Skip to main content
NCBI home page
Indian Journal of Clinical Biochemistry logoLink to Indian Journal of Clinical Biochemistry
. 2001 Jul;16(2):140–144. doi: 10.1007/BF02864852

Adenosine and its role in asthma

Shrinivas B Rao 1,✉
PMCID: PMC3453636  PMID: 23105309

Abstract

Endogenous adenosine formed from ADP and AMP by the action of ATPase and 5′-nucleotidase is known to cause bronchoconstriction and asthma in humans. It has been suggested that this action of adenosine is due to its binding to specific purino receptors in the mast cells in the lungs and consequent release of mediators which elicit bronchoconstriction and asthma. The release of these mediators leading to asthma was also believed to be due to vagal stimulation by adenosine. Though the role of adenosine in causing bronchoconstriction leading to asthma is well confirmed the actual mode of action and details of the mechanisms involved in the clinical manifestation of asthma remain unclear.

Keywords: Adenosine, Asthma, Bronchoconstriction, Allergy, Mast Cells

Full Text

The Full Text of this article is available as a PDF (411.0 KB).

References

  • 1.Rao S.B., Mehendale H.M. Uptake and disposition of putrescine, spermidine and spermine by rabbit lungs. Drug Metab. Disposi. 1987;15:189–194. [PubMed] [Google Scholar]
  • 2.Rao S.B., Mehendale H.M. Passive sequastration of putrescine spermidine and spermine by rat lungs. Biochem. Biophys. Acta. 1988;966:22–30. doi: 10.1016/0304-4165(88)90124-9. [DOI] [PubMed] [Google Scholar]
  • 3.Phillips, G.D. and Holgate, S.T. (1988) The mechanism of adenosine- induced brochoconstriction in asthma ISI Atlas of Sci. Pharmacol. 28–32.
  • 4.Fain J.N., Malbon C.C. Regulation of adenylate cyclase by adenosine. Mol. Cell. Biochem. 1979;25:143–169. doi: 10.1007/BF00235364. [DOI] [PubMed] [Google Scholar]
  • 5.Marquart D.L., Parker C.E., Sullivan T.J. Potentiation of mast cell mediator release by adenosine. J.Immunol. 1978;120:871–878. [PubMed] [Google Scholar]
  • 6.Cushley M.K., Tattersfield A.E., Holgate S.T. Inhaled adenosine and guanosine on airway resistance in nomal and asthmatic subjects. Brit.J.Clin.Pharmacol. 1983;15:161–165. doi: 10.1111/j.1365-2125.1983.tb01481.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Fowler S.J., Dempsey O.J., Sims E.J., Lipworth B.J. Screening for bronchial hyperresponsiveness using methacholine and AMP. Relationship to asthma severity and beta (2) receptor genotype. Amer. J. Resp. Crit. Care. 2000;162:1318–1322. doi: 10.1164/ajrccm.162.4.9912103. [DOI] [PubMed] [Google Scholar]
  • 8.Avital A., Godfrey S., Springer C. Exercise, methacholine and AMP challenges in children with asthma: relation to severity of the disease. Peaditr. Pulmonol. 2000;30:207–214. doi: 10.1002/1099-0496(200009)30:3<207::AID-PPUL5>3.0.CO;2-Z. [DOI] [PubMed] [Google Scholar]
  • 9.Jokic R., Swystun V.A., Davis B.E., Cockcrof D.W. Regular inhaled salbutamol: effect on airway responsiveness to methacholine and AMP and tolerence to bronchoprotection. Chest. 2001;119:370–375. doi: 10.1378/chest.119.2.370. [DOI] [PubMed] [Google Scholar]
  • 10.Holgate S.T., Arshad H., Stryszak P., Harrison J.E. Mometasone furoate antagonizes AMP induced bronchoconstriction in patients with mild asthma. J.Allergy Clin. Immunol. 2000;105:906–911. doi: 10.1067/mai.2000.105709. [DOI] [PubMed] [Google Scholar]
  • 11.Rutgers S.R., Koeter G.H., Vander Mark T.W., Postma D.S. Protective effect of oral terfenadine and not inhaled ipratropium on AMP induced bronchoconstriction in patients with COPD. Clin. Exp. Allergy. 1999;29:1287–1292. doi: 10.1046/j.1365-2222.1999.00650.x. [DOI] [PubMed] [Google Scholar]
  • 12.Nightingale J.A., Rogers D.F., Barnes P.J. Differential effect of formoterol om AMP and histamine reactivity in asthma. Amer. J. Resp. Crit. Care Med. 1999;159:1786–1790. doi: 10.1164/ajrccm.159.6.9809090. [DOI] [PubMed] [Google Scholar]
