Enhanced contractile response to thrombin in the pregnant rat myometrium.

Abstract

Thrombin causes various cellular events by activating protease-activated receptors (PARs). Here, we showed, for the first time, that thrombin induced myometrial contraction. To determine the mechanism of thrombin-induced myometrial contraction, we simultaneously measured intracellular Ca(2+) concentration ([Ca(2+)](i)) and tension of fura-PE3-loaded rat myometrium using front-surface fluorimetry. The expression of thrombin receptor mRNA in the rat myometrium were determined by reverse transcription-polymerase chain reaction analysis (RT - PCR analysis). Thrombin (0.01 - 3 u ml(-1)) caused dose-dependent increase in [Ca(2+)](i) and tension in the rat myometrium, and this effect was greatly enhanced in the pregnant myometrium. PAR1-activating peptide mimicked the effects of thrombin. In Ca(2+)-free PSS, thrombin induced no increase in [Ca(2+)](i) and tension in the pregnant myometrium. Both diltiazem (10 microM) and SK-F 96365 (10 microM) significantly inhibited the thrombin-induced elevations of [Ca(2+)](i) and tension, and their effects were additive. RT - PCR analysis revealed an approximately 10 fold increase in the level of thrombin receptor mRNA in the pregnant myometrium compared to that obtained in the non-pregnant myometrium. In conclusion, the contractile response to thrombin was greatly enhanced in the pregnant myometrium, mainly due to the up-regulation of thrombin receptor. We propose that initiation of a post-parturitional myometrial contraction is one of the most important physiological roles of thrombin receptor.