Skip to main content
SpringerLink
Log in

Adenosine Receptors and Asthma

  • Chapter
  • First Online:
Adenosine Receptors in Health and Disease

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 193))

Abstract

The pathophysiological processes underlying respiratory diseases like asthma are complex, resulting in an overwhelming choice of potential targets for the novel treatment of this disease. Despite this complexity, asthmatic subjects are uniquely sensitive to a range of substances like adenosine, thought to act indirectly to evoke changes in respiratory mechanics and in the underlying pathology, and thereby to offer novel insights into the pathophysiology of this disease. Adenosine is of particular interest because this substance is produced endogenously by many cells during hypoxia, stress, allergic stimulation, and exercise. Extracellular adenosine can be measured in significant concentrations within the airways; can be shown to activate adenosine receptor (AR) subtypes on lung resident cells and migrating inflammatory cells, thereby altering their function, and could therefore play a significant role in this disease. Many preclinical in vitro and in vivo studies have documented the roles of the various AR subtypes in regulating cell function and how they might have a beneficial impact in disease models. Agonists and antagonists of some of these receptor subtypes have been developed and have progressed to clinical studies in order to evaluate their potential as novel antiasthma drugs. In this chapter, we will highlight the roles of adenosine and AR subtypes in many of the characteristic features of asthma: airway obstruction, inflammation, bronchial hyperresponsiveness and remodeling. We will also discuss the merit of targeting each receptor subtype in the development of novel antiasthma drugs.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 389.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 499.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 549.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

AC:

Adenylate cyclase

ADA:

Adenosine deaminase

ADP:

Adenosine diphosphate

AK:

Adenosine kinase

AMP:

Adenosine monophosphate

AR:

Adenosine receptor

ATP:

Adenosine triphosphate

BAL:

Bronchoalveolar lavage

BHR:

Bronchial hyperresponsiveness

BMMC:

Bone marrow-derived mast cell

CFTR:

Cystic fibrosis transmembrane conductance regulator

CPA:

Cyclopentyadenosine

CXCR4:

Chemokine receptor 4

cyto-5′-NT:

Cytosolic form of nucleotidase

DPCPX:

1,3-Dipropyl-8-cyclopentylxanthine

EAR:

Early asthmatic response

ecto-5′-NT:

Ecto-5′-nucleotidase

FEV1:

Forced expiratory volume in 1 s

fMLP:

Formyl-Met–Leu–Phe

HBEC:

Human bronchial epithelial cell

HPRT:

Hypoxanthine phosphoribosyltransferase

ICS:

Inhaled corticosteroids

IgE:

Immunoglobulin E

IL:

Interleukin

IMP:

Inosine monophosphate

iNOS:

Inducible nitric oxide synthase

LABA:

Long-acting beta-adrenoceptor agonist

LAR:

Late asthmatic response

LPS:

Lipopolysaccharide

MCP-1:

Monocyte chemotactic protein-1

NADPH:

Nicotinamide adenine dinucleotide phosphate

NF-κB:

Nuclear factor kappa B

NTPDase:

Nucleoside triphosphate diphosphohydrolase

PC:

Provocative concentration

PEFR:

Peak expiratory flow rate

PDE:

Phosphodiesterase

PG:

Prostaglandin

PLC:

Phospholipase C

PNC:

Purine nucleotide cycle

PNP:

Purine nucleoside phosphorylase

POC:

Proof of concept

RASON:

Respiratory antisense oligonucleotide

RT-PCR:

Reverse transcriptase polymerase chain reaction

SAHH:

S-Adenosylhomocysteine hydrolase

TNF:

Tumor necrosis factor

VEGF:

Vascular endothelium growth factor

References

  • 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:L990–L997

    PubMed  CAS  Google Scholar 

  • Ali S, Mustafa SJ, Metzger WJ (1992) Adenosine-induced bronchoconstriction in an allergic rabbit model: antagonism by theophylline aerosol. Agents Actions 37:165–167

    PubMed  CAS  Google Scholar 

  • Ali S, Mustafa SJ, Metzger WJ (1994a) Adenosine receptor-mediated bronchoconstriction and bronchial hyper-responsiveness in allergic rabbit model. Am J Physiol 266(Lung Cell Mol Physiol 10):L271–L277

    Google Scholar 

  • Ali S, Mustafa SJ, Metzger WJ (1994b) Adenosine-induced bronchoconstriction and contraction of airway smooth muscle from allergic rabbits with late-phase airway obstruction: evidence for an inducible adenosine A1 receptor. J Pharmacol Exp Ther 268:1328–1334

    PubMed  CAS  Google Scholar 

  • Allen-Gipson DS, Wong J, Spurzem JR, Sisson JH, Wyatt TA (2005) Adenosine A2A receptors promote adenosine-stimulated wound healing in bronchial epithelial cells. Am J Physiol Lung Cell Mol Physiol 290:L849–L855

    PubMed  Google Scholar 

  • An SS, Bai TR, Bates JH, Black JL, Brown RH, Brusasco V, Chitano P, Deng L, Dowell M, Eidelman DH, Fabry B, Fairbank NJ, Ford LE, Fredberg JJ, Gerthoffer WT, Gilbert SH, Gosens R, Gunst SJ, Halayko AJ, Ingram RH, Irvin CG, James AL, Janssen LJ, King GG, Knight DA, Lauzon AM, Lakser OJ, Ludwig MS, Lutchen KR, Maksym GN, Martin JG, Mauad T, McParland BE, Mijailovich SM, Mitchell HW, Mitchell RW, Mitzner W, Murphy TM, Pare PD, Pellegrino R, Sanderson MJ, Schellenberg RR, Seow CY, Silveira PS, Smith PG, Solway J, Stephens NL, Sterk PJ, Stewart AG, Tang DD, Tepper RS, Tran T, Wang L (2007) Airway smooth muscle dynamics: a common pathway of airway obstruction in asthma. Eur Respir J 29:834–860

    PubMed  CAS  Google Scholar 

  • Apasov S, Koshiba M, Redegeld F, Sitkovsky MV (1995) Role of extracellular ATP and P1 and P2 classes of purinergic receptors in T-cell development and cytotoxic T lymphocyte effector functions. Immunol Rev 146:5–19

    PubMed  CAS  Google Scholar 

  • Avital A, Springer C, Bar-Yishay E, Godfrey S (1995) Adenosine, methacholine, and exercise challenges in children with asthma or paediatric chronic obstructive pulmonary disease. Thorax 50:511–516

    PubMed  CAS  Google Scholar 

  • Ball HA, Sandrasagra A, Tang L, Scott MV, Wild J, Nyce JW (2003) Clinical potential of respirable antisense oligonucleotides (RASONs) in asthma. Am J Pharmacogenomics 3:97–106

