Functional effects of protease-activated receptor-2 stimulation on human airway smooth muscle

The protease-activated receptor (PAR)-2 is present on the smooth muscle and epithelium of human airways and can be activated by mast cell tryptase, tr ypsin, or the PAR-2 activating peptide (AP). Trypsin and the PAR-2 AP induc ed contractions in human isolated airways, and these contractions were pote ntiated in the presence of the cyclooxygenase (COX) inhibitor indomethacin. Trypsin also increased the contractions to histamine in airways from sensi tized (allergic) patients but not from nonsensitized (nonallergic) patients . Tryptase purified from human lung, skin and lung recombinant beta -trypta ses, trypsin, and the PAR-2 AP all increased DNA synthesis in human airway smooth muscle (HASM) cells. Activation of PAR-2 by tryptase, trypsin, and t he PAR-2 AP did not induce PGE(2) release from HASM cells. Trypsin and the PAR-2 AP increased the levels of intracellular calcium in HASM cells, with desensitization evident after treatment with either agonist. In conclusion, activation of PAR-2 can induce contractions of human airways, potentiate c ontractions to histamine, and induce proliferation and therefore may contri bute to airway diseases such as asthma.