonioli L, Fornai M, Awwad O, et al. Role of the A(2B) receptor-adenosine deaminase complex in colonic dysmotility associated with bowel inflammation in rats. Br J Pharmacol 2014; 171(5): 1314-29.
[] [PMID: 24286264]
Chassaing B, Aitken JD, Malleshappa M, Vijay-Kumar M. Dextran sulfate sodium (DSS)-induced colitis in mice. Curr Protoc Immunol 2014; 104(1): 25.
[PMID: 24510619]
Strohmeier GR, Reppert SM, Lencer WI, Madara JL. The A2b adenosine receptor mediates cAMP responses to adenosine receptor agonists in human intestinal epithelia. J Biol Chem 1995; 270(5): 2387-94.
[] [PMID: 7836474]
Crane JK, Olson RA, Jones HM, Duffey ME. Release of ATP during host cell killing by enteropathogenic E. coli and its role as a secretory mediator. Am J Physiol Gastrointest Liver Physiol 2002; 283(1): G74-86.
[] [PMID: 12065294]
Chandrasekharan BP, Kolachala VL, Dalmasso G, et al. Adenosine 2B receptors (A(2B)AR) on enteric neurons regulate murine distal colonic motility. FASEB J 2009; 23(8): 2727-34.
[] [PMID: 19357134]
Rybaczyk L, Wunderlich JE, Needleman B. Differential dysregulation of ADORA3, ADORA2A, ADORA2B, and P2RY14 expression profiles from 34 purine genes in mucosal biopsies and peripheral blood mononuclear cells in inflammatory bowel diseases. Gastroenterol 2007; 132: A-246.
Margo CE, Harman LE. Autoimmune disease: Conceptual history and contributions of ocular immunology. Surv Ophthalmol 2016; 61(5): 680-8.
[] [PMID: 27131478]
Liebman HA. Immune modulation for autoimmune disorders: Evolution of therapeutics. Semin Hematol 2016; 53(Suppl. 1): S23-6.
[] [PMID: 27312159]
Rodríguez D, Chakraborty S, Warnick E, et al. Structure-based screening of uncharted chemical space for atypical adenosine receptor agonists. ACS Chem Biol 2016; 11(10): 2763-72.
[] [PMID: 27439119]
Petrelli R, Scortichini M, Kachler S, et al. Exploring the role of N6-substituents in potent dual acting 5′-C-Ethyltetrazolyladenosine derivatives: Synthesis, binding, functional assays, and antinociceptive effects in mice. J Med Chem 2017; 60(10): 4327-41.
[] [PMID: 28447789]
Jones KR, Choi U, Gao J-L, et al. A novel method for screening adenosine receptor specific agonists for use in adenosine drug development. Sci Rep 2017; 7: 44816.
[] [PMID: 28317879]
Montesinos MC, Desai A, Delano D, et al. Adenosine A2A or A3 receptors are required for inhibition of inflammation by methotrexate and its analog MX-68. Arthritis Rheum 2003; 48(1): 240-7.
[] [PMID: 12528125]
Varani K, Vincenzi F, Tosi A, et al. Expression and functional role of adenosine receptors in regulating inflammatory responses in human synoviocytes. Br J Pharmacol 2010; 160(1): 101-15.
[] [PMID: 20331607]
Torres T, Filipe P. Small molecules in the treatment of psoriasis. Drug Dev Res 2015; 76(5): 215-27.
[] [PMID: 26255795]
Abdou AG, Hanout HM. Evaluation of survivin and NF-kappaB in psoriasis, an immunohistochemical study. J Cutan Pathol 2008; 35(5): 445-51.
[] [PMID: 18005174]
Nestle FO, Kaplan DH, Barker J. Psoriasis. N Engl J Med 2009; 361(5): 496-509.
[] [PMID: 19641206]
Burnstock G, Knight GE, Greig AV. Purinergic signaling in healthy and diseased skin. J Invest Dermatol 2012; 132: 526e46.
[] [PMID: 22158558]
Antonioli L, Csoka B, Fornai M, et al. Adenosine and inflammation: What’s new on the horizon? 2014.
Ernst PB, Garrison JC, Thompson LF. Much ado about adenosine: adenosine synthesis and function in regulatory T cell biology. J Immunol 2010; 185: 1993-8.
[] [PMID: 20686167]
Braun M, Lelieur K, Kietzmann M. Purinergic substances promote murine keratinocyte proliferation and enhance impaired wound healing in mice Wound Repair Regen 2006; 14: 152e61.
[] [PMID: 16630104]
Brown JR, Cornell K, Cook PW. Adenosine- and adeninenucleotidemediated inhibition of normal and transformed keratinocyte proliferation is dependent upon dipyridamole-sensitive adenosine transport. J Invest Dermatol 2000; 115: 849e59.
Andrés RM, Terencio MC, Arasa J, et al. Adenosine A2A and A2B receptors differentially modulate keratinocytes proliferation: Possible deregulation in psoriatic epidermis. J Invest Dermatol 2017; 137(1): 123-31.
