Effect of protease-activated receptor-2-activating peptide on guinea pig airway resistance and isolated tracheal strips

Purpose: Protease-activated receptors (PARs) are a family of G-protein-coupled receptors distributed in a number of tissues. PAR-2 is expressed on airway epithelium and smooth muscles and overexpressed under pathological conditions, such as asthma and chronic obstructive pulmonary disease. However, the role of PAR-2 in airways has not yet been defined. In this study, we investigated the role of PAR-2-activating peptide (SLIGRL) on histamine-induced bronchoconstriction and the mechanisms underlying the bronchoprotective effect both in vivo and in vitro. Materials and Methods: The effect of SLIGRL was tested in vivo using histamine-induced bronchoconstriction in the guinea pig and in vitro using isolated tracheal spiral strips. Results: In vivo pretreatment with SLIGRL significantly reduced the histamine-induced increased bronchoconstriction. Neither propranolol nor vagotomy abolished the inhibitory effect of SLIGRL. Furthermore, indomethacin or glibenclamide did not antagonize the inhibitory response to SLIGRL. In isolated tracheal spiral strips in vitro, SLIGRL did not affect the contractile response to acetylcholine or potassium chloride; however, histamine-induced contraction was inhibited in a dose-dependent manner. Conclusion: Our data demonstrate the protective effect of SLIGRL in airways; however, this effect appears to be mediated independently of prostanoids, nitric oxide, circulating adrenaline, ATP-sensitive K + channels, and vagal stimulation.