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A3 Adenosine Receptor in the Pulmonary System

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A3 Adenosine Receptors from Cell Biology to Pharmacology and Therapeutics

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Abstract

A3 adenosine receptor (A3AR) is highly expressed in the airways of both man and other species. Within the human lungs, A3AR appears mostly on circulating and resident inflammatory cells, particularly granular leukocytes such as eosinophils, neutrophils and monocytes. The human A3AR mediates anti-inflammatory cell responses upon its activation on these cells, via direct effect on cell migration, degranulation or the production of cytokines, however, stimulatory effects were also reported. In other species, high levels of A3AR expression were also found on lung mast cells.

The A3AR has emerged as an AR subtype that may serve important regulatory roles in the inflamed airways. A3AR transcript and protein levels are elevated in lung biopsies from patients with asthma and chronic obstructive pulmonary disease, suggesting increased signaling through this receptor. The importance of eosinophils in allergy and asthma is well recognized. Therefore, current investigations evaluate the beneficial effect of targeting A3AR for the treatment of eosinophil-dependent pulmonary diseases such as asthma, chronic obstructive pulmonary disease and rhinitis.

A3AR agonists also attenuate ischemia–reperfusion-induced lung injury in animal models, through the reduction of apoptosis, promotion of cell survival and anti-inflammatory effects. This protectivity is associated with a modified lobar arterial pressure which either evolves from the attenuated inflammation or results from a direct vascular impact of A3AR agonists. The role of A3AR in the pulmonary circulation remains to be elucidated. A3AR agonists were shown to exert species-dependent hemodynamic effects in the pulmonary system, mostly vasodilation. Still, thus far there is no data to demonstrate a direct effect of A3AR activation on the pulmonary vasculature, although an indirect effect was exhibited in rodents, through mast cell activation.

This chapter summarizes current experimental and human data on the roles of A3AR in the healthy, injured and hyperresponsive airways and lungs and suggests that A3AR may become a promising target to exploit in the development of innovative therapeutic strategies.

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References

  • Aarab L, Siaume-Perez S, Chabades D (1999) Cell-specific coupling of PGE2 to different transduction pathways in arginine vasopressinand glucagon-sensitive segments of the rat renal tubule. Br J Pharmacol 126(4):1041–1049

    Article  PubMed  CAS  Google Scholar 

  • Abbracchio MP, Ceruti S, Brambilla R, Franceschi C, Malorni W, Jacobson KA, von Lubitz DK, Cattabeni F (1997) Modulation of apoptosis by adenosine in the central nervous system: A possible role for the A3 receptor. Pathophysiological significance and therapeutic implications for neurodegenerative disorders. Ann N Y Acad Sci 825:11–22

    Article  PubMed  CAS  Google Scholar 

  • Abe J, Baines CP, Berk BC (2000) Role of mitogen-activated protein kinases in ischemia and reperfusion injury: the good and the bad. Circ Res 86(6):607–609

    PubMed  CAS  Google Scholar 

  • Abebe W, Mustafa SJ (1998) A1 adenosine receptor-mediated Ins(1,4,5)P3 generation in allergic rabbit airway smooth muscle. Am J Physiol 275(5 Pt 1):L990–L997

    PubMed  CAS  Google Scholar 

  • Abraham E (2003) Neutrophils and acute lung injury. Crit Care Med 31(4 Suppl):S195–S199

    Article  PubMed  Google Scholar 

  • Ali H, Cunha-Melo JR, Saul WF, Beaven MA (1990) Activation of phospholipase C via adenosine receptors provides synergistic signals for secretion in antigen-stimulated RBL-2H3 cells. Evidence for a novel adenosine receptor. J Biol Chem 265(2):745–753

    PubMed  CAS  Google Scholar 

  • Al-Mehdi AB, Fisher AB (1998) Invited editorial on “tumor necrosis factor-alpha in ischemia and reperfusion injury in rat lungs”. J Appl Physiol 85(6):2003–2004

    PubMed  CAS  Google Scholar 

  • Angle N, Hoyt DB, Cabello-Passini R, Herdon-Remelius C, Loomis W, Junger WG (1998) Hypertonic saline resuscitation reduces neutrophil margination by suppressing neutrophil L selectin expression. J Trauma 45(1):7–13

    Article  PubMed  CAS  Google Scholar 

  • Auchampach JA, Jin X, Wan TC, Caughey GH, Linden J (1997) Canine mast cell adenosine receptors: cloning and expression of the A3 receptor and evidence that degranulation is mediated by the A2B receptor. Mol Pharmacol 52(5):846–860

    PubMed  CAS  Google Scholar 

  • Aune TM, McGrath KM, Sarr T, Bombara P, Kelley KA (1993) Expression of 5HT1a receptors on activated human T cells. Regulation of cyclic AMP levels and T cell proliferation by 5-HT. J Immunol 151(3):1175–1183

    Google Scholar 

  • Bai TR, Weir T, Walker B, Salvatore CA, Johnson RG, Jacobson MA (1994) Localization of adenosine-A3 receptors by in-situ hybridization in human lung. FASEB J 8:A800

    Google Scholar 

  • Barnes PJ (1989) New concepts in the pathogenesis of bronchial hyperresponsiveness and asthma. J Allergy Clin Immunol 83(6):1013–1026

    Article  PubMed  CAS  Google Scholar 

  • Berne RM (1963) Cardiac nucleotides in hypoxia: possible role in regulation of coronary blood flow. Am J Physiol 204:317–322

    PubMed  CAS  Google Scholar 

  • Bjorck T, Gustafsson LE, Dahlen SE (1992) Isolated bronchi from asthmatics are hyperresponsive to adenosine, which apparently acts indirectly by liberation of leukotrienes and histamine. Am Rev Respir Dis 145(5):1087–1091

    PubMed  CAS  Google Scholar 

  • Bogoyevitch MA, Gillespie-Brown J, Ketterman AJ, Fuller SJ, Ben-Levy R, Ashworth A, Marshall CJ, Sugden PH (1996) Stimulation of the stress-activated mitogen-activated protein kinases and c-jun N-terminal kinases are activated by ischemia/reperfusion. Circ Res 79(2):162–173

    PubMed  CAS  Google Scholar 

  • Borghi-Scoazec G, Scoazec JY, Durand F, Bernuau J, Belghiti J, Feldmann G, Henin D, Degott C (1997) Apoptosis after ischemia-reperfusion in human liver allografts. Liver Transpl Surg 3(4):407–415

    Article  PubMed  CAS  Google Scholar 

  • Bouma MG, Stad RK, Van Den Wildenberg F, Buman WA (1994) Differential regulatory effects of adenosine on cytokine release by activated human monocytes. J Immunol 153(9):4159–4168

    PubMed  CAS  Google Scholar 

  • Bouma MG, Jeunhomme TM, Boyle DL, Dentener MA, Voitenok NN, van den Wildenberg FA, Buurman WA (1997) Adenosine inhibits neutrophil degranulation in activated human whole blood: involvement of adenosine A2 and A3 receptors. J Immunol 158(11):5400–5408

