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, 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 beta-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 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 contractions to histamine, and induce proliferation and therefore may contribute to airway diseases such as asthma.
Chambers
L S
LS
Department of Pharmacology, University of Sydney, New South Wales 2006, Australia. lindac@pharmacol.usyd.edu.au
Black
J L
JL
Poronnik
P
P
Johnson
P R
PR
D000328:Adult; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology*; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000494:pharmacology*; D053802:Tryptases
D018836:Inflammation Mediators; D009842:Oligopeptides; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin; C112356:seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide; D011451:Prostaglandin-Endoperoxide Synthases; D012697:Serine Endopeptidases; D053802:Tryptases; D015232:Dinoprostone; D002118:Calcium