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Comparison of parameters of in vitro lymphocyte β2-adrenoceptor function in normal and asthmatic subjects

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Summary

There is conflicting data in the literature as to whether subsensitivity of in-vivo β2-adrenoceptor (β2-AR) responses in patients with asthma is due to an endogenous defect of β2-AR or an effect of exogenous β2-agonist therapy. The purpose of the study was to compare in-vitro parameters of lymphocyte β2-AR function in eight age and sex matched normal [FEV1, 98 (2) % predicted] volunteers and asthmatic [FEV1, 60 (5) % predicted] subjects. The asthmatic group were washed out for 4 weeks by substituting inhaled β2-agonist therapy with ipratropium bromide, in order to exclude possible exogenous effects of β2-agonist exposure. Receptor binding affinity (Kd) and density (Bmax) were evaluated using (-)125I-iodocyanopindolol and maximal cAMP response (Emax) was assayed following stimulation with isoprenaline (10−4M).

No significant differences were found between the normal and asthmatic group for Kd (pmol·l−1): 9.65 vs 10.2, Bmax (fmol/106 cells): 1.9 vs 1.6, or Emax (pmol/106 cells): 4.24 vs 4.85.

Thus, parameters of β2-AR function are unaltered in asthmatic patients who have not been exposed to β2-agonists, suggesting that asthma is not associated with an endogenous defect of β2-AR.

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References

  • Brodde OE, Howe U, Egerszegi S, Konietzko N, Michel MC (1988) Effect of prednisolone and ketotifen on β2-adrenoceptors in asthmatic patients receiving β2-bronchodilators. Eur J Clin Pharmacol 34: 145–150

    Google Scholar 

  • Brooks SM, McGowan K, Bernstein IL, Altenau P, Peagler J (1979) Relationship between numbers of beta adrenergic receptors in lymphocytes and disease severity in asthma. J Allergy Clin Immunol 63: 401–406

    Google Scholar 

  • Brown PH, Blundell G, Greening AP, Crompton GK (1990) Do large volume spacer devices reduce the systemic effects of high dose inhaled corticosteroids? Thorax 45: 736–739

    Google Scholar 

  • Brown PH, Blundell G, Greening AP, Crompton GK (1991) Hypothalamic-pituitary-adrenal axis suppression in asthmatics inhaling high dose corticosteroids. Resp Med 85: 501–510

    Google Scholar 

  • Connolly ME, Greenacre JK (1976) The lymphocyte β-adrenoceptor in normal subjects and patients with bronchial asthma. J Clin Invest 58: 1307–1316

    Google Scholar 

  • Connolly MJ, Crowley JJ, Nielson CP, Charan NB, Vestal RE (1992) Relationships between non-specific bronchial responsiveness to methacholine and peripheral mononuclear leukocyte beta-adrenergic receptor function in young drug-naive subjects. Am Rev Respir Dis 146: 592–597

    Google Scholar 

  • Ebden P, Jenkins A, Houston G, Davies BH (1986) Comparison of two high dose corticosteroid aerosol treatments, beclomethasone diproprionate (1500 μg/day) and budesonide (1600 μg/day) for chronic asthma. Thorax 41: 869–874

    Google Scholar 

  • Hauck RW, Bohm M, Gengebach MS, Sunder-Plassmann L, Fruhmann G, et al (1990) β2-adrenoceptors in human lung and peripheral mononuclear leukocytes of untreated and terbutaline-treated patients. Chest 9: 376–381

    Google Scholar 

  • Johansson SA, Anderson KE, Brattsand R, Gruvstad E, Hedner P (1982) Topical and systemic glucocorticoid potencies of budesonide and beclomethasone diproprionate in man. Eur J Clin Pharmacol 22: 523–529

    Google Scholar 

  • Kariman K (1980) β-adrenergic receptor binding in lymphocytes from patients with asthma. Lung 158: 41–51

    Google Scholar 

  • Lipworth BJ, Clark RA, Dhillon DP, McDevitt DG (1990) Subsensitivity of β-adrenoceptor responses in asthmatic patients taking regular low-dose inhaled salbutamol. Eur J Clin Pharmacol 38: 203–205

    Google Scholar 

  • Lipworth BJ, Struthers AD, McDevitt DG (1989) Tachyphylaxis to systemic but not airways responses during prolonged therapy with high dose inhaled salbutamol in asthmatics. Am Rev Respir Dis 140: 586–592

    Google Scholar 

  • Logsdon PJ, Middleton E, Coffey RG (1972) Stimulation of leukocyte adenyl cyclase by hydrocortisone and isoproterenol in asthmatic and non asthmatic subjects. J Allergy Clin Immunol 50: 45–56

    Google Scholar 

  • Molema J, Lammers JWJ, van Herwaarden CLA, Folgering HTM (1988) Effects of inhaled beclomethasone depropionate on β2-receptor function in the airways and adrenal responsiveness in bronchial asthma. Eur J Clin Pharmacol 34: 577–583

    Google Scholar 

  • Morris HG, Rusnak SA, Barzens K (1977) Leukocyte cyclic adenosine monophosphate in asthmatic children: effects of adrenergic therapy. Clin Pharmacol Ther 22: 352–357

    Google Scholar 

  • Parker CW, Smith JW (1973) Alterations in cyclic adenosine monophosphate metabolism in human bronchial asthma. I. Leukocyte responsiveness to β2-adrenergic agents. J Clin Invest 52: 48–59

    Google Scholar 

  • Parker CW, Huber MG, Baumann ML (1973) Alterations in cyclic AMP metabolism in human bronchial asthma. III. Leukocyte and lymphocyte response to steroids. J Clin Invest 52: 1342–1348

    Google Scholar 

  • Rahman ARA, McDevitt DG, Struthers AD, Lipworth BJ (1992) Sex-differences in hypokalaemic and electrocardiographic effects of inhaled terbutaline. Thorax 47: 1056–1059

    Google Scholar 

  • Sano Y, Watt G, Townley RG (1983) Decreased mononuclear cell beta-adrenergic receptors in bronchial asthma: parallel studies of lymphocyte and granulocyte desensitization. J Allerg Clin Immunol 72: 495–503

    Google Scholar 

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

    Google Scholar 

  • Whicker SD, Armour CL, Black JL (1988) Responsiveness of bronchial smooth muscle from asthmatic patients to relaxant and contractile agents. Pulm Pharmacol 1: 25–31

    Google Scholar 

  • Wolfe RN, Hui KK, Connolly MD, Tashkin DP, Fisher HK (1982) A study of beta-adrenergic and prostaglandin receptors in patients with aspirin-induced bronchospasm. J Allerg Clin Immunol 69: 46–50

    Google Scholar 

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Newnham, D.M., Coutie, W.J.R., McFarlane, L.C. et al. Comparison of parameters of in vitro lymphocyte β2-adrenoceptor function in normal and asthmatic subjects. Eur J Clin Pharmacol 45, 535–538 (1993). https://doi.org/10.1007/BF00315310

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  • DOI: https://doi.org/10.1007/BF00315310

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