    PubMed  CAS  Google Scholar 

  • Bowlin TL, Borcherding DR, Edwards CK 3rd, McWhinney CD (1997) Adenosine A3 receptor agonists inhibit murine macrophage tumor necrosis factor-alpha production in vitro and in vivo. Cell Mol Biol 43(3):345–349

    PubMed  CAS  Google Scholar 

  • Broussas M, Cornillet-Lefebvre P, Potron G, Nguyen P (1999) Inhibition of fMLP-triggered respiratory burst of human monocytes by adenosine: involvement of A3 adenosine receptor. J Leukoc Biol 66(3):495–501

    PubMed  CAS  Google Scholar 

  • Brown RA, Clarke GW, Ledbetter CL, Hurle MJ, Denyer JC, Simcock DE, Coote JE, Savage TJ, Murdoch RD, Page CP, Spina D, OConnor BJ (2008a) Elevated expression of adenosine A1 receptor in bronchial biopsy specimens from asthmatic subjects. Eur Respir J 31(2):311–319

    Google Scholar 

  • Brown RA, Spina D, Page CP (2008b) Adenosine receptors and asthma. Br J Pharmacol 153(Suppl 1):S446–S456

    PubMed  CAS  Google Scholar 

  • Bulanova E, Budagian V, Orinska Z, Hein M, Petersen F, Thon L, Adam D, Bulfone-Paus S (2005) Extracellular ATP induces cytokine expression and apoptosis through P2X7 receptor in murine mast cells. J Immunol 174(7):3880–3890

    PubMed  CAS  Google Scholar 

  • Burns AT, Davies DR, McLaren AJ, Cerundolo L, Morris PJ, Fuggle SV (1998) Apoptosis in ischemia/reperfusion injury of human renal allografts. Transplantation 66(7):872–876

    Article  PubMed  CAS  Google Scholar 

  • Carruthers AM, Fozard JR (1993a) Adenosine A3 receptors mediate hypotension in the angiotensin II-supported circulation of the pithed rat. Br J Pharmacol 109(1):3–5

    PubMed  Google Scholar 

  • Carruthers AM, Fozard JR (1993b) Effect of pertussis toxin treatment on the putative adenosine A3 receptor-mediated hypotensive response in the rat. Eur J Pharmacol 250(1):185–188

    Article  PubMed  CAS  Google Scholar 

  • Caruso M, Holgate ST, Polosa R (2006) Adenosine signalling in airways. Curr Opin Pharmacol 6(3):251–256

    Article  PubMed  CAS  Google Scholar 

  • Chan TO, Rittenhouse SE, Tsichlis PN (1999) AKT/PKB and other D3 phosphoinositide-regulated kinases: kinase activation by phosphoinositide-dependent phosphorylation. Annu Rev Biochem 68:965–1014

    Article  PubMed  CAS  Google Scholar 

  • Chang L, Karin M (2001) Mammalian MAP kinase signalling cascades. Nature 410(6824):37–40

    Article  PubMed  CAS  Google Scholar 

  • Chen Y, Hashiguchi N, Yip L, Junger WG (2006) Hypertonic saline enhances neutrophil elastase release through activation of P2 and A3 receptors. Am J Physiol Cell Physiol 290(4):C1051–C1059

    Article  PubMed  CAS  Google Scholar 

  • Cheng DY, DeWitt BJ, Suzuki F, Neely CF, Kadowitz PJ (1996) Adenosine A1 and A2 receptors mediate tone-dependent responses in feline pulmonary vascular bed. Am J Physiol 270(1 Pt 2):H200–H207

    PubMed  CAS  Google Scholar 

  • Clarke H, Cushley MJ, Persson CG, Holgate ST (1989) The protective effects of intravenous theophylline and enprofylline against histamine- and adenosine 50-monophosphate-provoked bronchoconstriction: implications for the mechanisms of action of xanthine derivatives in asthma. Pulm Pharmacol 2(3):147–154

    Article  PubMed  CAS  Google Scholar 

  • Collis MG, Hourani SM (1993) Adenosine receptor subtypes. Trends Pharmacol Sci 14(10):360–366

    Article  PubMed  CAS  Google Scholar 

  • Cooper DMF, Mons N, Karpen JW (1995) Adenylyl cyclases and the interaction between calcium and cAMP signaling. Nature 374(6521):421–424

    Article  PubMed  CAS  Google Scholar 

  • Cowen DS, Molinoff PB, Manning DR (1997) 5HT1A receptor mediated increases in receptor expression and activation of nuclear factor-κB in transfected Chinese hamster ovarycells. Mol Pharmacol 52(2):221–226

    PubMed  CAS  Google Scholar 

  • Cronstein BN, Daguma L, Nichols D, Hutchison AJ, Williams M (1990) The adenosine/neutrophil paradox resolved: human neutrophils possess both A1 and A2 receptors that promote chemotaxis and inhibit O2 generation, respectively. J Clin Invest 85(4):1150–1157

    Article  PubMed  CAS  Google Scholar 

  • Cronstein BN, Levin RI, Philips M, Hirschhorn R, Abramson SB, Weissmann G (1992) Neutrophil adherence to endothelium is enhanced via adenosine A1 receptors and inhibited via adenosine A2 receptors. J Immunol 148(7):2201–2206

    PubMed  CAS  Google Scholar 

  • Cushley MJ, Tattersfield AE, Holgate ST (1984) Adenosine-induced bronchoconstriction in asthma. Antagonism by inhaled theophylline. Am Rev Respir Dis 129(3):380–384

    PubMed  CAS  Google Scholar 

  • De Perrot M, Liu M, Waddell TK, Keshavjee S (2003) Ischemia-reperfusion induced lung injury. Am J Respir Crit Care Med 167(4):490–511

    Article  PubMed  Google Scholar 

  • Di Virgilio F, Chiozzi P, Ferrari D, Falzoni S, Sanz JM, Morelli A, Torboli M, Bolognesi G, Baricordi OR (2001) Nucleotide receptors: an emerging family of regulatory molecules in blood cells. Blood 97(3):587–600

    Article  PubMed  Google Scholar 

  • Dixon AK, Gubitz AK, Sirinathsinghji DJ, Richardson PJ, Freeman TC (1996) Tissue distribution of adenosine receptor mRNAs in the rat. Br J Pharmacol 118(6):1461–1468

    PubMed  CAS  Google Scholar 

  • Douillet CD, Robinson WP 3rd, Zarzaur BL, Lazarowski ER, Boucher RC, Rich PB (2005) Mechanical ventilation alters airway nucleotides and purinoceptors in lung and extrapulmonary organs. Am J Respir Cell Mol Biol 32(1):52–58

    Article  PubMed  CAS  Google Scholar 

  • Douillet CD, Robinson WP 3rd, Milano PM, Boucher RC, Rich PB (2006) Nucleotides induce IL-6 release from human airway epithelia via P2Y2. p38 MAPK-dependent pathways. Am J Physiol Lung Cell Mol Physiol 291(4):L734–L746

