The mechanisms underlying the stimulatory effects of thrombin on myometrial smooth muscle
Abstract
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 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.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.
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Thrombin has uterotonic effects that may lead to rupture of membranes and uterine contractions.
“These factors, coupled with the uterotonic effects of thrombin (20), may lead to rupture of membranes and uterine contractions.”
From Placental abruption at near-term and term gestations: Pathophysiology, epidemiology, diagnosis, and management (2023) · cites this paper as [20]
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- Authors
- Elovitz, M. A., Ascher-Landsberg, J., Saunders, T., & Phillippe, M.
- Affiliations
- University of Chicago (US)
- Venue
- American Journal of Obstetrics and Gynecology
- Publisher
- Elsevier BV
- Published
- 2000-09
- Volume
- 183
- Issue
- 3
- Pages
- 674-681
- ISSN
- 0002-9378 (ISSN-L)
- OpenAlex
- W2068318750
- Cited by
- 94
- References
- 30
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 7 · 2022: 5 · 2021: 1 · 2020: 1 · 2019: 5 · 2018: 1 · 2017: 2 · 2015: 2 · 2014: 4 · 2013: 5 · 2012: 6
- FWCI
- 1.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Obstetrics and Gynecology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hd032449-04)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD28506, R01HD028506, HD32449)
- Topics
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- thrombin, uterine contraction, uterotonic agents, phosphoinositide signaling, cytosolic calcium oscillations, oxytocin, prostaglandin F2alpha, intrauterine hemorrhage, cell surface receptors
- MeSH terms
- Animals, 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester, Calcium, Calcium Channel Agonists, Cytosol, Diglycerides, Female, Inositol Phosphates, Isoenzymes, Muscle, Smooth, Myometrium, Oxytocin, Type C Phospholipases, Thrombin, Uterine Contraction, Dinoprost, Rats, Sprague-Dawley, GTP-Binding Proteins, Phosphatidylinositol 4,5-Diphosphate, GTP-Binding Protein alpha Subunits, Gq-G11, Rats
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