Thrombin and PAR1-activating peptide: Effects on human uterine contractility in vitro

Objective: Thrombin enhances uterine contractions in animal models, which is an effect that is mediated through protease-activated receptors. The aims of this study were to investigate the effects of thrombin on spontaneous human uterine contractility in vitro, in tissue obtained in the presence and absence of pregnancy, and to investigate the effects of a specific protease-activated receptor 1-activating peptide on human pregnant myometrial contractility. Study design: Isometric recordings were performed under physiologic conditions on myometrial strips that were obtained from elective cesarean delivery and premenopausal hysterectomy specimens. The effects of thrombin (0.5 to 5.0 U/mL) and a specific protease-activated receptor 1-activating peptide (1 nmol/L to 10 μmol/L) on integrals of contractile activity were measured and compared with control values. Results: Thrombin exerted a potent stimulatory effect on human myometrial contractility. For pregnant and nonpregnant myometrium, this effect was significant at concentrations of ≥ 3.0 U/mL and 1.0 U/mL, respectively, with net maximal stimulatory effects of 44.5% (5.0 U/mL, P < .001) and 40.42% (3.0 U/mL, P < .001), respectively. The protease-activated receptor 1-activating peptide also mediated a significant uterotonic effect (55.1% increase) on human pregnant myometrial contractility at 10 μmol/L concentration (P < .001). Conclusion: This uterotonic effect of thrombin suggests that it may play a role in the pathophysiologic condition of human uterine contractions in association with intrauterine bleeding. The similar uterotonic effect that is elicited by protease-activated receptor 1-activating peptide suggests a major role for protease-activated receptor-1 in the thrombin-mediated contractile effect.