Skip to main content
SpringerLink
Log in

Effect of prednisolone and ketotifen onβ 2-adrenoceptors in asthmatic patients receivingβ 2-bronchodilators

  • Originals
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Summary

In 13 patients with bronchial asthma, who were onβ 2-adrenergic bronchodilator therapy, the effects of prednisolone and ketotifen on lymphocyteβ 2-adrenoceptor density and -responsiveness were investigated. The mean lymphocyteβ 2-adrenoceptor density and -responsiveness was significantly lower than in healthy controls, presumably due to the long-termβ 2-adrenergic bronchodilator treatment. Both prednisolone 100 mg i.v. and ketotifen 1 mg b.d.p.o. for 6 days rapidly improved lymphocyteβ 2-adrenoceptor function. 16 h after prednisolone and about 6 days after the first dose of ketotifen lymphocyteβ 2-adrenoceptor density and-responsiveness had risen to values within the range in normal volunteers.

The improvement of lymphocyteβ 2-adrenoceptor function was accompanied by a significant increase in peak expiratory flow rate before and after inhalation of salbutamol.

It is concluded that prednisolone and ketotifen may act beneficially on the recovery ofβ 2-adrenoceptor responsiveness toβ 2-adrenergic bronchodilators in tolerant asthmatic patients.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Paterson JW, Woolcock AJ, Shenfield GM (1979) Bronchodilator drugs. Am Rev Respir Dis 120: 1149–1188

    Google Scholar 

  2. Nelson HS (1986) Adrenergic therapy of bronchial asthma. J Allergy Clin Immunol 77: 771–785

    Google Scholar 

  3. Harden TK (1983) Agonist-induced desensitization of theβ-adrenergic receptor-linked adenylate cyclase. Pharmacol Rev 35: 5–32

    Google Scholar 

  4. Stiles GL, Caron MG, Lefkowitz RJ (1984)β-Adrenergic receptors: Biochemical mechanisms of physiological regulation. Physiol Rev 64: 661–743

    Google Scholar 

  5. Jenne JW (1982) Whither beta-adrenergic tachyphylaxis? J Allergy Clin Immunol 70: 413–416

    Google Scholar 

  6. Davis C, Conolly ME (1980) Tachyphylaxis toβ-adrenoceptor agonists in human bronchial smooth muscle: studies in vitro. Br J Clin Pharmacol 10: 417–423

    Google Scholar 

  7. Avner BP, Jenne JW (1981) Desensitization of isolated human bronchial smooth muscle toβ-receptor agonists. J Allergy Clin Immunol 48: 51–57

    Google Scholar 

  8. Guillot C, Fornaris M, Badier M, Orehek J (1984) Spontaneous and provoked resistance to isoproterenol in isolated human bronchi. J Allergy Clin Immunol 74: 713–718

    Google Scholar 

  9. Motulsky HJ, Insel PA (1982) Adrenergic receptors in man. Direct identification, physiologic regulation and clinical alterations. N Engl J Med 307: 18–29

    Google Scholar 

  10. Tashkin DP, Conolly ME, Deutsch RI, Hui KKP, Littner M, Scarpace P, Abrass I (1982) Sbusensitization of beta-adrenoceptors in airways and lymphocytes of healthy and asthmatic subjects. Am Rev Respir Dis 125: 185–193

    Google Scholar 

  11. Hui KKP, Conolly ME, Tashkin DP (1982) Reversal of human lymphocyteβ-adrenoceptor desensitization by glucocorticoids. Clin Pharmacol Ther 32: 566–571

    Google Scholar 

  12. Samuelson WM, Davies AO (1984) Hydrocortisone-induced reversal of beta-adrenergic receptor uncoupling. Am Rev Respir Dis 130: 1023–1026

    Google Scholar 

  13. Brodde O-E, Brinkmann M, Schemuth R, O'Hara N, Daul A (1985) Terbutaline-induced desensitization of human lymphocyteβ 2-adrenoceptors. Accelerated restoration ofβ-adrenoceptor responsiveness by prednisone and ketotifen. J Clin Invest 76: 1096–1101

    Google Scholar 

  14. Böyum A (1968) Isolation of mononuclear cells and granulocytes from human blood. Scand J Clin Lab Invest 21 [Suppl 97]: 77–89

    Google Scholar 

  15. Gilman AG (1970) A protein binding assay for adenosine 3′, 5′-cyclic monophosphate. Proc Natl Acad Sci 67: 305–312

    Google Scholar 

  16. Scatchard G (1949) The attraction of proteins for small molecules and ions. Ann N Y Acad Sci 51: 660–672

    Google Scholar 

  17. O'Hara N, Daul AE, Fesel R, Siekmann U, Brodde O-E (1985) Different mechanisms underlying reducedβ 2-adrenoceptor responsiveness in lymphocytes from neonates and old subjects. Mech Ageing Dev 31: 115–122

    Google Scholar 

  18. Szentivanyi A (1968) The beta-adrenergic theory of the atopic abnormality in bronchial asthma. J Allergy 42: 203–232

    Google Scholar 

  19. Abrass IB, Scarpace PJ (1981) Human lymphocyte beta-adrenergic receptors are unaltered with age. J Gerontol 36: 298–301

    Google Scholar 

  20. Landmann R, Bittiger H, Bühler FR (1981) High affinity beta2-adrenergic receptors in mononuclear leukocytes: Similar density in young and old normal subjects. Life Sci 29: 1761–1771