  • 13.Church M.K., Holgate S.T. Adenosine and asthma. Trends in Pharmacol. Sci. 1986;7:49–50. doi: 10.1016/0165-6147(86)90248-8. [DOI] [Google Scholar]
  • 14.Mentzer R.M., Rubio R., Beme R.M. Release of adenosine from hypoxic canine lung tissue and its possible role in the pulmonary circulation. Amer. J.Physiol. 1975;229:1625–1631. doi: 10.1152/ajplegacy.1975.229.6.1625. [DOI] [PubMed] [Google Scholar]
  • 15.Ng W.H., Polosa R., Church M.K. Adenosine brochoconstriction in asthma: investigation into its possible mechanism of action. Brit. J. Clin. Pharmacol. 1990;30:898–905. doi: 10.1111/j.1365-2125.1990.tb05474.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Avital A., Springer C., Bar-Yishay E., Godfrey S. Adenosine, methacholine and exercise challenges in children with asthma or paediatric chronic obstructive pulmonary disease. Thorax. 1995;50:511–516. doi: 10.1136/thx.50.5.511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Mann J.S., Holgate S.T., Renwick A.G., Cushley M.J. Airway effects of purine nucleosides and nuclotides and release with bronchial provocation in asthma. J. Appl. Physiol. 1986;61:1667–1676. doi: 10.1152/jappl.1986.61.5.1667. [DOI] [PubMed] [Google Scholar]
  • 18.Beme R.M. In Purines: Pharmacol.and Physiological roles Ed. Stone. London: T.W.Mac Millan; 1985. pp. 125–130. [Google Scholar]
  • 19.Phillips G.D., Refferty P., Beasley C.R.W., Holgate S.T. The effect of oral terfenadine on the brochoconstrictor response to inhaled histamine and AMP in non-atopic asthma. Thorax. 1987;42:939–945. doi: 10.1136/thx.42.12.939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Cushley M.J., Tattersfield A.E., Holgate S.T. Adenosine induced brochoconstriction in asthma: antagonism by inhaled theophylline. Amer. Rev. Respir. Dis. 1984;129:380–384. doi: 10.1164/arrd.1984.129.3.380. [DOI] [PubMed] [Google Scholar]
  • 21.Cushley M.J., Tallant N., Holgate S.T. The effect of single dose intravenous dipyridamole on histamine and adenosine induced brochoconstriction in normal and asthmatic subjects. Eur. J. Respir. Dis. 1986;86:185–192. [PubMed] [Google Scholar]
  • 22.Pauwels R.A., Joos G.F. Charaterization of the adenosine receptors in the airways. Arch. Int.Pharmocodyn.Therp. 1995;329:151–160. [PubMed] [Google Scholar]
  • 23.Feoktistov I., Biaggioni I. Adenosine A2b receptor. Pharmacol. Rev. 1997;49:381–402. [PubMed] [Google Scholar]
  • 24.Linden J., Auchampach J.A., Jin X., Figler R.A. The structure and function of A1 and A2b receptors. Life Sci. 1998;62:1519–1524. doi: 10.1016/S0024-3205(98)00100-3. [DOI] [PubMed] [Google Scholar]
  • 25.Jacobson K.A. Adenosine A3 receptors: novel ligands and paradoxical effects. Trends Pharmacol. Sci. 1998;19:184–191. doi: 10.1016/S0165-6147(98)01203-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Fozard J.R., Hannon J.P. Adenosine receptor ligands: potential as therapeutic agents in asthma and COPD. Pulm. Pharmacol. Ther. 1999;12:111–114. doi: 10.1006/pupt.1999.0191. [DOI] [PubMed] [Google Scholar]
  • 27.Feoktistov I., Polosa R., Holgate S.T., Biaggioni I. Adenosine A2b receptors: a novel therapeutic target in asthma. Trends Pharmacol. Sci. 1998;19:148–153. doi: 10.1016/S0165-6147(98)01179-1. [DOI] [PubMed] [Google Scholar]
  • 28.Polosa R., Crimi N., Vancheri C., Holgate S.T., Church M.K., Mistretta A. Release of Mast cell derived mediators after endobronchial adenosine challenge in asthma. Amer. J. Respir. Crit. Care Med. 1995;151:624–629. doi: 10.1164/ajrccm/151.3_Pt_1.624. [DOI] [PubMed] [Google Scholar]
  • 29.Forsythe P., Ennis M. Adenosine, mast cell and asthma. Inflamm. Res. 1999;48:301–307. doi: 10.1007/s000110050464. [DOI] [PubMed] [Google Scholar]
  • 30.Cushley M.J., Holgate S.T. Adenosine induced brochoconstriction in asthma: Role of mast cell mediator release. J. Allergy Clin. Immunol. 1985;75:272–278. doi: 10.1016/0091-6749(85)90057-0. [DOI] [PubMed] [Google Scholar]
