Effect of trypsin on spontaneous uterine contractility in pregnant rat : possible involvement of protease-activated receptor 2

Abstract

This study was performed to evaluate the effect of protease-activated receptor (PAR)-2 on spontaneous myometrial contraction (SMC) in isolated term pregnant myometrial strips of rat and elucidate a cellular mechanism in such an effect using conventional voltage-clamp method. In isometric tension measurement, trypsin and SL-NH2, PAR-2 agonists, significantly augmented SMC in frequency and amplitude. But, boiled trypsin (BT) and LR-NH2 had no effect on SMC. These stimulatory effects of PAR-2 agonists on SMC was nearly completely prevented by pre-application of Bay K 8644, a L-type voltage-gated Ca2+ channel activator, showing involvement of L-type voltage-gated Ca2+ channel in PAR-2-induced augmentation of SMC. In addition, PAR-2 agonists significantly enhanced L-type voltage-gated Ca2+ current (ICa-L), measured by conventional voltage-clamp method and this increase was primarily mediated by activation of phospholipase C (PLC) and protein kinase C (PKC) via G-protein activation. Taken together, we demonstrate that PAR-2 actively regulate SMC during pregnancy by modulating Ca2+ influx through L-type voltage-gated Ca2+ channel and this increase of ICa-L is primarily mediated by PLC and PKC activation. These results suggest a cellular mechanism for pathophysiological effects of PAR-2 activation on myometrical contractility during pregnancy and provide basic and theoretical information about developing new agents for the treatment of premature labor and other obstetric complication.