Review
Phosphodiesterase 4 and tolerance to β2-adrenoceptor agonists in asthma

https://doi.org/10.1016/0165-6147(96)10039-0Get rights and content

Abstract

β2-Adrenoceptor agonists provide a mainstay in the treatment of asthma worldwide. However, despite their ability to provide symptomatic relief, chronic or repeated exposure to β2-adrenoceptor agonists does not resolve asthmatic inflammation, because of the rapid development of tolerance by pro-inflammatory and immune cells of the lung. The prevailing belief is that tolerance to the so-called non-bronchodilator actions of β2-adrenoceptor agonists is largely attributable to direct receptor desensitization mediated by G protein receptor-coupled kinases and/or cAMP-dependent protein kinase. Here, Mark Giembycz suggests another, largely ignored, explanation for β2-adrenoceptor desensitization that is based on the accelerated degradation of cAMP by Phosphodiesterase.

References (62)

  • P.J. Barnes et al.

    Trends Pharmacol. Sci.

    (1992)
  • D.W. Cockcroft et al.

    Lancet

    (1993)
  • M. Bouvier

    J. Biol. Chem.

    (1989)
  • M.J. Lohse

    Biochem. Biophys. Acta

    (1993)
  • T.T. Chuang et al.

    J. Biol. Chem.

    (1992)
  • M.D. Bates

    J. Biol. Chem.

    (1993)
  • J.V. Swinnen et al.

    J. Biol. Chem.

    (1991)
  • M.M. van Lookeren Campagne

    J. Biol. Chem.

    (1990)
  • M.A. Giembycz

    Biochem. Pharmacol.

    (1992)
  • L. Monaco et al.

    J. Biol. Chem.

    (1994)
  • C. Sette et al.

    J. Biol. Chem.

    (1994)
  • C. Sette et al.

    J. Biol. Chem.

    (1994)
  • T.J. Torphy

    J. Biol. Chem.

    (1995)
  • P. Engels et al.

    FEBS Lett.

    (1994)
  • K. Okonogi

    J. Biol. Chem.

    (1991)
  • L. Valette

    Biochem. Biophys. Res. Contmun.

    (1990)
  • S-H. Li et al.

    J. Invest. Dermatol.

    (1992)
  • A.E. Michael et al.

    Mol. Cell Endocrinol.

    (1991)
  • S.C. Chan et al.

    J. Allergy Clin. Immunol.

    (1985)
  • S. Grewe et al.

    J. Allergy Clin. Immunol.

    (1982)
  • C.A. Holden et al.

    J. Invest. Dermatol.

    (1986)
  • J. Butler et al.

    J. Allergy Clin. Immunol.

    (1983)
  • M. Bachelet et al.

    J. Allergy Clin. Immunol.

    (1991)
  • M. Johnson et al.

    Clin. Exp. Allergy

    (1992)
  • P.J. Barnes

    Annu. Rev. Med.

    (1993)
  • F.P. Nijkamps et al.

    Physiol. Rev.

    (1992)
  • P.J. Barnes

    Am. J. Respir. Crit. Care Med.

    (1995)
  • B.J. O'Connor et al.

    New Engl. J. Med.

    (1992)
  • P.V. Gardiner

    Am. J. Respir. Crit. Care Med.

    (1994)
  • R.T. Premont et al.

    FASEB J.

    (1995)
  • M.J. Loshe et al.

    Science

    (1990)
  • Cited by (0)

    View full text