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A protective role for protease-activated receptors in the airways

Author

Listed:
  • T. M. Cocks

    (Departments of Pharmacology)

  • B. Fong

    (Departments of Pharmacology)

  • J. M. Chow

    (Departments of Pharmacology)

  • G. P. Anderson

    (Departments of Pharmacology)

  • A. G. Frauman

    (University of Melbourne)

  • R. G. Goldie

    (University of Western Australia)

  • P. J. Henry

    (University of Western Australia)

  • M. J. Carr

    (University of Western Australia)

  • J. R. Hamilton

    (Departments of Pharmacology)

  • J. D. Moffatt

    (Departments of Pharmacology)

Abstract

The protection of cells in the upper intestine against digestion by pancreatic trypsin depends on the prostanoid prostaglandin E2 (PGE2) and is mediated by protease-activated receptors in the epithelium1,2. As the airway epithelium is morphologically similar and also expresses one of these receptors, PAR2 (ref. 3), and is a major source of PGE2 (ref. 4), we reasoned that bronchial epithelial PAR2 might also participate in prostanoid-dependent cytoprotection in the airways. Here we show that activation of PAR2, which co-localizes immunohistochemically with trypsin(ogen) in airway epithelium, causes the relaxation of airway preparations from mouse, rat, guinea-pig and humans by the release of a cyclooxygenase product from the epithelium. This physiological protective response in isolated airways also occurred in anaesthetized rats, where activation of PAR2 caused a marked and prolonged inhibition of bronchoconstriction. After desensitization of PAR2, the response to trypsin recovered rapidly by mechanisms dependent on de novo synthesis and trafficking of proteins. Our results indicate that trypsin released from the epithelium can initiate powerful bronchoprotection in the airways by activation of epithelial PAR2.

Suggested Citation

  • T. M. Cocks & B. Fong & J. M. Chow & G. P. Anderson & A. G. Frauman & R. G. Goldie & P. J. Henry & M. J. Carr & J. R. Hamilton & J. D. Moffatt, 1999. "A protective role for protease-activated receptors in the airways," Nature, Nature, vol. 398(6723), pages 156-160, March.
    • Handle: RePEc:nat:nature:v:398:y:1999:i:6723:d:10.1038_18223
    DOI: 10.1038/18223
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