    PubMed  CAS  Google Scholar 

  • Baraldi PG, Cacciari B, Romagnoli R, Merighi S, Varani K, Borea PA, Spalluto G (2000) A3 adenosine receptor ligands: history and perspectives. Med Res Rev 20:103–128

    PubMed  CAS  Google Scholar 

  • Barrett RJ (1996) Realizing the potential of adenosine-receptor-based therapeutics. Proc West Pharmacol Soc 39:61–66

    PubMed  CAS  Google Scholar 

  • Beier KC, Kallinich T, Hamelmann E (2007) T-cell co-stimulatory molecules: novel targets for the treatment of allergic airway disease. Eur Respir J 30:383–390

    PubMed  CAS  Google Scholar 

  • Belda J, Casan P, Martínez C, Margarit G, Giner J, Homs R, Granel C, Sanchis J (2005) Bronchial plasma exudation after adenosine monophosphate or methacholine challenge. J Asthma 42:885–890

    PubMed  CAS  Google Scholar 

  • Berman AR, Togias AG, Skloot G, Proud D (1995) Allergen-induced hyperresponsiveness to bradykinin is more pronounced than that to methacholine. J Appl Physiol 78:1844–1852

    PubMed  CAS  Google Scholar 

  • Bertolet BD, Belardinelli L, Franco EA, Nichols WW, Kerensky RA, Hill JA (1996) Selective attenuation by N-0861 (N 6-endonorboran-2-yl-9-methyladenine) of cardiac A1 adenosine receptor-mediated effects in humans. Circulation 93:1871–1876

    PubMed  CAS  Google Scholar 

  • Beukers MW, Meurs I, Ijzerman AP (2006) Structure–affinity relationships of adenosine A2B receptor ligands. Med Res Rev 26:667–698

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Blackburn MR, Volmer JB, Thrasher JL, Zhong H, Crosby JR, Lee JJ, Kellems RE (2000) Metabolic consequences of adenosine deaminase deficiency in mice are associated with defects in alveogenesis, pulmonary inflammation, and airway obstruction. J Exp Med 192:159–170

    PubMed  CAS  Google Scholar 

  • Blackburn MR, Lee CG, Young HWJ, Zhu Z, Chunn JL, Kang MJ, Banerjee SK, Elias JA (2003) Adenosine mediates IL-13-induced inflammation and remodeling in the lung and interacts in an IL-13-adenosine amplification pathway. J Clin Invest 112:332–344

    PubMed  CAS  Google Scholar 

  • Bochenek G, Nizankowska E, Gielicz A, Szczeklik A (2008) Mast cell activation after adenosine inhalation challenge in patients with bronchial asthma. Allergy 63:140–141

    PubMed  CAS  Google Scholar 

  • Bond RA, Spina D, Parra S, Page CP (2007) Getting to the heart of asthma: can “beta blockers” be useful to treat asthma? Pharmacol Ther 115:360–374

    PubMed  CAS  Google Scholar 

  • Bonneau O, Wyss D, Ferretti S, Blaydon C, Stevenson CS, Trifilieff A (2006) Effect of adenosine A2A receptor activation in murine models of respiratory disorders. Am J Physiol Lung Cell Mol Physiol 290:L1036–L1043

    PubMed  CAS  Google Scholar 

  • Breschi MC, Blandizzi C, Fogli S, Martinelli C, Adinolfi B, Calderone V, Camici M, Martinotti E, Nieri P (2007) In vivo adenosine A(2B) receptor desensitization in guinea-pig airway smooth muscle: implications for asthma. Eur J Pharmacol 575:149–157

    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, O’Connor BJ (2008) Elevated expression of adenosine A1 receptor in bronchial biopsy specimens from asthmatic subjects. Eur Respir J 31:311–319

    PubMed  CAS  Google Scholar 

  • Bshesh K, Zhao B, Spight D, Biaggioni I, Feokistov I, Denenberg A, Wong HR, Shanley TP (2002) The A2A receptor mediates an endogenous regulatory pathway of cytokine expression in THP-1 cells. J Leukoc Biol 72:1027–1036

    PubMed  CAS  Google Scholar 

  • Bucchioni E, Csoma Z, Allegra L, Chung KF, Barnes PJ, Kharitonov SA (2004) Adenosine 5′-monophosphate increases levels of leukotrienes in breath condensate in asthma. Respir Med 98:651–655

    PubMed  CAS  Google Scholar 

  • Busse WW, Lemanske RF Jr (2001) Asthma. N Engl J Med 344:350–362

    PubMed  CAS  Google Scholar 

  • Chuaychoo B, Lee MG, Kollarik M, Pullmann R Jr, Undem BJ (2006) Evidence for both adenosine A1 and A2A receptors activating single vagal sensory C-fibres in guinea pig lungs. J Physiol 575:481–490

    PubMed  CAS  Google Scholar 

  • Chunn JL, Young HW, Banerjee SK, Colasurdo GN, Blackburn MR (2001) Adenosine-dependent airway inflammation and hyperresponsiveness in partially adenosine deaminase-deficient mice. J Immunol 167:4676–4685

    PubMed  CAS  Google Scholar 

  • Clancy JP, Ruiz FE, Sorscher EJ (1999) Adenosine and its nucleotides activate wild-type and R117H CFTR through an A2B receptor-coupled pathway. Am J Physiol 276(2 Pt 1): C361–C369

    PubMed  CAS  Google Scholar 

  • Clark AN, Youkey R, Liu X, Jia L, Blatt R, Day Y-J, Sullivan GW, Linden J, Tucker, AL (2007) A1 adenosine receptor activation promotes angiogenesis and release of VEGF from monocytes. Circ Res 101:1–9

    Google Scholar 

  • Cockcroft DW, Davis BE (2006) Mechanisms of airway hyperresponsiveness. J Allergy Clin Immunol 118:551–559

    PubMed  CAS  Google Scholar 

  • Cohn L, Elias JA, Chupp GL (2004) Asthma: mechanisms of disease persistence and progression. Annu Rev Immunol 22:789–815

    PubMed  CAS  Google Scholar 

  • Crimi N, Palermo F, Oliveri R, Maccarrone C, Palermo B, Vancheri C, Polosa R, Mistretta A (1988) Enhancing effect of dipyridamole inhalation on adenosine-induced bronchospasm in asthmatic patients. Allergy 43:179–183

    PubMed  CAS  Google Scholar 

  • Crimi N, Palermo F, Oliveri R, Palermo B, Polosa R, Mistretta A (1992) Protection of nedocromil sodium on bronchoconstriction induced by inhaled neurokinin A (NKA) in asthmatic patients. Clin Exp Allergy 22:75–81

