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Expression and function of proteinase-activated receptor 2 in human bronchial smooth muscle

Schmidlin, F., Amadesi, S., Vidil, R., Trevisani, M., Martinet, N., Caughey, G., Tognetto, M., Cavallesco, G., Mapp, C., Geppetti, P. and Bunnett, N. W. (2001) Expression and function of proteinase-activated receptor 2 in human bronchial smooth muscle. American Journal of Respiratory and Critical Care Medicine, 164 (7). pp. 1276-1281. ISSN 1535-4970

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To link to this item DOI: 10.1164/ajrccm.164.7.2101157

Abstract/Summary

Trypsin and mast cell tryptase cleave proteinase-activated receptor 2 (PAR2) to induce alterations in contraction of airway smooth muscle that have been implicated in asthma in experimental animals. Although tryptase inhibitors are under development for treatment of asthma, little is known about the localization and function of PAR2 in human airways. We detected PAR2 expression in primary cultures of human airway smooth muscle cells using reverse transcriptase/polymerase chain reaction (RT-PCR) and immunofluorescence. The PAR2 agonists trypsin, tryptase, and an activating peptide (SLIGKV-NH2) stimulated calcium mobilization in these cells. PAR2 agonists strongly desensitized responses to a second challenge of trypsin and SLIGKV-NH2, but not to thrombin, indicating that they activate a receptor distinct from the thrombin receptors. Immunoreactive PAR2 was detected in smooth muscle, epithelium, glands, and endothelium of human bronchi. Trypsin, SLIGKV-NH2, and tryptase stimulated contraction of isolated human bronchi. Contraction was increased by removal of the epithelium and diminished by indomethacin. Thus, PAR2 is expressed by human bronchial smooth muscle where its activation mobilizes intracellular Ca2+ and induces contraction. These results are consistent with the hypothesis that PAR2 agonists, including tryptase, induce bronchoconstriction of human airway by stimulating smooth muscle contraction. PAR2 antagonists may be useful drugs to prevent bronchoconstriction.

Item Type:Article
Refereed:Yes
Divisions:No Reading authors. Back catalogue items
Faculty of Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology
ID Code:35821
Additional Information:Full text available at Pubmed (see related URLs)
Publisher:American Thoracic Society

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