HSY-EAl細胞におけるprotease-activated receptor (PAR)-1とPAR-2の相互脱感作機構

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The mechanisms for cross-desensitization between protease-activated receptor (PAR)-1 and PAR-2 in human parotid cell line, HSY-EA1 cells were examined. The HSY-EA1 cells strongly expressed mRNAs for PAR-1 and PAR-2, whereas the expression of PAR-3 and PAR-4 was very limited. Stimulation of HSY-EA1 cells with various concentrations of thrombin or trypsin produced a striking increase in [Ca^<2+>]_i followed by a slow return to the basal level within 2-3 min. When cells were pretreated with various concentrations of trypsin, the subsequent Ca^<2+> response with thrombin diminished in a dose-dependent manner over the trypsin concentration, indicating that trypsin desensitized PAR-1. The desensitization of the thrombin-induced Ca^<2+> response was also induced by the pretreatment with PAR-2 agonist peptide, SLIGKV. These results suggest that trypsin-induced inactivation of PAR-1 is due to the heterologous desensitization of PAR-1 through the activation of PAR-2 in addition to a proteolytic degradation of PAR-1.
北海道医療大学の論文