    Google Scholar 

  • Doyle MP, Linden J, Duling BR (1994) Nucleoside induced arteriolar constriction: a mast cell dependent response. Am J Physiol 266(5 Pt 2):H2042–H2050

    PubMed  CAS  Google Scholar 

  • Drake I, Routledge PA, Richards R (1994) Bronchospasm induced by intravenous adenosine. Hum Exp Toxicol 13(4):263–265

    Article  PubMed  CAS  Google Scholar 

  • Durand IH, Green RD (2001) Cloning of a chick A3 adenosine receptor: characterization of ligand binding and receptor-effector coupling of chick A1 and A3 adenosine receptors. Naunyn Schmiedebergs Arch Pharmacol 363(1):81–89

    Article  PubMed  CAS  Google Scholar 

  • Durham RM, Moran JJ, Mazuski JE, Shapiro MJ, Baue AE, Flint LM (2003) Multiple organ failure in trauma patients. J Trauma 55(4):608–616

    Article  PubMed  Google Scholar 

  • Eckle T, Grenz A, Laucher S, Eltzschig HK (2008) A2B adenosine receptor signaling attenuates acute lung injury by enhancing alveolar fluid clearance in mice. J Clin Invest 118(10):3301–3315

    PubMed  CAS  Google Scholar 

  • El-Kashef H, Elmazar MM, Al-Shabanah OA, Al-Bekairi AM (1999) Effect of adenosine on pulmonary circulation of rabbits. Gen Pharmacol 32(3):307–313

    Article  PubMed  CAS  Google Scholar 

  • Englert M, Quitterer U, Klotz KN (2002) Effector coupling of stably transfected human A3 adenosine receptors in CHO cells. Biochem Pharmacol 64(1):61–65

    Article  PubMed  CAS  Google Scholar 

  • Eppinger MJ, Jones ML, Deeb GM, Bolling SF, Ward PA (1995) Pattern of injury and the role of neutrophils in reperfusion injury of rat lung. J Surg Res 58(6):713–718

    Article  PubMed  CAS  Google Scholar 

  • Eppinger MJ, Deeb GM, Bolling SF, Ward PA (1997) Mediators of ischemia–reperfusion injury of rat lung. Am J Pathol 150(5):1773–1784

    PubMed  CAS  Google Scholar 

  • Erdogan M, Kalaycioglu S, Iriz E (2005) Protective effect of aprotinin against lung damage in patients undergoing CABG surgery. Acta Cardiol 60(4):367–372

    Article  PubMed  Google Scholar 

  • Ezeamuzie CI (2001) Involvement of A3 receptors in the potentiation byadenosine of the inhibitory effect of theophylline on human eosinophil degranulation: possible novel mechanism of the anti-inflammatory action of theophylline. Biochem Pharmacol 61(12):1551–1559

    Article  PubMed  CAS  Google Scholar 

  • Ezeamuzie CI, Philips E (1999) Adenosine A3 receptors on human eosinophils mediate inhibition of degranulation and superoxide anion release. Br J Pharmacol 127(1):188–194

    Article  PubMed  CAS  Google Scholar 

  • Ezeamuzie CI, Philips E (2003) Positive coupling of atypical adenosine A3 receptors on human eosinophils to adenylyl cyclase. Biochem Biophys Res Commun 300(3):712–718

    Article  PubMed  CAS  Google Scholar 

  • Fan M, Qin W, Mustafa SJ (2003) Characterization of adenosine receptor(s) involved in adenosine-induced bronchoconstriction in an allergic mouse model. Am J Physiol Lung Cell Mol Physiol 284(6):L1012–L1019

    PubMed  CAS  Google Scholar 

  • Feoktistov I, Biaggioni I (1998) Pharmacological characterization of adenosine A2B receptors: studies in human mast cells coexpressing A2A and A2B adenosine receptor subtypes. Biochem Pharmacol 55(5):627–633

    Article  PubMed  CAS  Google Scholar 

  • Feoktistov I, Polosa R, Holagate ST, Biaggioni I (1998) Adenosine A2B receptors: a novel therapeutic target in asthma? Trends Pharmacol Sci 19(4):148–153

    Article  PubMed  CAS  Google Scholar 

  • Fischer S, Cassivi SD, Xavier A, Cardella JA, Cutz E, Edwards V, Liu M, Keshavjee S (2000a) Cell death in human lung transplantation: apoptosis induction in human lungs during ischemia and after transplantation. Ann Surg 231(3):424–431

    Article  PubMed  CAS  Google Scholar 

  • Fischer S, MacLean AA, Liu M, Cardella JA, Slutsky AS, Suga M, Moreira JF, Keshavjee S (2000b) Dynamic changes and necrotic cell death correlate with severity of ischemia-reperfusion injury in lung transplantation. Am J Respir Crit Care Med 162(5):1932–1939

    PubMed  CAS  Google Scholar 

  • Fiser SM, Tribble CG, Long SM, Kaza AK, Cope JT, Laubach VE, Kern JA, Kron IL (2001) Lung transplant reperfusion injury involves pulmonary macrophages and circulating leukocytes in a biphasic response. J Thorac Cardiovasc Surg 121(6):1069–1075

    Article  PubMed  CAS  Google Scholar 

  • Fiser SM, Tribble CG, Kaza AK, Long SM, Kern JA, Cassada DC, Linden J, Rieger J, Laubach VE, Matisoff A, Kron IL (2002) Adenosine A2A receptor activation decreases reperfusion injury associated with high-flow reperfusion. J Thorac Cardiovasc Surg 124(5):973–978

    Article  PubMed  CAS  Google Scholar 

  • Fishman P, Madi L, Bar-Yehuda S, Barer F, Del Valle L, Khalili K (2002) Evidence for involvement of Wnt signaling pathway in IB-MECA mediated suppression of melanoma cells. Oncogene 21(25):4060–4064

    Article  PubMed  CAS  Google Scholar 

  • Fozard JR, Pfannkuche HJ, Schuurman HJ (1996) Mast cell degranulation following adenosine A3 receptor activation in rats. Eur J Pharmacol 298(3):293–297

    Article  PubMed  CAS  Google Scholar 

  • Freude B, Masters TN, Robicsek F, Fokin A, Kostin S, Zimmermann R, Ullmann C, Lorenz-Meyer S, Schaper J (2000) Apoptosis is initiated by myocardial ischemia and executed during reperfusion. J Mol Cell Cardiol 32(2):197–208

    Article  PubMed  CAS  Google Scholar 

  • Frigas E, Gleich GJ (1986) The eosinophil and the pathophysiology of asthma. J Allergy Clin Immunol 77(4):527–537

    Article  PubMed  CAS  Google Scholar 

  • Fullerton DA, Kirson LE, Jones SD, McIntyre RC (1996) Adenosine is a selective pulmonary vasodilator in cardiac surgical patients. Chest 109(1):41–46

    Article  PubMed  CAS  Google Scholar 

  • Gao Z, Li BS, Day YJ, Linden J (2001) A3 adenosine receptor activation triggers phosphorylation of protein kinase B and protects rat basophilic leukemia 2H3 mast cells from apoptosis. Mol Pharmacol 59(1):76–82

