INTRACELLULAR MECHANISMS UNDERLYING PROSTAGLANDIN F-2-ALPHA-STIMULATED PHASIC MYOMETRIAL CONTRACTIONS

These studies sought to test the hypothesis that prostaglandin F-2 alp ha (PGF(2 alpha))-stimulated phasic myometrial contractions are charac terized by the activation of the phosphatidylinositol-signaling pathwa y resulting in the generation of cytosolic calcium oscillations. For t he experiments described in this report rat myometrial tissue was used , after the tissue was loaded with fura 2, to perform cytosolic calciu m imaging studies and to perform computer-digitalized in vitro isometr ic contraction studies. Consistent with the above hypothesis, the cyto solic calcium-imaging studies demonstrated PGF(2 alpha)-stimulated cyt osolic calcium oscillations occurring simultaneously with phasic contr actions. The in vitro isometric contraction studies confirmed that pre viously reported inhibitors of the phosphatidylinositol-signaling path way and cytosolic calcium oscillation mechanisms resulted in significa nt inhibition of PGF(2 alpha)-stimulated phasic myometrial contraction s. In summary, these studies have provided substantial support for the hypothesis that PGF(2 alpha)-stimulated phasic myometrial contraction s are generated by intracellular signaling mechanisms involving activa tion of the phosphatidylinositol-signaling pathway and the production of cytosolic calcium oscillation-like phenomena.