    PubMed  CAS  Google Scholar 

  • Cronstein BN (2006) Adenosine receptors and wound healing, revised. Sci World J 6:984–991

    CAS  Google Scholar 

  • Cronstein BN, Kramer SB, Weissmann G, Hirschhorn R (1983) Adenosine: a physiological modulator of superoxide anion generation by human neutrophils. J Exp Med 158:1160–1177

    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 85:1150–1157

    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 148:2201–2206

    PubMed  CAS  Google Scholar 

  • Csoma Z, Huszár E, Vizi E, Vass G, Szabó Z, Herjavecz I, Kollai M, Horváth I (2005) Adenosine level in exhaled breath increases during exercise-induced bronchoconstriction. Eur Respir J 25:873–878

    PubMed  CAS  Google Scholar 

  • Cushley MJ, Tattersfield AE, Holgate ST (1983) Inhaled adenosine and guanosine on airway resistance in normal and asthmatic subjects. Br J Clin Pharmacol 15:161–165

    PubMed  CAS  Google Scholar 

  • Dahlen S.-E, Hansson G, Hedqvist P, Bjorck T, Granstrom E, Dahlen B (1983) Allergen challenge of lung tissue from asthmatics elicits bronchial contraction that correlates with the release of leukotrienes C4, D4, and E4. Proc Natl Acad Sci USA 80:1712–1716

    PubMed  CAS  Google Scholar 

  • de Meer G, Heederik D, Postma DS (2002) Bronchial responsiveness to adenosine 5′-monophosphate (AMP) and methacholine differ in their relationship with airway allergy and baseline FEV1. Am J Respir Crit Care Med 165:327–331

    PubMed  Google Scholar 

  • Deussen A (2000) Metabolic flux rates of adenosine in the heart. Naunyn–Schmiedeberg’s Arch Pharmacol 362:351–363

    CAS  Google Scholar 

  • Dittrich HC, Gupta DK, Hack TC, Dowling T, Callahan J, Thomson S (2007) The effect of KW-3902, an adenosine A1 receptor antagonist, on renal function and renal plasma flow in ambulatory patients with heart failure and renal impairment. J Card Failure 13:609–617

    CAS  Google Scholar 

  • Doggrell SA (2005) BG-9928 Biogen Idec. Curr Opin Investig Drugs 6: 962–968

    PubMed  CAS  Google Scholar 

  • Driver AG, Kukoly CA, Metzger WJ, Mustafa SJ (1991) Bronchial challenge with adenosine causes the release of serum neutrophil chemotactic factor in asthma. Am Rev Respir Dis 143:1002–1007

    PubMed  CAS  Google Scholar 

  • Driver AG, Kukoly CA, Ali S, Mustafa SJ (1993) Adenosine in bronchoalveolar lavage fluid in asthma. Am Rev Respir Dis 148:91–97

    PubMed  CAS  Google Scholar 

  • el-Hashim A, D’Agostino B, Matera MG, Page CP (1996) Characterization of adenosine receptors involved in adenosine-induced bronchoconstriction in allergic rabbits. Br J Pharmacol 119:1262–1268

    PubMed  CAS  Google Scholar 

  • Eltzschig HK, Thompson LF, Karhausen J, Cotta RJ, Ibla JC, Robson SC, Colgan SP (2004) Endogenous adenosine produced during hypoxia attenuates neutrophil accumulation: coordination by extracellular nucleotide metabolism. Blood 104:3986–3992

    PubMed  CAS  Google Scholar 

  • Ethier MF, Madison JM (2006) Adenosine A1 receptors mediate mobilization of calcium in human bronchial smooth muscle cells. Am J Respir Cell Mol Biol 35:496–502

    PubMed  CAS  Google Scholar 

  • Ezeamuzie CI (2001) Involvement of A(3) receptors in the potentiation by adenosine of the inhibitory effect of theophylline on human eosinophil degranulation: possible novel mechanism of the anti-inflammatory action of theophylline. Biochem Pharmacol 61:1551–1559

    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 127:188–194

    PubMed  CAS  Google Scholar 

  • Fan M, Mustafa SJ (2002) Adenosine-mediated bronchoconstriction and lung inflammation in an allergic mouse model. Pul Pharmacol Ther 15:147–155

    CAS  Google Scholar 

  • Fan M, Mustafa SJ (2006) Role of adenosine in airway inflammation in an allergic mouse model of asthma. Int Immunopharmacol 6:36–45

    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:L1012–L1019

    PubMed  CAS  Google Scholar 

  • Feoktistov I, Biaggioni I (1995) Adenosine A2b receptors evoke interleukin-8 secretion in human mast cells. An enprofylline-sensitive mechanism with implications for asthma. J Clin Invest 96:1979–1986

    CAS  Google Scholar 

  • Feoktistov I, Goldstein AE, Biaggioni I (1999) Role of p38 mitogen-activated protein kinase and extracellular signal-regulated protein kinase in adenosine A2B receptor-mediated interleukin-8 production in human mast cells. Mol Pharmacol 55:726–734

    PubMed  CAS  Google Scholar 

  • Feoktistov I, Garland EM, Goldstein AE, Zeng D, Belardinelli L, Wells JN, Biaggioni I (2001) Inhibition of human mast cell activation with the novel selective adenosine A(2B) receptor antagonist 3-isobutyl-8-pyrrolidinoxanthine (IPDX)(2). Biochem Pharmacol 62:1163–1173

    PubMed  CAS  Google Scholar 

  • Fishman P, Bar-Yehuda S (2003) Pharmacology and therapeutic applications of A3 receptor subtype. Curr Top Med Chem 3:463–469

    PubMed  CAS  Google Scholar 

  • Fozard JR, Ellis KM, Villela Dantas MF, Tigani B, Mazzoni L (2002) Effects of CGS 21680, a selective adenosine A2A receptor agonist, on allergic airways inflammation in the rat. Eur J Pharmacol 438:183–188

    PubMed  CAS  Google Scholar 

  • Fredholm BB (2007) Adenosine, an endogenous distress signal, modulates tissue damage and repair. Cell Death Diff 14:1315–1323

    CAS  Google Scholar 

  • Fredholm BB, IJzerman AP, Jacobson KA, Klotz KN, Linden J (2001) International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacol Rev 53:527–552

    CAS  Google Scholar 

  • Gao Z-G, Jacobson KA (2007) Emerging adenosine receptor agonists. Expert Opin Emerg Drugs 12:479–492

    PubMed  CAS  Google Scholar 

  • Gaspardone A, Crea F, Iamele M, Tomai F, Versaci F, Pellegrino A, Chiariello L, Gioffre PA (1993) Bamiphylline improves exercise-induced myocardial ischemia through a novel mechanism of action. Circulation 88:502–508

