The hypothesis of this proposal is that MgS04 decrease myometrial contractility by interfering with the stimulatory effect of Ca2+ at intracellular locations. To test this hypothesis, the effects of MgS04 on specific steps in the contractile response of human myometrium will be evaluate; these studies will include: 1) simultaneously evaluating contractile force and cytosolic Ca2+ to determine the relationship between the ability of MgS04 to decrease contractility and to inhibit increases in cytosolic Ca2+; 2) determining if MgS04 inhibits activation of phospholipase C; 3) determining if MgS04 inhibits agonist-induced activation of protein kinase C; and 4) determining if MgS04 inhibits activation of myosin light chain kinase. For these studies strips of myometrium and cultured uterine myocytes will be obtained from pregnant women undergoing cesarean section deliveries, which are uncomplicated by infection or pharmacologic treatment for premature labor.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
1R01HD036692-01
Application #
2669661
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1998-07-01
Project End
2001-06-30
Budget Start
1998-07-01
Budget End
1999-06-30
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
005436803
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
Fomin, Victor P; Gibbs, Shawn G; Vanam, Ram et al. (2006) Effect of magnesium sulfate on contractile force and intracellular calcium concentration in pregnant human myometrium. Am J Obstet Gynecol 194:1384-90
Bermeo, Miguel E; Fomin, Victor P; Ventolini, Gary et al. (2004) Magnesium sulfate induces translocation of protein kinase C isoenzymes alpha and delta in myometrial cells from pregnant women. Am J Obstet Gynecol 190:522-7
Hurd, William W; Natarajan, Viswanathan; Fischer, John R et al. (2002) Magnesium sulfate inhibits the oxytocin-induced production of inositol 1,4,5-trisphosphate in cultured human myometrial cells. Am J Obstet Gynecol 187:419-24
Hurd, W W; Fomin, V P; Natarajan, V et al. (2000) Expression of protein kinase C isozymes in nonpregnant and pregnant human myometrium. Am J Obstet Gynecol 183:1525-31