  • 31.Howarth P.H., Durham S.R., Lee T.H., Kay A.B., Holgate S.T. Influence of albuterol, cromolyn sodium and ipratropium bromide on the airway and circulating mediator responses to antigen bronchial provocation in asthma. Amer. Rev. Respir. Dis. 1985;132:986–992. doi: 10.1164/arrd.1985.132.5.986. [DOI] [PubMed] [Google Scholar]
  • 32.Feoktistov I., Biaggion I. Adenosine A2b receptors evoke interleukin-8 secretion in human mast cells: An enprofylline sensitive mechanism with implications for asthm. J. Clin. Invest. 1995;96:1979–1986. doi: 10.1172/JCI118245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Coward W.R., Sagara H., Church M.K. Asthma, adenosine, mast cells and theophylline. Clin. Exp. Allergy. 1998;28:42–46. [PubMed] [Google Scholar]
  • 34.Marquardt D.L. Mast cell adenosine receptor characteristics and signalling. Adv. Exp. Med. Biol. 1998;431:79–82. doi: 10.1007/978-1-4615-5381-6_15. [DOI] [PubMed] [Google Scholar]
  • 35.O'Connor B.J., Fuller R.W., Barnes P.J. Nonbronchodilator effects of inhaled beta2 agonists:Greater protection against AMP than methacholine induced brochoconstriction in asthma. Amer. J. Respir. Crit. Care Med. 1994;150:381–387. doi: 10.1164/ajrccm.150.2.8049819. [DOI] [PubMed] [Google Scholar]
  • 36.Driver A.G., Kukoly C.A., Ali S., Mustafa S.J. Adenosine in brochoalveolar lavage fluid in asthma. Amer.Rev.Respir.Dis. 1993;148:91–97. doi: 10.1164/ajrccm/148.1.91. [DOI] [PubMed] [Google Scholar]
  • 37.Polosa R., Nig. W.H., Crimi N., Vancheri C., Holgate S.T., Church M.K., Mistretta A. Release of mast cell derived mediators after endobronchial adenosine challenge in asthma. Amer. J. Respir. Crit. Care Med. 1995;151:624–629. doi: 10.1164/ajrccm/151.3_Pt_1.624. [DOI] [PubMed] [Google Scholar]
  • 38.Forsythe P., McGarvey L.P., Heaney L.G., MacMohan J., Ennis M. Adenosine induces histamine release from human bronchoalveolar lavage mast cells. Clin. Sci. 1999;96:349–355. doi: 10.1042/CS19980228. [DOI] [PubMed] [Google Scholar]
  • 39.Crimi N., Palermo F., Oliver R., Polosa R., Settinieri I, Mistretta A. Protective effects of inhaled ipratropium bromide on brochoconstriction induced by adenosine and methacholine in asthma. Eur. Respir. J. 1992;5:560–565. [PubMed] [Google Scholar]
  • 40.Okayama M., Ma T.Y., Mataoka I. Role of vagal nerve activity on adenosine induced brochoconstriction in asthma. Amer. Rev. Respir. Dis. 1986;133:93–97. [Google Scholar]
  • 41.Pauwels R. The role of adenosine in brochial asthma. Bull. Eur. Physiopathol. Respir. 1987;23:203–208. [PubMed] [Google Scholar]
  • 42.Wang M., Wisniewski A., Pavord I., Knox A., Tattersfield A. Comparison of three inhaled non-steroidal anti-inflammatory drugs on the airways response to sodium metabisulphite and AMP challenge in asthma. Thorax. 1996;51:799–804. doi: 10.1136/thx.51.8.799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43.Bames P.J. Cyclic nucleotides and phosphodiesterases and airway function. Eur.Respir.J. 1995;8:457–462. doi: 10.1183/09031936.95.08030457. [DOI] [PubMed] [Google Scholar]
  • 44.Mundell S.J., Olah M.E., Panettieri R.A., Benovic J.L., Penn R.B. Regulation of G proteincoupled receptor-adenyl cyclase responsiveness in human air way smooth muscle by exogenous and autocrine adenosine. Amer. J. Resp. Cell. Mol. Biol. 2001;24:155–163. doi: 10.1165/ajrcmb.24.2.4243. [DOI] [PubMed] [Google Scholar]
  • 45.Ceyhan B.B., Celikel T. Effect of inhaled heparin on adenosine induced bronchial hyperreactivity. Int. J. Clin. Pharmacol. Ther. 1997;35:208–213. [PubMed] [Google Scholar]
  • 46.VanSchoor J., Joos. G.F., Drajesk J.F., Carpenter P.J., Pauwels R.A. The effect of ABT-761 a novel 5-lipoxygenase inhibitor on exercise and adenosine induced bronchoconstriction in asthmatic subjects. Amer.J.Resp.Crit.Care Med. 1997;155:875–880. doi: 10.1164/ajrccm.155.3.9117020. [DOI] [PubMed] [Google Scholar]

Articles from Indian Journal of Clinical Biochemistry are provided here courtesy of Springer

RESOURCES