The mechanisms underlying the stimulatory effects of thrombin on myometrial smooth muscle

OBJECTIVE: The mechanisms underlying the stimulation of uterine contraction s in the presence of intrauterine hemorrhage have not been well defined. Th rombin, a blood coagulation factor, activates membrane receptors to result in the stimulation of the phosphatidylinositol signaling pathway and the mo bilization of cytosolic calcium in platelets. Our studies sought to determi ne whether thrombin stimulates similar events in myometrial smooth muscle. STUDY DESIGN: Cytosolic calcium imaging and in vitro contraction studies we re performed with rat myometrial tissue. RESULTS: At a concentration range of 1 to 100 U/mL thrombin produced phasic myometrial contractions, which were comparable in intensity to those produ ced by oxytocin and prostaglandin F-2 alpha. Thrombin-induced cytosolic cal cium concentration oscillations were similar to those produced by oxytocin. Contractions stimulated by thrombin were significantly suppressed in respo nse to inhibitors of the phosphatidylinositol signaling pathway. These stud ies also confirmed that membrane receptor-Go protein coupling events play a more important role than tyrosine kinase-mediated events during thrombin s timulation of myometrial smooth muscle. CONCLUSION: Thrombin is a potent uterotonic agonist, and its effects in myo metrium are mediated by intracellular signaling events comparable to those activated by classic uterotonic agents. The physiologic importance of throm bin appears to be related to its potential role in the stimulation of uteri ne contractions in the presence of intrauterine hemorrhage.