Enhanced contractile response to thrombin in the pregnant rat myometrium

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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 Ca2+ concentration ([Ca2+]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 [Ca2+]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 Ca2+‐free PSS, thrombin induced no increase in [Ca2+]i and tension in the pregnant myometrium. Both diltiazem (10 μM) and SK‐F 96365 (10 μM) significantly inhibited the thrombin‐induced elevations of [Ca2+]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. British Journal of Pharmacology (2000) 131, 1619–1628; doi:10.1038/sj.bjp.0703729