The release of oxytocin and prostaglandin appears to be the final step in the initiation of parturition. Myometrial sensitivity to oxytocin increases sharply shortly before parturition in both term and preterm pregnancy. We have shown that oxytocin stimulates prostaglandin biosyntehsis and relase in term pregnant uterus, in addition to its uterotonic action. We postulate that the marked increase in sensitivity of the parturient uterus to oxytocin may be related to the enhances prostaglandin biosynthesis and the oxytocin-induced prostaglandin release in the term pregnent uterus. We also believe that specific oxytocin antagonists may be effective as tocolytic agents for the treatment of preterm labor and prevention of premature birth. This proposed project is designed to test and explore these possibilities. One specific aim of thi project is to define the interactions between oxytocin and prostglandin in the uterus. We will determine thre relationship between oxytocin sensitivity and prostaglandin production at various gestational age in pregnant rats. Radiochemical assay, thin-layer chromatography and radioimmunoassay will be employed for identification and quantitation of prostaglandins. Cycly-oxygenase activity and prostaglandin binding will be studied in microsomal and plasma membrane fractions of rat uterine tissue by standard biochemical techiques. Another specific aim is to develop specific anti-oxytocin peptids as potential agents for the treatment of preterm labor. We will design, synthesize and test more specific, more potentn and longer-acting anti-oxytocin peptides. Promising agents will be evaluated on isolated pregnant human myometrial tissue preparations. Additionally, we will also investigate the potentials of prostaglanding synthetase inhibirots with anti-prostaglandin and anti-oxytocin activites as tocolytic agents.
NIH ExPorter
NIH ExPorter