title: Delayed and persistent suppression of bronchoconstriction by trypsin in the airway lumen.
abstract: 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 microg x 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(omega)-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.
authors.affiliation: Discipline of Physiology, School of Biomedical, Biomolecular and Chemical Sciences, University of Western Australia, Perth, Western Australia.
authors.forename: A
authors.initials: A
authors.lastname: Sharma
authors.forename: H L
authors.initials: HL
authors.lastname: Goh
authors.forename: N
authors.initials: N
authors.lastname: Asokananthan
authors.forename: A
authors.initials: A
authors.lastname: Bakker
authors.forename: G A
authors.initials: GA
authors.lastname: Stewart
authors.forename: H W
authors.initials: HW
authors.lastname: Mitchell
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects*; D016009:Chi-Square Distribution; D004558:Electric Stimulation; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; D013552:Swine; D014357:Trypsin / Q000494:pharmacology*
chemical_list: D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; D014357:Trypsin