Oxytocin stimulates prostaglandin F 2α secretion from porcine endometrial cells through activation of calcium-dependent protein kinase C☆

Abstract

The mechanism for oxytocin’s (OT) stimulation of PGF 2α secretion from porcine endometrium is not clear, but is thought to involve mobilization of intracellular Ca 2+ and subsequent activation of protein kinase C (PKC). This study determined: (1) if mobilization of inositol trisphosphate-sensitive Ca 2+ by thapsigargin or activation of PKC by phorbol 12-myristate 13-acetate (PMA) could stimulate PGF 2α release from luminal epithelial, glandular epithelial and stromal cells of porcine endometrium and (2) if inhibitors of various PKC isotypes could attenuate the ability of OT, thapsigargin and PMA to stimulate PGF 2α secretion from these cells. Thapsigargin and PMA each stimulated ( P < 0.01) PGF 2α secretion from all three endometrial cell types examined. However, the effects of thapsigargin and PMA were synergistic ( P < 0.05) only in stromal cells. Three protein kinase C inhibitors (i.e. Gö6976, Gö6983 and Ro-31-8220) differentially attenuated ( P < 0.05) the ability of OT, thapsigargin and PMA to stimulate PGF 2α release. These results are consistent with the hypothesis that OT mobilizes Ca 2+ to activate a Ca 2+-dependent PKC pathway to promote PGF 2α secretion from porcine endometrial cells. The differing pattern of response to isotype-specific inhibitors of PKC among cell types suggests that distinct PKC isoforms are differentially expressed in luminal epithelial, glandular epithelial and stromal cells.