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

• Published in: American journal of obstetrics and gynecology Vol. 183; no. 3; pp. 674 - 681
• Main Authors: Elovitz, Michal A., Ascher-Landsberg, Jessica, Saunders, Trevania, Phillippe, Mark
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA Elsevier Inc 01.09.2000; Elsevier
• Subjects: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester - pharmacology; Animals; Biological and medical sciences; Calcium - metabolism; Calcium Channel Agonists - pharmacology; Cytosol - metabolism; Cytosolic calcium oscillations; Diglycerides - metabolism; Dinoprost - pharmacology; Female; Female genital diseases; GTP-Binding Protein alpha Subunits, Gq-G11; GTP-Binding Proteins - physiology; Gynecology. Andrology. Obstetrics; Inositol Phosphates - metabolism; Isoenzymes - metabolism; Medical sciences; Muscle, Smooth - drug effects; Myometrium - drug effects; Non tumoral diseases; Oxytocin - pharmacology; phasic myometrial contractions; Phosphatidylinositol 4,5-Diphosphate - metabolism; phosphatidylinositol signaling pathway; protease activated receptors; Rats; Rats, Sprague-Dawley; thrombin; Thrombin - administration & dosage; Thrombin - pharmacology; Type C Phospholipases - metabolism; Uterine Contraction - drug effects; Cytosolic calcium oscillations; thrombin; phasic myometrial contractions; protease activated receptors; phosphatidylinositol signaling pathway; Human; Myometrium; Serine endopeptidases; Pathophysiology; Enzyme; Cardiovascular disease; Thrombin; Activation; Muscle contraction; Hemorrhage; Female genital diseases; Peptidases; Membrane receptor; Uterus; Female genital system; Hydrolases; Female
• ISSN: 0002-9378; 1097-6868
• DOI: 10.1067/mob.2000.106751

Objective: The mechanisms underlying the stimulation of uterine contractions in the presence of intrauterine hemorrhage have not been well defined. Thrombin, a blood coagulation factor, activates membrane receptors to result in the stimulation of the phosphatidylinositol signaling pathway and the mobilization of cytosolic calcium in platelets. Our studies sought to determine whether thrombin stimulates similar events in myometrial smooth muscle. Study Design: Cytosolic calcium imaging and in vitro contraction studies were 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 produced by oxytocin and prostaglandin F2α. Thrombin-induced cytosolic calcium concentration oscillations were similar to those produced by oxytocin. Contractions stimulated by thrombin were significantly suppressed in response to inhibitors of the phosphatidylinositol signaling pathway. These studies also confirmed that membrane receptor–Gq protein coupling events play a more important role than tyrosine kinase–mediated events during thrombin stimulation of myometrial smooth muscle. Conclusion: Thrombin is a potent uterotonic agonist, and its effects in myometrium are mediated by intracellular signaling events comparable to those activated by classic uterotonic agents. The physiologic importance of thrombin appears to be related to its potential role in the stimulation of uterine contractions in the presence of intrauterine hemorrhage. (Am J Obstet Gynecol 2000;183:674-81.)