    PubMed  CAS  Google Scholar 

  • Gessi S, Varani K, Merighi S, Morelli A, Ferrari D, Leung E, Baraldi LG, Spalluto G, Borea PA (2001) Pharmacological and biochemical characterization of A3 adenosine receptors in Jurkat T cells. Br J Pharmacol 134(1):116–126

    Article  PubMed  CAS  Google Scholar 

  • Gessi S, Varani K, Merighi S, Cattabriga E, Iannotta V, Leung E, Baraldi PG, Borea PA (2002) A3 adenosine receptors in human neutrophils and promyelocytic HL60 cells: a pharmacological and biochemical study. Mol Pharmacol 61(2):15–24

    Article  Google Scholar 

  • Gietzen K (1983) Comparison of the calmodulin antagonists compound 48/80 and calmidazolium. Biochem J 216(3):611–616

    PubMed  CAS  Google Scholar 

  • Gietzen K, Adamczyk-Engelmann P, Wüthrich A, Konstantinova A, Bader H (1983) Compound 48/80 is a selective and powerful inhibitor of calmodulin-regulated functions. Biochim Biophys Acta 736(1):109–118

    Article  PubMed  CAS  Google Scholar 

  • Gleich G (1990) The eosinophil and bronchial asthma. Current understanding. J Allergy Clin Immunol 85(2):422–426

    Article  PubMed  CAS  Google Scholar 

  • Guo Y, Bolli R, Bao W, Wu WJ, Black RG Jr, Murphree SS, Salvatore CA, Jacobson MA, Auchampach JA (2001) Targeted deletion of the A3 adenosine receptor confers resistance to myocardial ischemic injury and does not prevent early preconditioning. J Mol Cell Cardiol 33(4):825–830

    Article  PubMed  CAS  Google Scholar 

  • Hannon JP, Pfannkuche HJ, Fozard JR (1995) A role for mast cells in adenosine A3 receptor-mediated hypotension in the rat. Br J Pharmacol 115(6):945–952

    PubMed  CAS  Google Scholar 

  • Hashiguchi N, Lum L, Romeril E, Chen Y, Yip L, Hoyt DB, Junger WG (2007) Hypertonic saline resuscitation: efficacy may require early treatment in severely injured patients. J Trauma 62(2):299–306

    Article  PubMed  Google Scholar 

  • Haskó G, Szabó C, Németh ZH, Kvetan V, Pastores SM, Vizi ES (1996) Adenosine receptor agonists differentially regulate IL-10, TNF-alpha, and nitric oxide production in RAW 264.7 macrophages and in endotoxemic mice. J Immunol 157(10):4634–4640

    Google Scholar 

  • Haskó G, Nemeth ZH, Vizi ES, Salzman AL, Szabo C (1998) An agonist of adenosine A3 receptors decreases interleukin-12 and interferon-gamma production and prevents lethality in endotoxemic mice. Eur J Pharmacol 358(3):261–268

    Article  PubMed  Google Scholar 

  • Haynes J Jr, Obiako B, Thompson WJ, Downey J (1995) Adenosine-induced vasodilation: receptor characterization in pulmonary circulation. Am J Physiol 268(5):H1862–H1868

    Google Scholar 

  • Haynes J Jr, Obiako B, Babal P, Stevens T (1999) 5-(N-ethylcarboxamido) adenosine desensitizes the A2b-adenosine receptor in lung circulation. Am J Physiol 276(6 Pt 2):H1877–H1883

    Google Scholar 

  • Hill RJ, Oleynek JJ, Hoth CF, Ravi Kiron MA, Weng W, Webster RT, Tracey WR, Knight DR, Buchholz RA, Kennedy SP (1997) Cloning, expression and pharmacological characterization of rabbit adenosine A1 and A3 receptors. J Pharmacol Exp Ther 280(1):122–128

    PubMed  CAS  Google Scholar 

  • Hill RJ, Oleynek JJ, Magee W, Knight DR, Tracey WR (1998) Relative importance of adenosine A1 and A3 receptors in mediating physiological or pharmacological protection from ischemic myocardial injury in the rabbit heart. J Mol Cell Cardiol 30(3):579–585

    Article  PubMed  CAS  Google Scholar 

  • Hoffman HM, Walker LL, Marquardt DL (1997) Mast cell adenosine induced calcium mobilization via Gi3 and Gq proteins. Inflammation 21(1):55–68

    Article  PubMed  CAS  Google Scholar 

  • Holgate ST (2005) The identification of the adenosine A2B receptor as a novel therapeutic target in asthma. Br J Pharmacol 145(8):1009–1015

    Article  PubMed  CAS  Google Scholar 

  • Hua X, Chason KD, Fredholm BB, Deshpande DA, Penn RB, Tilley SL (2008) Adenosine induces airway hyperresponsiveness through activation of A3 receptors on mast cells. J Allergy Clin Immunol 122(1):107–113

    Article  PubMed  CAS  Google Scholar 

  • Huszar E, Vass G, Vizi E, Csoma Z, Barát E, Molnár Világos G, Herjavecz I, Horváth I (2002) Adenosine in exhaled breath condensate in healthy volunteers and in patients with asthma. Eur Respir J 20(6):1393–1398

    Article  PubMed  CAS  Google Scholar 

  • Ikeda H, Suzuki Y, Suzuki M, Koike M, Tamura J, Tong J, Nomura M, Itoh G (1998) Apoptosis is a major mode of cell death caused by ischaemia and ischaemia/reperfusion injury to the rat intestinal epithelium. Gut 42(4):530–537

    Article  PubMed  CAS  Google Scholar 

  • Inoue Y, Seiyama A, Tanaka H, Isao U, Akimau P, Nishino M, Shimazu T, Sugimoto H (2005) Protective effects of a selective neutrophil elastase inhibitor (sivelestat) on LSP-induced acute dysfunction of the pulmonary microcirculation. Crit Care Med 33(8):1814–1822

    Article  PubMed  CAS  Google Scholar 

  • Inoue Y, Tanaka H, Ogura H, Ukai I, Fujita K, Hosotsubo H, Shimazu T, Sugimoto H (2006) A neutrophil elastase inhibitor, sivelestat, improves leukocyte deformability in patients with acute lung injury. J Trauma 60(5):936–943

    Article  PubMed  CAS  Google Scholar 

  • Jackson KA (1998) Adenosine A3 receptors: novel ligands and paradoxical effects. Trends Pharmacol Sci 19(5):184–191

    Article  Google Scholar 

  • Jacobson KA (1998) Adenosine A3 receptors: novel ligands and paradoxical effects. Trends Pharmacol Sci 19(5):184–91

    Google Scholar 

  • Jacobson KA, Hoffmann C, Cattabeni F, Abbracchio MP (1999) Adenosine-induced cell death: evidence for receptor-mediated signaling. Apoptosis 4(3):197–211

    Article  PubMed  CAS  Google Scholar 

  • Jatakanon A, Uasuf C, Maziak W, Lim S, Chung KF, Barnes PJ (1999) Neutrophilic inflammation in severe persistent asthma. Am J Respir Crit Care Med 160(5 Pt 1):1532–1539

