Agents and Actions

, Volume 10, Issue 1–2, pp 145–147 | Cite as

Are the anti-allergic actions of theophylline due to antagonism at the adenosine receptor

  • Bertil B. Fredholm
  • Anita Sydbom
Histamine and Kinins Histamine and Immunology


Adenosine potentiated anaphylactic histamine release from isolated rat mast cells in a dose-dependent manner between 10−8 and 10−5M. Adenosine was found to be present during a normal incubation of mast cells, but the concentration was low (2×10−8M). In rat plasma the concentration was 1.5×10−7M. The effect of 10−5M adenosine was dose-dependently inhibited by theophylline. 50% inhibition was found at 3×10−5M theophylline. Cyclic nucleotide phosphodiesterase inhibition required much higher concentrations (IC50∼10−3M). It is suggested that some of the anti-allergic actions of theophylline (clinical concentration range: 10−5–10−4M) does not involve cyclic nucleotides but may be due to inhibition of the effects of endogenous adenosine.


Adenosine Mast Cell Histamine Theophylline Phosphodiesterase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. [1]
    I.H. Fox andW.N. Kelley,The Role of Adenosine and 2′-Deoxyadenosine in Mammalian Cells, Ann. Rev. Biochem.47, 655–686 (1978).CrossRefPubMedGoogle Scholar
  2. [2]
    J.R.S. Arch andE.A. Newsholme,The Control of the Metabolism and the Hormonal Role of Adenosine, Essays in Biochem.63, 82–123 (1979).Google Scholar
  3. [3]
    B.B. Fredholm,Local Regulation of Lipolysis in Adipose Tissue by Fatty Acids, Prostaglandins and Adenosine, Med. Biol.56, 249–261 (1978).PubMedGoogle Scholar
  4. [4]
    K.M. Piafsky andR.I. Oglivie,Dosage of Theophylline in Bronchial Asthma, N. Engl. J. Med.293, 1218–1222 (1975).Google Scholar
  5. [5]
    R.W. Butcher andE.W. Sutherland,Adenosine 3′,5′-Phosphate in Biological Materials. I. Purification and Properties of Cyclic 3′-5′-Nucleotide Phosphodisterase and Use of This Enzyme to Characterize Adenosine 3′,5′-Phosphate in Human Urine, J. biol. Chem.237, 1244–1250 (1962).PubMedGoogle Scholar
  6. [6]
    B.B. Fredholm, I. Guschin, K. Elwin, G. Schwab andB. Uvnäs,Cyclic AMP Independent Inhibition by Papaverine of Histamine Release Induced by Compound 48/80, Biochem. Pharmac.25, 1583–1588 (1976).CrossRefGoogle Scholar
  7. [7]
    B.B. Fredholm, P. Hedqvist andL. Vernet,Effect of Theophylline and Other Drugs on Rabbit Renal Phosphodiesterase, 5′-Nucleotidase and Adenosine Deaminase, Biochem. Pharmac.27, 2845–2850 (1978).CrossRefGoogle Scholar
  8. [8]
    B.B. Fredholm, K. Brodin andK. Standberg,On the Mechanism of Relaxation of Tracheal Muscle by Theophylline and Other Cyclic Nucleotide Phosphodiesterase Inhibitors, Acta pharm. tox.45, 336–344 (1979).Google Scholar
  9. [9]
    A. Sydbom andT. Karlsson,Relationship Between Serum IgE Level and Anaphylactic Histamine Release from Isolated Rat Mast Cells, Acta physiol. scand.107, 313–318 (1979).PubMedGoogle Scholar
  10. [10]
    A. Sydbom, B.B. Fredholm andB. Uvnäs,Effect of Sensitization on Spontaneous and Phosphatidyl-Serine-Induced Histamine Release and on Cyclic AMP and GMP Levels in Isolated Rat Mast Cells, Acta physiol. scand.106, 473–479 (1979).PubMedGoogle Scholar
  11. [11]
    P.A. Shore, A. Burkhalter andV.H. Cohn, Jr.,A Method for the Fluorometric Assay of Histamine in Tissues, J. Pharm. Exp. Therap.127, 182–186 (1959).Google Scholar
  12. [12]
    J.F. Harper andG. Brooker,Femtomole Sensitive Radioimmunoassay for Cyclic AMP and Cyclic GMP after 2'0-Acetylation by Acetic Anhydride in Aqueous Solution, J. Cyclic Nucl. Res.1, 207–218 (1975).Google Scholar
  13. [13]
    D.L. Marquardt, C.W. Parker andT.J. Sullivan,Potentiation of Mast Cell Mediator Release by Adenosine, J. Immunol.120, 871–878 (1978).PubMedGoogle Scholar
  14. [14]
    G.C. Mills, F.C. Schmalstieg, K.B. Trimmer, A.S. Goldman andR.M. Goldblum,Purine Metabolism in Adenosine Deaminase Deficiency, Proc. Natl. Acad. Sci.73, 2867–2871 (1976).PubMedGoogle Scholar
  15. [15]
    B.B. Fredholm andA. Sollevi,The Release of Endogenous Adenosine and Inosine from Canine Subcutaneous Adipose Tissue by Nerve Stimulation and Noradrenaline. To be published.Google Scholar
  16. [16]
    B.B. Fredholm, G. Sandberg andU. Ernström,Cyclic AMP in Freshly Prepared Thymocyte Suspensions. Evidence for Stimulation by Endogenous Adenosine, Biochem. Pharmac.27, 2675–2682 (1978).CrossRefGoogle Scholar
  17. [17]
    G. Sandberg, U. Ernström, K. Nordlind andB.B. Fredholm,Effect of Immunization on the Cyclic AMP Level and 3 H-Thymidine Incorporation in Cultured Lymphoid Cells. Int. Arch. Allergology56, 449–456 (1978).Google Scholar
  18. [18]
    G. Marone andL.M. Lichtenstein,Adenosine-Adenosine Deaminase Modulation of Histamine Release, J. Allergy clin Immunol.61, 131 (1978).Google Scholar

Copyright information

© Birkhäuser Verlag 1980

Authors and Affiliations

  • Bertil B. Fredholm
    • 1
  • Anita Sydbom
    • 1
  1. 1.Department of PharmacologyKarolinska InstitutetStockholmSweden

Personalised recommendations