[] [PMID: 27498346]
Ochaion A, Bar-Yehuda S, Cohen S, et al. The A3 adenosine receptor agonist CF502 inhibits the PI3K, PKB/Akt and NF-kappaB signaling pathway in synoviocytes from rheumatoid arthritis patients and in adjuvant-induced arthritis rats. Biochem Pharmacol 2008; 76(4): 482-94.
[] [PMID: 18602896]
Stamp LK, Hazlett J, Roberts RL, Frampton C, Highton J, Hessian PA. Adenosine receptor expression in rheumatoid synovium: A basis for methotrexate action. Arthritis Res Ther 2012; 14(3): R138.
[] [PMID: 22682496]
Ochaion A, Bar-Yehuda S, Cohen S, et al. The anti-inflammatory target A(3) adenosine receptor is over-expressed in rheumatoid arthritis, psoriasis and Crohn’s disease. Cell Immunol 2009; 258(2): 115-22.
[] [PMID: 19426966]
Madi L, Cohen S, Ochayin A, Bar-Yehuda S, Barer F, Fishman P. 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(1): 20-6.
[PMID: 17216675]
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(1): R33.
[] [PMID: 16507132]
El Maatougui A, Azuaje J, González-Gómez M, et al. Discovery of potent and highly selective A2B adenosine receptor antagonist chemotypes. J Med Chem 2016; 59(5): 1967-83.
[] [PMID: 26824742]
Carbajales C, Azuaje J, Oliveira A, et al. Enantiospecific Recognition at the A2B Adenosine Receptor by Alkyl 2-Cyanoimino-4-substituted-6-methyl-1,2,3,4-tetrahydropyrimidine-5-carboxylates. J Med Chem 2017; 60(8): 3372-82.
[] [PMID: 28368607]
Rodríguez D, Gao ZG, Moss SM, Jacobson KA, Carlsson J. Molecular docking screening using agonist-bound GPCR structures: Probing the A2A adenosine receptor. J Chem Inf Model 2015; 55(3): 550-63.
[] [PMID: 25625646]
Kolb P, Phan K, Gao ZG, Marko AC, Sali A, Jacobson KA. Limits of ligand selectivity from docking to models: In silico screening for A(1) adenosine receptor antagonists. PLoS One 2012; 7(11)e49910
[] [PMID: 23185482]
Deb PK, Mailavaram R, Chandrasekaran B, et al. Synthesis, adenosine receptor binding and molecular modelling studies of novel thieno[2,3-d]pyrimidine derivatives. Chem Biol Drug Des 2018; 91(4): 962-9.
[] [PMID: 29194979]
Cheng F, Xu Z, Liu G, Tang Y. Insights into binding modes of adenosine A(2B) antagonists with ligand-based and receptor-based methods. Eur J Med Chem 2010; 45(8): 3459-71.
[] [PMID: 20537438]
Song Y, Coupar IM, Iskander MN. Structural predictions of adenosine 2B antagonist affinity using molecular field analysis. QSAR 2001; 20(1): 23-30.
Pran Kishore D, Balakumar C, Raghuram Rao A, Roy PP, Roy K. QSAR of adenosine receptor antagonists: Exploring physicochemical requirements for binding of pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine derivatives with human adenosine A(3) receptor subtype. Bioorg Med Chem Lett 2011; 21(2): 818-23.
[] [PMID: 21163647]
Shaik K, Deb PK, Mailavaram RP, et al. 7-Amino-2-aryl/hetero-aryl-5-oxo-5,8-dihydro-[1,2,4]triazolo[1,5-a] pyridine- 6- carbonitriles: Synthesis and adenosine receptor binding studies. Chem Biol Drug Des 2019; 94(2): 1568-73.
[] [PMID: 30985956]
Al-Qattan MN. Mand Mordi. MN. Molecular basis of modulating adenosine receptors activities. Curr Pharm Des 2019; 25(7): 817-31.
[] [PMID: 30834826]
Agrawal N, Chandrasekaran B, Al-Aboudi A. Al-AboudiA. Recent advances in the in-silico structure-based and ligand-based approaches for the design and discovery of agonists and antagonists of A2A adenosine receptor. Curr Pharm Des 2019; 25(7): 774-82.
[] [PMID: 30848185]
Deb PK, Chandrasekaran B, Mailavaram R, Tekade RK, Jaber AMY. Molecular modeling approaches for the discovery of adenosine A2B receptor antagonists: Current status and future perspectives. Drug Discov Today 2019.
[] [PMID: 31103731]
Deb PK. Recent updates in the computer aided drug design strategies for the discovery of agonists and antagonists of adenosine receptors. Curr Pharm Des 2019; 25(7): 747-9.
Al-Shar’i NA, Al-Balas QA. Molecular dynamics simulations of adenosine receptors: Advances, applications and trends. Curr Pharm Des 2019; 25(7): 783-816.
[] [PMID: 30834825]

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