    PubMed  CAS  Google Scholar 

  • Jiang XW, Kambara K, Gotoh N, Nishgaki K, Fujiwara H (1998) Effect of low-dose beraprost sodium, a stable prostaglandin I2 analogue, on reperfusion injury to rabbit lungs. Am J Respir Crit Care Med 158(5 Pt 1):1669–1675

    PubMed  CAS  Google Scholar 

  • Jin X, Shepherd RK, Duling BR, Linden J (1997) Inosine binds to A3 adenosine receptors and stimulates mast cell degranulation. J Clin Invest 100(11):2849–2857

    Article  PubMed  CAS  Google Scholar 

  • Joad JP (1990) Characterization of the human peripheral lung adenosine receptor. Am J Respir Cell Mol Biol 2(2):193–198

    PubMed  CAS  Google Scholar 

  • Jordan JE, Thourani VH, Auchampach JA, Robinson JA, Wang NP, Vinten-Johansen J (1999) A3 adenosine receptor activation attenuates neutrophil function and neutrophil-mediated reperfusion injury. Am J Physiol – Heart Circ Physiol 277(5):H1895–H1905

    Google Scholar 

  • Jordan S, Mitchell JA, Quinlan GJ, Goldstraw P, Evans TW (2000) The pathogenesis of lung injury following pulmonary resection. Eur Respir J 15(4):790–799

    Article  PubMed  CAS  Google Scholar 

  • Junger WG, Liu FC, Loomis WH, Hoyt DB, Junger WG, Liu FC, Loomis WH et al (1994) Hypertonic saline enhances cellular immune function. Circ Shock 42(4):190–196

    PubMed  CAS  Google Scholar 

  • Kawashima Y, Takeyoshi I, Otani Y, Koibuchi Y, Yoshinari D, Koyama T, Kobayashi M, Matsumoto K, Morishita Y (2001) FR167653 attenuates ischemia and reperfusion injury of the rat lung with suppressing p38 mitogen-activated protein kinase. J Heart Lung Transplant 20(5):568–574

    Article  PubMed  CAS  Google Scholar 

  • Khan TA, Bianchi C, Ruel M, Voisine P, Sellke FW (2004) Mitogen-activated protein kinase pathways and cardiac surgery. J Thorac Cardiovasc Surg 127(3):806–811

    Article  PubMed  CAS  Google Scholar 

  • Khimenko PL, Moore TM, Hill LW, Wilson PS, Coleman S, Rizzo A, Taylor AE (1995) Adenosine A2 receptors reverse ischemia-reperfusion lung injury independent of β-receptors. J Appl Physiol 78(3):990–996

    PubMed  CAS  Google Scholar 

  • King RC, Binns OA, Rodriguez F, Kanithanon RC, Daniel TM, Spotnitz WD, Tribble CG, Kron IL (2000) Reperfusion injury significantly impacts clinical outcome after pulmonary transplantation. Ann Thorac Surg 69(6):1681–1685

    Article  PubMed  CAS  Google Scholar 

  • Kita H, Abu-Ghazaleh RI, Gleich GJ, Abraham RT (1991) Regulation of Ig-induced eosinophil degranulation byadenosine 30, 50-cyclic monophosphate. J Immunol 146(8):2712–2718

    PubMed  CAS  Google Scholar 

  • Knight D, Zheng X, Rocchini C, Jacobson M, Bai T, Walker B (1997) Adenosine A3 receptor stimulation inhibits migration of human eosinophils. J Leukoc Biol 62(4):465–468

    PubMed  CAS  Google Scholar 

  • Kohno Y, Ji X, Mawhorter SD, Koshiba M, Jacobson KA (1996) Activation of A3 adenosine receptors on human eosinophils elevates intracellular calcium. Blood 88(9):3569–3574

    PubMed  CAS  Google Scholar 

  • Krasilnikov MA (2000) Phosphatidylinositol-3 kinase dependent pathways: the role in control of cell growth, survival, and malignant transformation. Biochemistry 65(1):59–67

    PubMed  CAS  Google Scholar 

  • Krishnadasan B, Naidu BV, Byrne K, Fraga C, Verrier ED, Mulligan MS (2003) The role of proinflammatory cytokines in lung ischemia-reperfusion injury. J Thorac Cardiovasc Surg 125(2):261–272

    Article  PubMed  CAS  Google Scholar 

  • Lai EW, Toledo-Pereyra LH, Walsh J, Lopez-Neblina F, Anaya-Prado R (2004) The role of MAP kinases in trauma and ischemiareperfusion. J Invest Surg 17(1):45–53

    PubMed  Google Scholar 

  • Lasley RD, Narayan P, Jahania MS, Partin EL, Kraft KR, Mentzer RM Jr (1999) Species-dependent hemodynamic effects of adenosine A3-receptor agonists IB-MECA and Cl-IB-MECA. Am J Physiol 276(2):H2076–H2084

    PubMed  CAS  Google Scholar 

  • Le Vraux V, Chen YL, Masson I, De Sousa M, Giroud JP, Florentin I, Chauvelot-Moachon L (1993) Inhibition of human monocyte TNF production by adenosine receptor agonists. Life Sci 52(24):1917–1924

    Article  PubMed  Google Scholar 

  • Lee JC, Laydon JT, McDonnell PC, Kumar S, Green D, McNulty D, Blumenthal MJ, Heys JR, Landvatter SW (1994) A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature 372(6508):739–746

    Article  PubMed  CAS  Google Scholar 

  • Linden J (1994) Cloned adenosine A3 receptors: pharmacological properties, species differences and receptor functions. Trends Pharmacol Sci 15(8):298–306

    Article  PubMed  CAS  Google Scholar 

  • Linden J (2001) Molecular approach to adenosine receptors: receptor-mediated mechanisms of tissue protection. Annu Rev Pharmacol Toxicol 41:775–787

    Article  PubMed  CAS  Google Scholar 

  • Linden J, Taylor HE, Robeva AS, Tucker AL, Stehle JH, Rivkees SA, Fink SJ, Reppert SM (1993) Molecular cloning and functional expression of a sheep A3 adenosine receptor with widespread tissue distribution. Mol Pharmacol 44(3):524–532

    PubMed  CAS  Google Scholar 

  • Ludviksdottir D, Janson C, Bjornsson E, Stalenheim G, Boman G, Hedenstrom H, Venge P, Gudbjornsson B, Valtysdottir S (2000) Different airway responsiveness profiles in atopic asthma, nonatopic asthma, and Sjogrens syndrome. BHR Study Group. Bronchial hyperresponsiveness. Allergy 55(3):259–265

    Article  PubMed  CAS  Google Scholar 

  • Marts BC, Baudendistel LJ, Naunheim KS, Dahms TE (1993) Protective effect of 2-chloroadenosine on lung ischemia reperfusion injury. J Surg Res 54(6):523–529

    Article  PubMed  CAS  Google Scholar 

  • Matot I, Jurim O (2001) Protective effect of acadesine on ischemia-reperfusion lung injury. Anesth Analg 92(3):590–595

