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


METHODS
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 F(2)(alpha). 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.


CONCLUSIONS
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.
Elovitz
M A
MA
Department of Obstetrics and Gynecology, The University of Chicago, Chicago, IL 60637, USA.
Ascher-Landsberg
J
J
Saunders
T
T
Phillippe
M
M
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D015237:Dinoprost / Q000494:pharmacology; D005260:Female; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D019204:GTP-Binding Proteins / Q000502:physiology; D007295:Inositol Phosphates / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D009130:Muscle, Smooth / Q000187:drug effects*; D009215:Myometrium / Q000187:drug effects*; D010121:Oxytocin / Q000494:pharmacology; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013917:Thrombin / Q000008:administration & dosage / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000378:metabolism; D014590:Uterine Contraction / Q000187:drug effects*
C011439:1,2-diacylglycerol; D002120:Calcium Channel Agonists; D004075:Diglycerides; D007295:Inositol Phosphates; D007527:Isoenzymes; D019269:Phosphatidylinositol 4,5-Diphosphate; D010121:Oxytocin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D015237:Dinoprost; D010738:Type C Phospholipases; D013917:Thrombin; D019204:GTP-Binding Proteins; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D002118:Calcium