    PubMed  CAS  Google Scholar 

  • Gessi S, Merighi S, Varani K, Leung E, Lennan SM, Borea PA (2008) The A3 adenosine receptor: an enigmatic player in cell biology. Pharmacol Ther 117:123–140

    PubMed  CAS  Google Scholar 

  • Gil FR, Lauzon AM (2007) Smooth muscle molecular mechanics in airway hyperresponsiveness and asthma. Can J Physiol Pharmacol 85:133–140

    PubMed  CAS  Google Scholar 

  • Givertz MM, Massie BM, Fields TK, Pearson LL, Dittrich HC (2007) The effect of KW-3902, an adenosine A1-receptor antagonist, on diuresis and renal function in patients with acute decompensated heart failure and renal impairment or diuretic resistance. J Am Coll Cardiol 50:1551–1560

    PubMed  CAS  Google Scholar 

  • Gottlieb SS, Brater C, Thomas I, Havranek E, Bourge R, Goldman S, Dyer F, Gomez M, Bennett D, Ticho B, Beckman E, Abraham WT (2002) BG9719 (CVT-124), an A1 adenosine receptor antagonist, protects against the decline in renal function observed with diuretic therapy. Circulation 105:1348–1353

    PubMed  CAS  Google Scholar 

  • Greenberg B, Ignatius T, Banish D, Goldman S, Havranek E, Massie BM, Zhu Y, Ticho B, Abraham WT (2007) Effects of multiple oral doses of an A1 adenosine receptor antagonist, BG 9928, in patients with heart failure. J Am Coll Cardiol 50:600–606

    PubMed  CAS  Google Scholar 

  • Gunther GR, Herring MB (1991) Inhibition of neutrophil superoxide production by adenosine released from vascular endothelial cells. Ann Vasc Surg 5:325–330

    PubMed  CAS  Google Scholar 

  • Hammad H, Lambrecht BN (2007) Lung dendritic cell migration. Adv Immunol 93:265–278

    PubMed  CAS  Google Scholar 

  • Hannon JP, Tigani B, Wolber C, Williams I, Mazzoni L, Howes C, Fozard JR (2002) Evidence for an atypical receptor mediating the augmented bronchoconstrictor response to adenosine induced by allergen challenge in actively sensitized Brown Norway rats. Br J Pharmacol 135:685–696

    PubMed  CAS  Google Scholar 

  • Hasko G, Cronstein BN (2004) Adenosine: an endogenous regulator of innate immunity. Trends Immunol 25:33–39

    PubMed  CAS  Google Scholar 

  • Hasko G, Kuhel DG, Nemeth ZH, Mabley JG, Stachlewitz RF, Virag L, Lohinai Z, Southan GJ, Salzman AL, Szabo C (2000) Inosine inhibits inflammatory cytokine production by a posttranscriptional mechanism and protects against endotoxin-induced shock. J Immunol 164:1013–1019

    PubMed  CAS  Google Scholar 

  • Hasko G, Sitkovsky MV, Szabo C (2004) Immunomodulatory and neuroprotective effects of inosine. Trends Pharmacol Sci 25:152–157

    PubMed  CAS  Google Scholar 

  • Hess S (2001) Recent advances in adenosine receptor antagonist research. Expert Opin Ther Pat 11:1533–1561

    CAS  Google Scholar 

  • Holgate ST (2002) Adenosine provocation: a new test for allergic type airway inflammation. Am J Respir Crit Care Med 165:317–319

    PubMed  Google Scholar 

  • Holgate ST (2007) The epithelium takes centre stage in asthma and atopic dermatitis. Trends Immunol 28:248–251

    PubMed  CAS  Google Scholar 

  • Hong JL, Ho CY, Kwong K, Lee LY (1998) Activation of pulmonary C fibres by adenosine in anaesthetized rats: role of adenosine A1 receptors. J Physiol 508:109–118

    PubMed  CAS  Google Scholar 

  • Hua X, Erikson CJ, Chason KD, Rosebrock CN, Deshpande DA, Penn RB, Tilley SL (2007a) Involvement of A1 adenosine receptors and neural pathways in adenosine-induced bronchoconstriction in mice. Am J Physiol Lung Cell Mol Physiol 293:L25–L32

    PubMed  CAS  Google Scholar 

  • Hua X, Kovarova M, Chason KD, Nguyen M, Koller BH, Tilley SL (2007b) Enhanced mast cell activation in mice deficient in the A2b adenosine receptor. J Exp Med 204:117–128

    PubMed  CAS  Google Scholar 

  • Huang P, Lazarowski ER, Tarran R, Milgram SL, Boucher RC, Stutts MJ (2001) Compartmentalized autocrine signaling to cystic fibrosis transmembrane conductance regulator at the apical membrane of airway epithelial cells. Proc Natl Acad Sci USA 98:14120–14125

    PubMed  CAS  Google Scholar 

  • Hyde RJ, Cass CE, Young JD, Baldwin SA (2001) The ENT family of eukaryote nucleoside and nucleobase transporters: recent advances in the investigation of structure/function relationships and the identification of novel isoforms. Mol Membr Biol 18:53–63

    PubMed  CAS  Google Scholar 

  • Ihre E, Gyllfors P, Gustafsson LE, Kumlin M, Dahlén B (2006) Early rise in exhaled nitric oxide and mast cell activation in repeated low-dose allergen challenge. Eur Respir J 27:1152–1159

    PubMed  CAS  Google Scholar 

  • Jacobsen EA, Ochkur SI, Lee NA, Lee JJ (2007) Eosinophils and asthma. Curr Allergy Asthma Rep 7:18–26

    PubMed  CAS  Google Scholar 

  • Jarjour NN, Kelly EAB (2002) Pathogenesis of asthma. Med Clin North Am 86:925–936

    PubMed  CAS  Google Scholar 

  • Johnson HG, McNee ML (1985) Adenosine-induced secretion in the canine trachea: modification by methylxanthines and adenosine derivatives. Br J Pharmacol 86:63–67

    PubMed  CAS  Google Scholar 

  • Kaczmarek E, Koziak K, Sevigny J, Siegel JB, Anrather J, Beaudoin AR, Bach FH, Robson SC (1996) Identification and characterization of CD39/vascular ATP diphosphohydrolase. J Biol Chem 271:33116–33122

    PubMed  CAS  Google Scholar 

  • Kalk P, Eggert B, Relle K, Godes M, Heiden S, Sharkovska Y, Fischer Y, Ziegler D, Bielenberg G-W, Hocher B (2007) The adenosine A1 receptor antagonist SLV320 reduces myocardial fibrosis in rats with 5/6 nephrectomy without affecting blood pressure. Br J Pharmacol 151:1025–1032

