Oxytocic activity of thrombin: Modulation of thrombin-induced gravid rat myometrial contractions by 5-hydroxytryptamine receptor antagonists

Abstract

Background: Thrombin possesses potent oxytocic activity in vitro and in vivo. This activity has been proposed to play a role in post-parturitional uterine contractions and possibly, preterm birth related to intrauterine hemorrhage. Previous workers have demonstrated that cyclo-oxygenase pathway may not play a significant role in oxytocic activity of thrombin. However, the role of 5-hydroxytryptamine (a mediator of some of the biological activities of thrombin) in the oxytocic activity of thrombin is unknown. The present study therefore aimed to examine the possible involvement of 5-hydroxytryptamine in thrombin-induced myometrial contractions. Methods: Effect of 5-hydroxytryptamine receptor antagonists on thrombin-induced contractions of isolated gravid rat myometrium was studied using isolated tissue bath system. Results: Thrombin-induced myometrial contractions were significantly and concentration-dependently inhibited by ketanserin and methysergide. Furthermore, 12±2% increase in the force of contractions of gravid rat myometrium pre-contracted with 5-hydroxytryptamine (1 μM) was provoked by 1 U/ml of thrombin. Thrombin-induced augmentation of the uterine stimulating effect of 5-hydroxytryptamine was characterized by pronounced increase in the contractile tone. Conclusions: 5-hydroxytryptamine may possibly play a role in oxytocic activity of thrombin. Uterine hyperactivity associated with intrauterine hemorrhage could hence involve thrombin-induced 5-hydroxytryptamine production in the uterus.