Complementary mechanisms of enhanced oxytocin-stimulated prostaglandin E₂ synthesis 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 stimulate PGE₂ synthesis. The purpose of these investigations was to determine what other factors contribute to this increase. OT enhanced PGE₂ synthesis at several levels. The concentrations of cytosolic phospholipase A₂, which generates arachidonic acid for PGE₂ synthesis, and PGH endoperoxide synthases (types 1 and 2), which catalyze the conversion of arachidonic acid to prostanoids, rose substantially in rabbit amnion at term. OT stimulated translocation of cytosolic phospholipase A₂ to the cell particulate fraction, presumably by a Ca²⁺-mediated process, and phosphorylation of cytosolic phospholipase A₂ via the extracellular regulated protein kinase 2/1-mediated pathway. OT-stimulated increases in intracellular Ca²⁺ concentrations and extracellular regulated protein kinase 2/1 phosphorylation were both 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, PGE₂ release in response to OT was virtually immediate. These findings show that the rapid stimulation of PGE₂ synthesis by OT occurs through cytosolic phospholipase A₂ activation and PGH endoperoxide synthase-1 activity, both of which, along with OT receptor concentrations, are considerably up-regulated in the amnion at the end of gestation.