    PubMed  CAS  Google Scholar 

  • Kallinich T, Beier KC, Wahn U, Stock P, Hamelmann E (2007) T-cell co-stimulatory molecules: their role in allergic immune reactions. Eur Respir J 29:1246–1255

    PubMed  CAS  Google Scholar 

  • Keir S, Boswell-Smith V, Spina D, Page C (2006) Mechanism of adenosine-induced airways obstruction in allergic guinea pigs. Br J Pharmacol 47:720–728

    Google Scholar 

  • Ketchell RI, Jensen MW, Lumley P, Wright AM, Allenby MI, O’Connor BJ (2002) Rapid effect of inhaled fluticasone propionate on airway responsiveness to adenosine 5′-monophosphate in mild asthma. J Allergy Clin Immunol 110:603–606

    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 62:465–468

    PubMed  CAS  Google Scholar 

  • Langley SJ, Allen DJ, Houghton C, Woodcock A (2005) Efficacy of EPI-2010 (an inhaled respirable anti-sense oligonucleotide: RASON) in moderate/severe persistent asthma. Am J Resp Crit Care Med 171:A360

    Google Scholar 

  • Lappas CM, Sullivan GW, Linden J (2005) Adenosine A2A agonists in development for the treatment of inflammation. Expert Opin Investig Drugs 14:797–806

    PubMed  CAS  Google Scholar 

  • Lee MG, Kollarik M, Chuaychoo B, Undem BJ (2004) Ionotropic and metabotropic receptor mediated airway sensory nerve activation. Pulm Pharmacol Ther 17:355–360

    PubMed  CAS  Google Scholar 

  • Lennon PF, Taylor CT, Stahl GL, Colgan SP (1998) Neutrophil-derived 5′-adenosine monophosphate promotes endothelial barrier function via CD73-mediated conversion to adenosine and endothelial A2B receptor activation. J Exp Med 188:1433–1443

    PubMed  CAS  Google Scholar 

  • Liu AMF, Wong YH (2004) G16-mediated activation of nuclear factor κB by the adenosine A1 receptor involves c-Src, protein kinase C, and ERK signaling. J Biol Chem 279:53196–53204

    PubMed  CAS  Google Scholar 

  • Livingston M, Heaney LG, Ennis M (2004) Adenosine, inflammation, and asthma: a review. Inflamm Res 53:171–178

    PubMed  CAS  Google Scholar 

  • Lloyd CM, Robinson DS (2007) Allergen-induced airway remodelling. Eur Respir J 29:1020–1032

    PubMed  CAS  Google Scholar 

  • Luijk B, van den Berge M, Kerstjens HA, Postma DS, Cass L, Sabin A, Lammers JW (2008) Effect of an inhaled adenosine A2A agonist on the allergen-induced late asthmatic response. Allergy 63:75–80

    PubMed  CAS  Google Scholar 

  • Lukashev D, Ohta A, Apasov S, Chen JF, Sitkovsky M (2004) Cutting edge: physiologic attenuation of proinflammatory transcription by the Gs protein-coupled A2A adenosine receptor in vivo. J Immunol 173:21–24

    PubMed  CAS  Google Scholar 

  • Ma B, Blackburn MR, Lee CG, Homer RJ, Liu W, Flavell RA, Boyden L, Lifton RP, Sun C-X, Young HW, Elias JA (2006) Adenosine metabolism and murine strain-specific IL-4-induced inflammation, emphysema, and fibrosis. J Clin Invest 116:1274–1283

    PubMed  CAS  Google Scholar 

  • Madara JL, Patapoff TW, Gillece-Castro B, Colgan SP, Parkos CA, Delp C, Mrsny RJ (1993) 5′-Adenosine monophosphate is the neutrophil-derived paracrine factor that elicits chloride secretion from T84 intestinal epithelial cell monolayers. J Clin Invest 91:2320–2325

    PubMed  CAS  Google Scholar 

  • Mann JS, Cushley MJ, Holgate ST (1985) Adenosine-induced bronchoconstriction in asthma. Role of parasympathetic stimulation and adrenergic inhibition. Am Rev Respir Dis 132:1–6

    CAS  Google Scholar 

  • Mann JS, Holgate ST, Renwick AG, Cushley MJ (1986a) Airway effects of purine nucleosides and nucleotides and release with bronchial provocation in asthma. J Appl Physiol 61:1667–1676

    PubMed  CAS  Google Scholar 

  • Mann JS, Renwick AG, Holgate ST (1986b) Release of adenosine and its metabolites from activated human leucocytes. Clin Sci 70:461–468

    PubMed  CAS  Google Scholar 

  • Manrique HA, Gómez FP, Muñoz PA, Peña AM, Barberà JA, Roca J, Rodríguez-Roisin R (2008) Adenosine 5′-monophosphate in asthma: gas exchange and sputum cellular responses. Eur Respir J 31:1205–1212

    PubMed  CAS  Google Scholar 

  • Marcus AJ, Safier LB, Broekman MJ, Islam N, Fliessbach JH, Hajjar KA, Kaminski WE, Jendraschak E, Silverstein RL, von Schacky C (1995) Thrombosis and inflammation as multicellular processes: significance of cell–cell interactions. Thromb Haemost 74: 213–217

    PubMed  CAS  Google Scholar 

  • McNamara N, Gallup M, Khong A, Sucher A, Maltseva I, Fahy J, Basbaum C (2004) Adenosine up-regulation of the mucin gene, MUC2, in asthma. FASEB J 18:1770–1772

    PubMed  CAS  Google Scholar 

  • Mohsenin A, Mi T, Xia Y, Kellems RE, Chen JF, Blackburn MR (2007) 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 293:L753–L761

    PubMed  CAS  Google Scholar 

  • Montesinos MC, Gadangi P, Longaker M, Sung J, Levine J, Nilsen D, Reibman J, Li M, Jiang C-K, Hirschhorn R, Recht PA, Ostad E, Levin RI, Cronstein BN (1997) Wound healing is accelerated by agonists of adenosine A2 (Gs-linked) receptors. J Exp Med 186:1615–1620

    PubMed  CAS  Google Scholar 

  • Montesinos MC, Shaw JP, Yee H, Shamamian P, Cronstein BN (2006) Adenosine A(2A) receptor activation promotes wound neovascularization by stimulating angiogenesis and vasculogenesis. Am J Pathol 164:1887–1892

    Google Scholar 

  • Moro S, Gao Z-G, Jacobson KA, Spalluto G (2006) Progress in the pursuit of therapeutic adenosine receptor antagonists. Med Res Rev 26:131–159

    PubMed  CAS  Google Scholar 

  • Mustafa SJ, Nadeem A, Fan M, Zhong H, Belardinelli L, Zeng D (2007) Effect of a specific and selective A(2B) adenosine receptor antagonist on adenosine agonist AMP and allergen-induced airway responsiveness and cellular influx in a mouse model of asthma. J Pharmacol Exp Ther 320:1246–1251