    Article  PubMed  CAS  Google Scholar 

  • Matot I, Weiniger CF, Zeira E, Galun E, Joshi BV, Jacobson KA (2006) A3 adenosine receptors and mitogen-activated protein kinases in lung injury following in vivo reperfusion. Crit Care 10(2):R65

    Article  PubMed  Google Scholar 

  • Matot I, Einav S, Weiniger CF, Pearl RG, Abramovitch R, Joshi BV, Jacobson KA (2008) Lung injury after in vivo reperfusion: outcome at 27 hours after reperfusion. Anesthesiology 109(2):269–278

    Article  PubMed  Google Scholar 

  • Maxey TS, Enelow RI, Gaston B, Kron IL, Laubach VE, Doctor A (2004) Tumor necrosis factor-alpha from resident lung cells is a key initiating factor in pulmonary ischemia-reperfusion injury. J Thorac Cardiovasc Surg 127(2):541–547

    Article  PubMed  CAS  Google Scholar 

  • Mayer AM, Pittner RA, Lipscomb GE, Spitzer JA (1993) Effect of in vivo TNF administration on superoxide production and PKC activity of rat alveolar macrophages. Am J Physiol Lung Cell Mol Physiol 264(1 Pt 1):L43–L52

    CAS  Google Scholar 

  • McCallion K, Harkin DW, Gardiner KR (2004) Role of adenosine in immunomodulation: review of the literature. Crit Care Med 32(1):273–277

    Article  PubMed  CAS  Google Scholar 

  • McCormack DG, Clarke B, Barnes PJ (1989) Characterization of adenosine receptors in human pulmonary arteries. Am J Physiol 256(2):H41–H46

    PubMed  CAS  Google Scholar 

  • McWhinney CD, Dudley MW, Bowlin TL, Peet NP, Schook L, Bradshaw M, De M, Borcherding DR, Edwards CK 3rd (1996) Activation of adenosine A3 receptors on macrophages inhibits tumor necrosis factor-alpha. Eur J Pharmacol 310(2–3):209–216

    Article  PubMed  CAS  Google Scholar 

  • Mentzer RM Jr, Rubio R, Berne RM (1975) Release of adenosine by hypoxic canine lung tissue and its possible role in pulmonary circulation. Am J Physiol 229(6):1625–1631

    PubMed  CAS  Google Scholar 

  • Meyerhof W, Müller-Brechlin R, Richter D (1991) Molecular cloning of a novel putative G-protein coupled receptor expressed during rat spermiogenesis. FEBS Lett 284(2):155–160

    Article  PubMed  CAS  Google Scholar 

  • Milano PM, Douillet CD, Riesenman PJ, Robinson WP 3rd, Beidler SK, Zarzaur BL, Rich PB (2007) Intestinal ischemia-reperfusion injury alters purinergic receptor expression in clinically relevant extraintestinal organs. J Surg Res 145(2):272–278

    Article  PubMed  CAS  Google Scholar 

  • Murao Y, Hoyt DB, Loomis W, Namiki S, Patel N, Wolf P, Junger WG (2000) Does the timing of hypertonic saline resuscitation affect its potential to prevent lung damage? Shock 14(1):18–23

    Article  PubMed  CAS  Google Scholar 

  • Murao Y, Loomis W, Wolf P, Hoyt DB, Junger WG (2003) Effect of dose of hypertonic saline on its potential to prevent lung tissue damage in a mouse model of hemorrhagic shock. Shock 20(1):29–34

    Article  PubMed  Google Scholar 

  • Naidu BV, Krishnadasan B, Farivar AS, Woolley SM, Thomas R, Van Rooijen N, Verrier ED, Mulligan MS (2003) Early activation of the alveolar macrophage is critical to the development of lung ischemia-reperfusion injury. J Thorac Cardiovasc Surg 126(1):200–207

    Article  PubMed  CAS  Google Scholar 

  • Neely CF, Keith IM (1995) A1 adenosine receptor antagonists block ischemia reperfusion injury of the lung. Am J Physiol 268(6 Pt 1):L1036–L1046

    PubMed  CAS  Google Scholar 

  • Neely CF, Matot I (1996) Pharmacological probes for A1 and A2 adenosine receptors in vivo in feline pulmonary vascular bed. Am J Physiol 270(2 Pt 2):H610–H619

    PubMed  CAS  Google Scholar 

  • Neely CF, Kadowitz PJ, Lippton H et al (1989) Adenosine does not mediate the pulmonary vasodilator response of adenosine 5-triphosphate in the feline pulmonary vascular bed. J Pharmacol Exp Ther 250(1):170–176

    PubMed  CAS  Google Scholar 

  • Neumann J, Vahlensieck U, Boknik P, Linck B, Luss H, Muller FU, Matherne G, Schmitz W (1999) Functional studies in atrium overexpressing A1-adenosine receptors. Br J Pharmacol 128(7):1623–1629

    Article  PubMed  CAS  Google Scholar 

  • Ng CS, Wan S, Yim AP, Taylor R, Swetland JF (2002) Pulmonary dysfunction after cardiac surgery. Chest 121(4):1269–1277

    Article  PubMed  Google Scholar 

  • Nyce JW, Metzger WJ (1997) DNA antisense therapy for asthma in an animal model. Nature 385(6618):721–725

    Article  PubMed  CAS  Google Scholar 

  • Oosterhoff Y, de Jong JW, Jansen MA, Koeter GH, Postma DS (1993) Airway responsiveness to adenosine 5′-monophosphate in chronic obstructive pulmonary disease is determined by smoking. Am Rev Respir Dis 147(3):553–558

    PubMed  CAS  Google Scholar 

  • Phillis JW, Walter GA, ORegan MH, Stair RE (1987) Increases in cerebral cortical perfusate adenosine and inosine concentrations during hypoxia and ischemia. J Cereb Blood Flow Metab 7(6):679–686

    PubMed  CAS  Google Scholar 

  • Polosa R (2002) Adenosine-receptor subtypes: their relevance to adenosine-mediated responses in asthma and chronic obstructive pulmonary disease. Eur Respir J 20(2):488–496

    Article  PubMed  CAS  Google Scholar 

  • Polosa R, Ng WH, Crimi N, Vancheri C, Holgate ST, Church MK, Mistretta A (1995) Release of mast-cell-derived mediators after endobronchial adenosine challenge in asthma. Am J Respir Crit Care Med 151(3 Pt 1):624–629

    PubMed  CAS  Google Scholar 

  • Polosa R, Pagano C, Prosperini G, Low JL, Dokic D, Church MK-, Crimi N (1999) Histamine release upon adenosine 5′-monophosphate (AMP) nasal provocation in allergic subjects. Thorax 54(3):230–233

    Google Scholar 

  • Polosa R, Ciamarra I, Mangano G, Prosperini G, Pistorio MP, Vancheri C, Crimi N (2000) Bronchial hyperresponsiveness and airway inflammation markers in nonasthmatics with allergic rhinitis. Eur Respir J 15(1):30–35

