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Delayed and persistent suppression of bronchoconstriction by trypsin in the airway lumen

¹ Disciplines of Physiology, and ² Microbiology and Immunology, School of Biomedical, Biomolecular and Chemical Sciences, University of Western Australia. ³ Western Australian Institute of Medical Research, Perth, Western Australia.

CORRESPONDENCE: H. W. Mitchell, Discipline of Physiology, School of Biomedical, Biomolecular and Chemical Sciences, University of Western Australia, Perth, Western Australia. Fax: 61 93801025. E-mail: mitchell{at}cyllene.uwa.edu.au

Keywords: Airway smooth muscle, protease-activated receptors, trypsin

Received: April 8, 2005
Accepted September 7, 2005

Mucosal trypsin, a protease-activated receptor (PAR) stimulant, may have an endogenous bronchoprotective role on airway smooth muscle. To test this possibility the effects of lumenal trypsin on airway tone in segments of pig bronchus were tested.

Bronchial segments from pigs were mounted in an organ chamber containing Kreb's solution. Contractions were assessed from isovolumetric lumen pressure induced by acetylcholine (ACh) or carbachol added to the adventitia.

Trypsin, added to the airway lumen (300 µg·mL^–1), had no immediate effect on smooth muscle tone but suppressed ACh-induced contractions after 60 min, for at least 3 h. Synthetic activating peptides (AP) for PAR₁, PAR₂ or PAR₃ were without effect, but PAR₄ AP caused rapid, weak suppression of contractions. Lumenal thrombin was without effect and did not prevent the effects of trypsin. Effects of trypsin were reduced by N-nitro-L-arginine methyl ester but not indomethacin. Trypsin, thrombin and PAR₄ AP released prostaglandin E2. Adventitially, trypsin, thrombin and PAR₄ AP (but not PAR₂ AP) relaxed carbachol-toned airways after <3 min.

The findings of this study show that trypsin causes delayed and persistent bronchoprotection by interacting with airway cells accessible from the lumen. The signalling mechanism may involve nitric oxide synthase but not prostanoids or protease-activated receptors.