    PubMed  CAS  Google Scholar 

  • Nadeem A, Obiefuna PC, Wilson CN, Mustafa SJ (2006) Adenosine A1 receptor antagonist versus montelukast on airway reactivity and inflammation. Eur J Pharmacol 551:116–124

    PubMed  CAS  Google Scholar 

  • Nadeem A, Fan M, Ansari HR, Ledent C, Jamal Mustafa S (2007) Enhanced airway reactivity and inflammation in A2A adenosine receptor-deficient allergic mice. Am J Physiol Lung Cell Mol Physiol 292:L1335–L1344

    PubMed  CAS  Google Scholar 

  • Nadeem A, Ponnoth DS, Batchelor T, Dey RD, Ledent C, Mustafa SJ (2008) Decreased tracheal relaxation via NADPH oxidase activation in A2A AR deficent allergic mice. Am J Respir Crit Care Med 177:A487

    Google Scholar 

  • Nilsson G, Blom T, Kusche-Gullberg M, Kjellen L, Butterfield JH, Sundstrom C, Nilsson K, Hellman L (1994) Phenotypic characterization of the human mast cell line HMC-1. Scand J Immunol 39:489–498

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Obiefuna PC, Batra VK, Nadeem A, Borron P, Wilson CN, Mustafa SJ (2005) A novel A1 adenosine receptor antagonist, L-97-1 [3-[2-(4-aminophenyl)-ethyl]-8-benzyl-7-{2-ethyl-(2-hydroxy-ethyl)-amino]-ethyl}-1-propyl-3,7-dihydro-purine-2,6-dione], reduces allergic responses to house dust mite in an allergic rabbit model of asthma. J Pharmacol Exp Ther 315:329–336

    PubMed  CAS  Google Scholar 

  • O’Connor BJ, Crowther SD, Costello JF, Morley J (1999) Selective airway responsiveness in asthma. Trends Pharmacol Sci 20:9–11

    PubMed  Google Scholar 

  • Ohta A, Gorelik E, Prasad SJ, Ronchese F, Lukashev D, Wong MK, Huang X, Caldwell S, Liu K, Smith P, Chen JF, Jackson EK, Apasov S, Abrams S, Sitkovsky M (2006) A2A adenosine receptor protects tumors from antitumor T cells. Proc Natl Acad Sci USA 103:13132–13137

    PubMed  CAS  Google Scholar 

  • Oldenburg PJ, Mustafa SJ (2005) Involvement of mast cells in adenosine-mediated bronchoconstriction and inflammation in an allergic mouse model. J Pharmacol Exp Ther 313:319–324

    PubMed  CAS  Google Scholar 

  • Panther E, Idzko M, Herouy Y, Rheinen H, Gebicke-Haerter PJ, Mrowietz U, Dichmann S, Norgauer J (2001) Expression and function of adenosine receptors in human dendritic cells. FASEB J 15:1963–1970

    PubMed  CAS  Google Scholar 

  • Pascoe SJ, Knight H, Woessner R (2007) QAF805, an A2b/A3 adenosine receptor antagonist does not attenuate AMP challenge in subjects with asthma. Am J Respir Crit Care Med 175:A682

    Google Scholar 

  • Pastor-Anglada M, Casado FJ, Valdes R, Mata J, Garcia-Manteiga J, Molina M (2001) Complex regulation of nucleoside transporter expression in epithelial and immune system cells. Mol Membr Biol 18:81–85

    PubMed  CAS  Google Scholar 

  • Phillips GD, Holgate ST (1989) The effect of oral terfenadine alone and in combination with flurbiprofen on the bronchoconstrictor response to inhaled adenosine 5′-monophosphate in nonatopic asthma. Am Rev Respir Dis 139:463–469

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Polosa R, Phillips GD, Rajakulasingam K, Holgate ST (1991) The effect of inhaled ipratropium bromide alone and in combination with oral terfenadine on bronchoconstriction provoked by adenosine 5′-monophosphate and histamine in asthma. J Allergy Clin Immunol 87:939–947

    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 151:624–629

    PubMed  CAS  Google Scholar 

  • Polosa R, Renaud L, Cacciola R, Prosperini G, Crimi N, Djukanovic R (1998) Sputum eosinophilia is more closely associated with airway responsiveness to bradykinin than methacholine in asthma. Eur Respir J 12:551–556

    PubMed  CAS  Google Scholar 

  • Press NJ, Taylor RJ, Fullerton JD, Tranter P, McCarthy C, Keller TH, Brown L, Cheung R, Christie J, Haberthuer S, Hatto JD, Keenan M, Mercer MK, Press NE, Sahri H, Tuffnell AR, Tweed M, Fozard JR (2005) A new orally bioavailable dual adenosine A2B/A3 receptor antagonist with therapeutic potential. Bioorg Med Chem Lett 15:3081–3085

    PubMed  CAS  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 268:16887–16890

    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 49:666–672

    PubMed  CAS  Google Scholar 

  • Resta R, Yamashita Y, Thompson LF (1998) Ecto-enzyme and signaling functions of lymphocyte CD73. Immunol Rev 161:95–109

    PubMed  CAS  Google Scholar 

  • Reynolds CJ, Togias A, Proud D (2002) Airways hyper-responsiveness to bradykinin and methacholine: effects of inhaled fluticasone. Clin Exp Allergy 32:1174–1179

    PubMed  CAS  Google Scholar 

  • Reynolds SM, Docherty R, Robbins J, Spina D, Page CP (2008) Adenosine induces a cholinergic tracheal reflex contraction in guinea pigs in vivo via an adenosine A1 receptor-dependent mechanism. J Appl Physiol 105:187–196

    PubMed  CAS  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 37:8–14

    PubMed  CAS  Google Scholar 

  • Roisman GL, Lacronique JG, Desmazes DN, Carre C, Le-Cae A, Dusser DJ (1996) Airway responsiveness to bradykinin is related to eosinophilic inflammation in asthma. Am J Respir Crit Care Med 153:381–390

    PubMed  CAS  Google Scholar 

  • Roman J, Rivera HN, Roser-Page S, Sitaraman SV, Ritzenthaler JD (2006) Adenosine induces fibronectin expression in lung epithelial cells: implications for airway remodeling. Am J Physiol Lung Cell Mol Physiol 290:L317–L325

    PubMed  CAS  Google Scholar 

  • Rorke S, Holgate ST (2002) Targeting adenosine receptors: novel therapeutic targets in asthma and chronic obstructive pulmonary disease. Am J Respir Med 1:99–105

