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1 Department of Pharmacology and 2 Department of Physiology and Kolling Institute, University of Sydney, New South Wales 2006, Australia
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, trypsin, or the PAR-2
activating peptide (AP). Trypsin and the PAR-2 AP induced contractions
in human isolated airways, and these contractions were potentiated in
the presence of the cyclooxygenase (COX) inhibitor indomethacin.
Trypsin also increased the contractions to histamine in airways from
sensitized (allergic) patients but not from nonsensitized (nonallergic)
patients. Tryptase purified from human lung, skin and lung recombinant
-tryptases, 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 the PAR-2 AP did not induce PGE2
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 contractions to
histamine, and induce proliferation and therefore may contribute to
airway diseases such as asthma.
tryptase; proliferation; contraction
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