Protease-activated receptor-2-mediated Ca2+ signaling in guinea pig tracheal epithelial cells |
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Authors: | Oshiro Akihiro Otani Hitomi Yagi Yasuhiro Fukuhara Shirou Inagaki Chiyoko |
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Institution: | Department of Pharmacology, Kansai Medical University, 10-15, Fumizono-Cho, Osaka 570-8506, Moriguchi, Japan. |
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Abstract: | The protease-activated receptor-2 (PAR-2), a G protein-coupled receptor activated by trypsin, contributes to the pathogenesis of inflammatory disease including asthma. Here, we examined the mechanisms by which stimulation of PAR-2 induces an increase in intracellular Ca2+ concentration (Ca2+]i) in guinea pig tracheal epithelial cells. Trypsin (0.01-3 units/ml) dose-dependently induced a transient increase in Ca2+]i, the increase being blocked by soybean trypsin inhibitor (SBTI 1 microM). An increase in Ca2+]i was also induced by an agonist peptide for PAR-2 (SLIGRL-NH2, 0.001-10 microM) but not by thrombin (3 units/ml, an activator for PAR-1, PAR-3 or PAR-4). Repeated or cross stimulation of trypsin or SLIGRL-NH2 caused marked desensitization of the Ca2+]i response. These responses of Ca2+]i to trypsin and SLIGRL-NH2 were attenuated by a phospholipase C inhibitor, U-73122, and a Ca2+-ATPase inhibitor, thapsigargin (100 nM), while removal of Ca2+ and a L-type Ca2+-channel blocker, verapamil, were without significant effects. Further, trypsin was without effect on the rate of fura 2 quenching by Mn2+ entry as an indicator of Ca2+ influx. Thus, stimulation of PAR-2 appears to increase Ca2+]i through the mobilization of Ca2+ from intracellular stores probably via phospholipase Cbeta-linked generation of a second messenger. |
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Keywords: | Tracheal epithelial cell Protease-activated receptor Trypsin Intracellular Ca2+ Phosphoinositide |
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