    Google Scholar 

  21. Middeke M, Remien J, Holzgreve H (1984) The influence of sex, age, blood pressure and physical stress onβ 2-adrenoceptor density in mononuclear cells. J Hypertens 2: 261–264

    Google Scholar 

  22. Brodde O-E, Kretsch R, Ikezono K, Zerkowski H-R, Reidemeister J Chr (1986) Humanβ-adrenoceptors: Relation of myocardial and lymphocyteβ-adrenoceptor density. Science 231: 1584–1585

    Google Scholar 

  23. Brodde O-E (1987) Cardiac beta-adrenergic receptors. ISI Atlas Sci: Pharmacology 1: 107–112

    Google Scholar 

  24. Michel MC, Beckeringh JJ, Ikezono K, Kretsch R, Brodde O-E (1986) Lymphocyte beta2-adrenoceptors mirror precisely beta2-adrenoceptor, but poorly beta1-adrenoceptor changes in the human heart. J Hypertens 4 [Suppl 6]: S215-S218

    Google Scholar 

  25. Committee on drugs. The American Academy of Allergy and Immunology (Chairman: Sly RM) (1985) Adverse effects and complications of treatment with beta-adrenergic agonist drugs. J Allergy Clin Immunol 75: 443–449

    Google Scholar 

  26. Martinsson A, Larsson K, Hjemdahl P (1987) Studies in vivo and in vitro of terbutaline-inducedβ-adrenoceptor desensitization in healthy subjects. Clin Sci 72: 47–54

    Google Scholar 

  27. Beckeringh JJ, Brodde O-E, Daul A, Michel MC, Wang XL (1987) Haemodynamic and lymphocyteβ 2-adrenoceptor changes during procaterol treatment in man. Br J Pharmacol 90 [Suppl]: 43 P (abstract)

  28. Goldie RG, Spina D, Henry PJ, Lulich KM, Paterson JW (1986) In vitro responsiveness of human asthmatic bronchus to carbachol, histamine,β-adrenoceptor agonists and theophylline. Br J Clin Pharmacol 22: 669–676

    Google Scholar 

  29. Bretz U, Martin U, Mazzoni L, Ney UM (1983)β-Adrenergic tachyphylaxis in the rat and its reversal and prevention by ketotifen. Eur J Pharmacol 86: 321–328

    Google Scholar 

  30. Tinkelman DG, Moss BA, Bukantz SC, Sheffer AL, Dobken JH, Chodosh S, Cohen BM, Rosenthal RR, Rappaport I, Buckley CE, Chusid EL, Deutsch AJ, Settipane GA, Burns RBP (1985) A multicenter trial of the prophylactic effect of ketotifen, theophylline, and placebo in atopic asthma. J Allergy Clin Immunol 76: 487–497

    Google Scholar 

  31. Dyson AJ, Mackay AD (1980) Ketotifen in adult asthma. Br Med J 280: 360–361

    Google Scholar 

  32. Kumagai A, Tomioka H, Shida T, Takahashi T, Muranaka M (1980) Clinical evaluation of a new orally active anti-anaphylactic compound: Ketotifen (HC 20–511) in Japanese adult asthmatics. Schweiz Med Wochenschr 110: 197–203

    Google Scholar 

  33. Lane DJ (1980) A steroid sparing effect of ketotifen in steroid-dependent asthmatics. Clin Allergy 10: 519–525

    Google Scholar 

  34. Lebeau B, Gence B, Bourdain M, Loria Y (1982) Le ketotifen dans le traitement preventif de l'asthme. Poumon-Coeur 38: 125–129

    Google Scholar 

  35. Lichtenstein LM, Margolis S (1968) Histamine release in vitro: Inhibition by catecholamines and methylxanthines. Science 161: 902–903

    Google Scholar 

  36. Kaliner M, Austen KF (1973) A sequence of biochemical events in the antigen-induced release of chemical mediators from sensitized human lung tissue. J Exp Med 138: 1077–1094

    Google Scholar 

  37. Butchers PR, Skidmore IF, Vardey CJ, Wheeldon A (1980) Characterization of the receptor mediating the anti-anaphylactic effects ofβ-adrenoceptor agonists in human lung tissue in vitro. Br J Pharmacol 71: 663–667

    Google Scholar 

  38. Petersson BA (1984) Sustained inhibition of antigen-induced histamine release from human lung by theβ 2-adrenoceptor agonist terbutaline. Allergy 39: 351–357

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Biochemical Research Laboratory, Medizinische Klinik und Poliklinik, Division of Renal and Hypertensive Diseases, University of Essen, Essen, Germany

    O. E. Brodde, U. Howe & M. C. Michel

  2. Ruhrlandklinik Essen, Essen, Germany

    S. Egerszegi & N. Konietzko

Authors
  1. O. E. Brodde
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. U. Howe
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Egerszegi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. N. Konietzko
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. C. Michel
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Brodde, O.E., Howe, U., Egerszegi, S. et al. Effect of prednisolone and ketotifen onβ 2-adrenoceptors in asthmatic patients receivingβ 2-bronchodilators. Eur J Clin Pharmacol 34, 145–150 (1988). https://doi.org/10.1007/BF00614551

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00614551

Key words

Search

Navigation