    PubMed  CAS  Google Scholar 

  • Rorke S, Jennison S, Jeffs JA, Sampson AP, Holgate ST (2002) Role of cysteinyl leukotrienes in adenosine 5′-monophosphate induced bronchoconstriction in asthma. Thorax 57:323–327

    PubMed  CAS  Google Scholar 

  • Rosenberg HF, Phipps S, Foster PS (2007) Eosinophil trafficking in allergy and asthma. J Allergy Clin Immunol 119:1303–1310

    PubMed  CAS  Google Scholar 

  • Rounds S, Hsieh L, Agarwal KC (1994) Effects of endotoxin injury on endothelial cell adenosine metabolism. J Lab Clin Med 123:309–317

    PubMed  CAS  Google Scholar 

  • Rutgers SR, Koeter GH, Van Der Mark TW, Postma DS (1999) Protective effect of oral terfenadine and not inhaled ipratropium on adenosine 5′-monophosphate-induced bronchoconstriction in patients with COPD. Clin Exp Allergy 29:1287–1292

    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: 7726–7733

    PubMed  CAS  Google Scholar 

  • Ryzhov S, Zaynagetdinov R, Goldstein AE, Novitskiy SV, Dikov MM, Blackburn MR, Biaggioni I, Feoktistov I (2008a) Effect of A2B adenosine receptor gene ablation on proinflammatory adenosine signaling in mast cells. J Immunol 180:7212–7220

    PubMed  CAS  Google Scholar 

  • Ryzhov S, Zaynagetdinov R, Goldstein AE, Novitskiy SV, Blackburn MR, Biaggioni I, Feoktistov I (2008b) Effect of A2B adenosine receptor gene ablation on adenosine-dependent regulation of proinflammatory cytokines. J Pharmacol Exp Ther 324:694–700

    PubMed  CAS  Google Scholar 

  • Salmon JE and Cronstein BN (1990) Fc gamma receptor-mediated functions in neutrophils are modulated by adenosine receptor occupancy. A1 receptors are stimulatory and A2 receptors are inhibitory. J Immunol 145: 2235–2240

    PubMed  CAS  Google Scholar 

  • Salmon JE, Brogle N, Brownlie C, Edberg JC, Kimberly RP, Chen BX, Erlanger BF (1993) Human mononuclear phagocytes express adenosine A1 receptors. A novel mechanism for differential regulation of Fc gamma receptor function. J Immunol 151:2775–2785

    CAS  Google Scholar 

  • Salpeter SR, Ormiston TM, Salpeter EE (2004) Cardiovascular effects of beta-agonists in patients with asthma and COPD: a metanalysis. Chest 125:2309–2321

    PubMed  CAS  Google Scholar 

  • Slats AM, Janssen K, van SA, van der Plas DT, Schot R, van den Aardweg JG, de Jongste JC, Hiemstra PS, Mauad T, Rabe KF, Sterk PJ (2007) Bronchial inflammation and airway responses to deep inspiration in asthma and chronic obstructive pulmonary disease. Am J Respir Crit Care Med 176:121–128

    PubMed  Google Scholar 

  • Sont JK, Booms P, Bel EH, Vandenbroucke JP, Sterk PJ (1993) The determinants of airway hyperresponsiveness to hypertonic saline in atopic asthma in vivo. Relationship with sub-populations of peripheral blood leucocytes. Clin Exp Allergy 23:678–688

    CAS  Google Scholar 

  • Sperlagh B, Hasko G, Nemeth Z, Vizi ES (1998) ATP released by LPS increases nitric oxide production in raw 264.7 macrophage cell line via P2Z/P2X7 receptors. Neurochem Int 33: 209–215

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Spicuzza L, Di Maria G, Polosa R (2006) Adenosine in the airways: implications and applications. Eur J Pharmacol 533:77–88

    PubMed  CAS  Google Scholar 

  • Spina D, Page CP (1996) Airway sensory nerves in asthma: targets for therapy? Pulm Pharmacol 9:1–18

    PubMed  CAS  Google Scholar 

  • Spina D, Page CP (2002) Pharmacology of airway irritability. Curr Opin Pharmacol 2:264–272

    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 31:943–951

    PubMed  CAS  Google Scholar 

  • Sullivan GW (2003) Adenosine A2A receptor agonists as anti-inflammatory agents. Curr Opin Investig Drugs 4:1313–1319

    PubMed  CAS  Google Scholar 

  • Sun CX, Young HW, Molina JG, Volmer JB, Schnermann J, Blackburn MR (2005) A protective role for the A1 adenosine receptor in adenosine-dependent pulmonary injury. J Clin Invest 115:35–43

    PubMed  CAS  Google Scholar 

  • Sun CX, Zhong H, Mohsenin A, Morschl E, Chunn JL, Molina JG, Belardinelli L, Zeng D, Blackburn MR (2006) Role of A2B adenosine receptor signaling in adenosine-dependent pulmonary inflammation and injury. J Clin Invest 116:2173–2182

    PubMed  CAS  Google Scholar 

  • Thiel M, Caldwell CC, Sitkovsky MV (2003) The critical role of adenosine A2A receptors in downregulation of inflammation and immunity in the pathogenesis of infectious diseases. Microb Infect 5:515–526

    CAS  Google Scholar 

  • Thompson LF, Eltzschig HK, Ibla JC, Van De Wiele CJ, Resta R, Morote-Garcia JC, Colgan SP (2004) Crucial role for ecto-5′-nucleotidase (CD73) in vascular leakage during hypoxia. J Exp Med 200:1395–1405

    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 171:331–337

    PubMed  CAS  Google Scholar 

  • van den Berge M, Kerstjens HA, Meijer RJ, de Reus DM, Koeter GH, Kauffman HF, Postma DS (2001) Corticosteroid-induced improvement in the PC20 of adenosine monophosphate is more closely associated with reduction in airway inflammation than improvement in the PC20 of methacholine. Am J Respir Crit Care Med 164:1127–1132

    PubMed  Google Scholar 

  • van den Berge M, Kerstjens HA, de Reus DM, Koeter GH, Kauffman HF, Postma DS (2004) Provocation with adenosine 5′-monophosphate, but not methacholine, induces sputum eosinophilia. Clin Exp Allergy 34:71–76

    PubMed  Google Scholar 

  • Van Schoor J, Joos GF, Pauwels RA (2000) Indirect bronchial hyperresponsiveness in asthma: mechanisms, pharmacology and implications for clinical research. Eur Respir J 16:514–533

    PubMed  Google Scholar 

  • Van Schoor J, Joos GF, Pauwels RA (2002) Effect of inhaled fluticasone on bronchial responsiveness to neurokinin A in asthma. Eur Respir J 19:997–1002