    Article  PubMed  CAS  Google Scholar 

  • Polosa R, Rorke S, Holgate ST (2002) Evolving concepts on the value of adenosine hyperresponsiveness in asthma and chronic obstructive pulmonary disease. Thorax 57(7):649–654

    Article  PubMed  CAS  Google Scholar 

  • Porhanov VA, Poliakov IS, Selvaschuk AP, Grechishkin AI, Sitnik SD, Nikolaev IF, Efimtsev JP, Marchenko LG (2002) Indications and results of sleeve carinal resection. Eur J Cardiothorac Surg 22(5):685–694

    Article  PubMed  Google Scholar 

  • Ramkumar V, Stiles GL, Beaven MA, Ali H (1993) The A3 adenosine receptor is the unique adenosine receptor which facilitates release of allergic mediators in mast cells. J Biol Chem 268(23):16887–16890

    PubMed  CAS  Google Scholar 

  • Rangel-Frausto MS, Pittet D, Costigan M, Hwang T, Davis CS, Wenzel RP (1995) The natural history of the systemic inflammatory response syndrome (SIRS). A prospective study. JAMA 273(2):117–123

    Article  PubMed  CAS  Google Scholar 

  • Reece T, Ellman P, Maxey T, Crosby I, Warren P, Chong T, LeGallo RD, Linden J, Kern JA, Tribble CG et al (2005) Adenosine A2A receptor activation reduces inflammation and preserves pulmonary function in an in vivo model of lung transplantation. J Thorac Cardiovasc Surg 129(5):1137–1143

    Article  PubMed  CAS  Google Scholar 

  • Reeves JJ, Jones CA, Sheehan MJ, Vardey CJ, Whelan CJ (1997) Adenosine A3 receptors promote degranulation of rat mast cells both in vitro and in vivo. Inflamm Res 46(5):180–184

    Article  PubMed  CAS  Google Scholar 

  • Reeves JJ, Harris CA, Hayes BP, Butchers PR, Sheehan MJ (2000) Studies on the effects of adenosine A3 receptor stimulation on human eosinophils isolated from non-asthmatic or asthmatic donors. Inflamm Res 49(12):666–672

    Article  PubMed  CAS  Google Scholar 

  • Regan SE, Broad M, Byford AM, Lankford AR, Cerniway RJ, Mayo MW, Matherne GP (2003) A1 adenosine receptor overexpression attenuates ischemia-reperfusion-induced apoptosis and caspase 3 activity. Am J Physiol – Heart Circ Physiol 284(3):H859–H866

    Google Scholar 

  • Rimmer J, Peake HL, Santos CM, Lean M, Bardin P, Robson R, Haumann B, Loehrer F, Handel ML (2007) Targeting adenosine receptors in the treatment of allergic rhinitis: a randomized, double-blind, placebo-controlled study. Clin Exp Allergy 37(1):8–14

    Google Scholar 

  • Rivkees SA (1994) Localization and characterization of adenosine receptor expression in rat testis. Endocrinology 135(6):2307–2313

    Article  PubMed  CAS  Google Scholar 

  • Rivo J, Zeira E, Galun E, Einav S, Linden J, Matot I (2007) Attenuation of reperfusion lung injury and apoptosis by A2A adenosine receptor activation is associated with modulation of Bcl-2 and Bax expression and activation of extracellular signal-regulated kinases. Shock 27(3):266–273

    Article  PubMed  CAS  Google Scholar 

  • Ryzhov S, Goldstein AE, Matafonov A, Zeng D, Biaggioni I, Feoktistov I (2004) 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. J Immunol 172(12):7726–7733

    PubMed  CAS  Google Scholar 

  • Sajjadi FG, Firestein GS (1993) cDNA cloning and sequence analysis of the human A3 adenosine receptor. Biochim Biophys Acta 1179(1):105–107

    Article  PubMed  CAS  Google Scholar 

  • Sajjadi FG, Takabayashi K, Foster AC, Domingo RC, Firestein GS (1996) Inhibition of TNF-alpha expression by adenosine: role of A3 adenosine receptors. J Immunol 156(9):3435–3442

    PubMed  CAS  Google Scholar 

  • Salvatore CA, Jacobson MA, Taylor HE, Linden J, Johnson RG (1993) Molecular cloning and characterization of the human A3 adenosine receptor. Proc Natl Acad Sci 90(21):10365–10369

    Article  PubMed  CAS  Google Scholar 

  • Salvatore CA, Tilley SL, Latour AM, Fletcher DS, Koller BH, Jacobson MA (2000) Disruption of the A3 adenosine receptor gene in mice and its effect on stimulated inflammatory cells. J Biol Chem 275(6):4429–4434

    Article  PubMed  CAS  Google Scholar 

  • Schepp CP, Reutershan J (2008) Bench-to-bedside review: adenosine receptors – promising targets in acute lung injury? Crit Care 12(5):226

    Article  PubMed  Google Scholar 

  • Sharma AK, Fernandez LG, Awad AS, Kron IL, Laubach VE (2007) Proinflammatory response of alveolar epithelial cells is enhanced by alveolar macrophage-produced TNF-alpha during pulmonary ischemia-reperfusion injury. Am J Physiol Lung Cell Mol Physiol 293(1):L105–L113

    Article  PubMed  CAS  Google Scholar 

  • Shepherd RK, Duling BR (1996) Inosine-induced vasoconstriction is mediated by histamine and thromboxane derived from mast cells. Am J Physiol 270(2 Pt 2):H560–H566

    PubMed  CAS  Google Scholar 

  • Shepherd RK, Linden J, Duling BR (1996) Adenosine-induced vasoconstriction in vivo. Role of the mast cell and A3 adenosine receptor. Circ Res 78(4):627–634

    Google Scholar 

  • Shneyvays V, Nawrath H, Jacobson KA, Shainberg A (1998) Induction of apoptosis in cardiac myocytes by an A3 adenosine receptor agonist. Exp Cell Res 243(2):383–397

    Article  PubMed  CAS  Google Scholar 

  • Shneyvays V, Jacobson KA, Li AH, Nawrath H, Zinman T, Isaac A, Shainberg A (2000) Induction of apoptosis in rat cardiocytes by A3 adenosine receptor activation and its suppression by isoproterenol. Exp Cell Res 257(1):111–126

    Article  PubMed  CAS  Google Scholar 

  • Silberstein DS (1995) Eosinophil function in health and disease. Crit Rev Oncol Hematol 19(1):47–77

    Article  PubMed  CAS  Google Scholar 

  • Slutsky AS (1999) Lung injury caused by mechanical ventilation. Chest 116(1 Suppl):9S–15S

    PubMed  CAS  Google Scholar 

  • Spicuzza L, Bonfiglio C, Polosa R (2003) Research applications and implications of adenosine in diseased airways. Trends Pharmacol Sci 24(8):409–413

    Article  PubMed  CAS  Google Scholar 

  • Spruntulis LM, Broadley KJ (2001) A3 receptors mediate rapid inflammatory cell influx into the lungs of sensitized guinea-pigs. Clin Exp Allergy 31(6):943–951

