Enhanced contractile response to thrombin in the pregnant rat myometrium

1 Thrombin causes various cellular events by activating protease-activated receptors (PARs). Here, we showed, for the first time, that thrombin induce d myometrial contraction. To determine the mechanism of thrombin-induced my ometrial contraction, we simultaneously measured intracellular Ca2+ concent ration ([Ca2+](i)) and tension of fura-PE3-loaded rat myometrium using fron t-surface fluorimetry. The expression of thrombin receptor mRNA in the rat myometrium were determined by reverse transcription-polymerase chain reacti on analysis (RT-PCR analysis). 2 Thrombin (0.01-3 u ml(-1)) caused dose-dependent increase in [Ca2+](i) an d tension in the rat myometrium, and this effect was greatly enhanced in th e pregnant myometrium. PAR1-activating peptide mimicked the effects of thro mbin. 3 In Ca2+-free PSS, thrombin induced no increase in [Ca2+](i) and tension i n the pregnant myometrium. Both diltiazem (10 muM) and SK-F 96365 (10 muM) significantly inhibited the thrombin-induced elevations of [Ca2+](i) and te nsion, and their effects were additive. 4 RT-PCR analysis revealed an approximately 10 fold increase in the level o f thrombin receptor mRNA in the pregnant myometrium compared to that obtain ed in the non-pregnant myometrium. 5 In conclusion, the contractile response to thrombin was greatly enhanced in the pregnant myometrium, mainly due to the up-regulation of thrombin rec eptor. We propose that initiation of a post-parturitional myometrial contra ction is one of the most important physiological roles of thrombin receptor .