Complementary mechanisms of enhanced oxytocin-stimulated prostaglandin E-2synthesis in rabbit amnion at the end of gestation

The up-regulation of oxytocin (OT) receptors in rabbit amnion at the end of gestation is associated with a large increase in the ability of OT to stim ulate PGE(2) synthesis. The purpose of these investigations was to determin e what other factors contribute to this increase. OT enhanced PGE(2) synthe sis at several levels. The concentrations of cytosolic phospholipase A(2), which generates arachidonic acid for PGE(2) synthesis, and PGH endoperoxide synthases (types 1 and 2), which catalyze the conversion of arachidonic ac id to prostanoids, rose substantially in rabbit amnion at term. OT stimulat ed translocation of cytosolic phospholipase A(2) to the cell particulate fr action, presumably by a Ca2+-mediated process, and phosphorylation of cytos olic phospholipase A(2) via the extracellular regulated protein kinase 2/1- mediated pathway. OT-stimulated increases in intracellular Ca2+ concentrati ons and extracellular regulated protein kinase 2/1 phosphorylation were bot h mediated by G(q/11), activation. OT also increased the expression of PGH endoperoxide synthase-2 after treatment of amnion cells in culture for 2 h; however, PGE(2) release in response to OT was virtually immediate. These f indings show that the rapid stimulation of PGE(2) synthesis by OT occurs th rough cytosolic phospholipase A(2) activation and PGH endoperoxide synthase -1 activity, both of which, along with OT receptor concentrations, are cons iderably up-regulated in the amnion at the end of gestation.