    Article  PubMed  CAS  Google Scholar 

  • Stallion A, Kou TD, Latifi SQ, Miller KA, Dahms BB, Dudgeon DL, Levine AD (2005) Ischemia/reperfusion: a clinically relevant model of intestinal injury yielding systemic inflammation. J Pediatr Surg 40(3):470–477

    Article  PubMed  Google Scholar 

  • Szabó C, Scott GS, Virág L, Egnaczyk G, Salzman AL, Shanley TP, Haskó G (1998) Suppression of macrophage inflammatory protein (MIP)-1alpha production and collagen-induced arthritis by adenosine receptor agonists. Br J Pharmacol 125(2):379–387

    Article  PubMed  Google Scholar 

  • Thorne JR, Danahay H, Broadley KJ (1996) Analysis of the bronchoconstrictor responses to adenosine receptor agonists in sensitized guinea-pig lungs and trachea. Eur J Pharmacol 316(2–3):263–271

    Article  PubMed  CAS  Google Scholar 

  • Tilley SL, Wagoner VA, Salvatore CA, Jacobson MA, Koller BH (2000) Adenosine and inosine increase cutaneous vasopermeability by activating A3 receptors on mast cells. J Clin Invest 105(3):361–367

    Article  PubMed  CAS  Google Scholar 

  • Tilley SL, Tsai M, Williams CM, Wang ZS, Erikson CJ, Galli SJ, Koller BH (2003) Identification of A3 receptor- and mast cell-dependent and -independent components of adenosine-mediated airway responsiveness in mice. J Immunol 171(1):331–337

    PubMed  CAS  Google Scholar 

  • Toledo-Pereyra LH, Toledo AH, Walsh J, Lopez-Neblina F (2004) Molecular signaling pathways in ischemia/reperfusion. Exp Clin Transplant 2(1):174–177

    PubMed  Google Scholar 

  • Tracey WR, Magee W, Masamune H, Kennedy SP, Knight DR, Buchholz RA, Hill RJ (1997) Selective adenosine A3 receptor stimulation reduces ischemic myocardial injury in the rabbit heart. Cardiovasc Res 33(2):410–415

    Article  PubMed  CAS  Google Scholar 

  • Van der Bruggen T, Koenderman L (1996) Signal transduction in eosinophils. Clin Exp Allergy 26(8):880–891

    Article  PubMed  Google Scholar 

  • Van Schaick EA, Jacobson KA, Kim HO, IJzerman AP, Danhof M (1996) Hemodynamic effects and histamine release elicited by the selective adenosine A3 receptor agonist 2-Cl-IB-MECA in conscious rats. Eur J Pharmacol 308(3):311–314

    Article  PubMed  Google Scholar 

  • Varani K, Caramori G, Vincenzi F, Adcock I, Casolari P, Leung E, Maclennan S, Gessi S, Morello S, Barnes PJ, Ito K, Chung KF, Cavallesco G, Azzena G, Papi A, Borea PA (2006) Alteration of adenosine receptors in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 173(4):398–406

    Article  PubMed  CAS  Google Scholar 

  • Walker BA (1996) Effects of adenosine on guinea pig pulmonary eosinophils. Inflammation 20(1):11–21

    Article  PubMed  CAS  Google Scholar 

  • Walker BA, Jacobson MA, Knight DA, Salvatore CA, Weir T, Zhou D, Bai TR (1997) Adenosine A3 receptor expression and function in eosinophils. Am J Respir Cell Mol Biol 16(5):531–537

    PubMed  CAS  Google Scholar 

  • Ware LB, Matthay MA (2000) The acute respiratory distress syndrome. N Eng J Med 342(18):1334–1349

    Article  CAS  Google Scholar 

  • Williams EA, Evans TW, Goldstraw P (1996) Acute lung injury following lung resection: is one lung anaesthesia to blame? Thorax 51(2):114–116

    Article  PubMed  CAS  Google Scholar 

  • Wilson WC, Laborde PR, Benumof JL, Taylor R, Swetland JF (1993) Reperfusion injury and exhaled hydrogen peroxide. Anesth Analg 77(5):963–970

    Article  PubMed  CAS  Google Scholar 

  • Xia Z, Dickens M, Raingeaud J, Davis RJ, Greenberg ME (1995) Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 270(5240):1326–1331

    Article  PubMed  CAS  Google Scholar 

  • Yasuhara H (2005) Acute mesenteric ischemia: the challenge of gastroenterology. Surg Today 35(3):185–195

    Article  PubMed  Google Scholar 

  • Young HW, Molina JG, Dimina D, Zhong H, Jacobson M, Chan LN, Chan TS, Lee JJ, Blackburn MR (2004) A3 adenosine receptor signaling contributes to airway inflammation and mucus production in adenosine deaminase-deficient mice. J Immunol 173(2):1380–1389

    PubMed  CAS  Google Scholar 

  • Yue TL, Wang C, Gu JL, Ma XL, Kumar S, Lee JC, Feuerstein GZ, Thomas H, Maleeff B, Ohlstein EH (2000) Inhibition of extracellular signal- regulated kinase enhances ischemia/reoxygenationinduced apoptosis in cultured cardiac myocytes and exaggerates reperfusion injury in isolated perfused heart. Circ Res 86(6):692–699

    PubMed  CAS  Google Scholar 

  • Zhao Z, Francis C, Ravid K (1999) Characterization of the mouse A3 adenosine receptor gene: exon/intron organization and promoter activity. Genomics 57(1):152–155

    Article  PubMed  CAS  Google Scholar 

  • Zhao M, Fernandez LG, Doctor A, Sharma AK, Zarbock A, Tribble CG, Kron IL, Laubach VE (2006) Alveolar macrophage activation is a key initiation signal for acute lung ischemia-reperfusion injury. Am J Physiol Lung Cell Mol Physiol 291(5):L1018–L1026

    Article  PubMed  CAS  Google Scholar 

  • Zhong H, Shlykov SG, Molina JG, Sanborn BM, Jacobson MA, Tilley SL, Blackburn MR (2003) Activation of murine lung mast cells by the adenosine A3 receptor. J Immunol 171(1):338–345

    PubMed  CAS  Google Scholar 

  • Zhong H, Belardinelli L, Maa T, Feoktistov I, Biaggioni I, Zeng DA (2004) A(2B) Adenosine receptors increase cytokine release by bronchial smooth muscle cells. Am J Respir Cell Mol Biol 30(1):118–125

    Article  PubMed  CAS  Google Scholar 

  • Zhou QY, Chuanyi L, Olah ME, Johnson RA, Stiles GL, Civelli O (1992) Molecular cloning and characterization of an adenosine receptor: the A3 adenosine receptor. Proc Natl Acad Sci 89(16):7432–7436

    Article  PubMed  CAS  Google Scholar 

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    Yifat Klein & Idit Matot

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    Pier Andrea Borea

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Klein, Y., Matot, I. (2010). A3 Adenosine Receptor in the Pulmonary System. In: Borea, P. (eds) A3 Adenosine Receptors from Cell Biology to Pharmacology and Therapeutics. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3144-0_11

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