    PubMed  Google Scholar 

  • van Troostenburg A-R, Clark EV, Carey WDH, Warrington SJ, Kerns WD, Cohn I, Silverman MH, Bar-Yehuda S, Fong K-LL, Fishman P (2004) Tolerability, pharmacokinetics and concentration-dependent hemodynamic effects of oral CF 101, an A3 adenosine receptor agonist, in healthy young men. Internat J Clin Pharmacol Ther 42:534–542

    Google Scholar 

  • Visser SS, Theron AJ, Ramafi G, Ker JA, Anderson R (2000) Apparent involvement of the A2A subtype adenosine receptor in the anti-inflammatory interactions of CGS 21680, cyclopentyladenosine, and IB-MECA with human neutrophils. Biochem Pharmacol 60:993–999

    PubMed  CAS  Google Scholar 

  • Vizi E, Huzzar E, Csoma Z, Boszormenyi-Nagy G, Barat E, Horvath I, Herjavecz I, Kollai M (2002) Plasma adenosine concentration increases during exercise: a possible contributing factor in exercise-induced bronchoconstriction in asthma. J Allergy Clin Immunol 109:446–448

    PubMed  CAS  Google Scholar 

  • Walker BAM, 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 16:531–537

    PubMed  CAS  Google Scholar 

  • Webb RL, Sills MA, Chovan JP, Peppard JV, Francis JE (1993) Development of tolerance to the antihypertensive effects of highly selective adenosine A2a agonists upon chronic administration. J Pharmacol Exp Ther 267:287–295

    PubMed  CAS  Google Scholar 

  • Wilson CN, Batra VK (2002) Lipopolysaccharide binds to and activates A(1) adenosine receptors on human pulmonary artery endothelial cells. J Endotoxin Res 8:263–271

    PubMed  CAS  Google Scholar 

  • Wilson CN (2008) Adenosine receptors and asthma in humans. Br J Pharmacol 155:475–486

    PubMed  CAS  Google Scholar 

  • Xiang Z, Ahmed AA, Moller C, Nakayama K, Hatakeyama S, Nilsson G (2001) Essential role of the prosurvival bcl-2 homologue A1 in the mast cell survival after allergic activation. J Exp Med 194:1561–1569

    PubMed  CAS  Google Scholar 

  • Yang D, Zhang Y, Nguyen HG, Koupenova M, Chauhan AK, Makitalo M, Jones MR, Hilaire CS, Seldin DC, Toselli P, Lamperti E, Schreiber BM, Gavras H, Wagner DD, Ravid K (2006) The A(2B) adenosine receptor protects against inflammation and excessive vascular adhesion. J Clin Invest 116:1913–1923

    PubMed  CAS  Google Scholar 

  • Yang D, Koupenova M, McCrann DJ, Kopeikina KJ, Kagan HM, Schreiber BM, Ravid K (2008) The A2b adenosine receptor protects against vascular injury. Proc Natl Acad Sci USA 105: 792–796

    PubMed  CAS  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 173:1380–1389

    PubMed  CAS  Google Scholar 

  • Young HW, Sun CX, Evans CM, Dickey BF, Blackburn MR (2006) A3 adenosine receptor signaling contributes to airway mucin secretion after allergen challenge. Am J Respir Cell Mol Biol 35:549–558

    PubMed  CAS  Google Scholar 

  • Yuzlenko O, Kiec-Kononowicz K (2006) Potent adenosine A1 and A2A receptor antagonists: recent developments. Curr Med Chem 13:3609–3625

    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 171:338–345

    PubMed  CAS  Google Scholar 

  • Zhong H, Belardinelli L, Maa T, Feoktistov I, Biaggioni I, Zeng D (2004) A2B adenosine receptors increase cytokine release by bronchial smooth muscle cells. Am J Respir Cell Mol Biol 30: 118–125

    PubMed  CAS  Google Scholar 

  • Zhong H, Belardinelli L, Maa T, Zeng D (2005) Synergy between A2B adenosine receptors and hypoxia in activating human lung fibroblasts. Am J Respir Cell Mol Biol 32:2–8

    PubMed  CAS  Google Scholar 

  • Zhong H, Wu Y, Belardinelli L, Zeng D (2006) A2B adenosine receptors induce IL-19 from bronchial epithelial cells and results in TNF-alpha increase. Am J Respir Cell Mol Biol 35: 587–592

    PubMed  CAS  Google Scholar 

  • Zimmermann H (1999) Nucleotides and cd39: principal modulatory players in hemostasis and thrombosis. Nat Med 5:987–988

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank would like to Michael R. Blackburn, Ph.D. (Professor, Department of Biochemistry and Molecular Biology, The University of Texas–Houston Medical School, Houston, TX, USA) for his critical review of this chapter and his helpful comments.

Author information

Authors and Affiliations

  1. Endacea, Inc., P.O. Box 12076 (Mail), 2 Davis Drive (Courier), Research Triangle Park, NC, 27709-2076, USA

    Constance N. Wilson

  2. Department of Physiology and Pharmacology, School of Medicine, West Virginia University, Morgantown, WV, 26505-9229, USA

    Ahmed Nadeem

  3. Sackler Institute of Pulmonary Pharmacology, Division of Pharmaceutical Science, School of Biomedical and Health Science, King’s College London, London, SE1 1UL, UK

    Domenico Spina

  4. Sackler Institute of Pulmonary Pharmacology, Division of Pharmaceutical Science, School of Biomedical and Health Science, King’s College London, London, SE1 1UL, UK

    Rachel Brown

  5. Sackler Institute of Pulmonary Pharmacology, Division of Pharmaceutical Science, School of Biomedical and Health Science, King’s College London, London, SE1 1UL, UK

    Clive P. Page

  6. Department of Physiology and Pharmacology, School of Medicine, West Virginia University, Morgantown, WV, 26505-9229, USA

    S. Jamal Mustafa

Authors
  1. Constance N. Wilson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ahmed Nadeem
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Domenico Spina
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rachel Brown
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Clive P. Page
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S. Jamal Mustafa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Constance N. Wilson .

Editor information

Editors and Affiliations

  1. Endacea, Inc.,, Davis Drive 2, Research Triangle Park, 27709-2076, U.S.A.

    Constance N. Wilson

  2. Health Sciences Center, West Virginia University, Health Sciences S. 2267, Morgantown, 26506-9104, U.S.A.

    S. Jamal Mustafa

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Wilson, C.N., Nadeem, A., Spina, D., Brown, R., Page, C.P., Mustafa, S.J. (2009). Adenosine Receptors and Asthma. In: Wilson, C., Mustafa, S. (eds) Adenosine Receptors in Health and Disease. Handbook of Experimental Pharmacology, vol 193. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-89615-9_11

Download citation

Publish with us

Policies and ethics

Search

Navigation