Protein kinase C, an inhibitor of oxytocin-stimulated phasic myometrial contractions.
One of the roles previously reported for protein kinase C (PKC) is modulation of the activity of the phosphatidylinositol signaling pathway. Studies were performed to test the hypothesis that activation of PKC results in inhibition of agonist-stimulated phasic myometrial contractions: contractions that appear to be mediated by phosphatidylinositol signaling mechanisms comparable to those producing cytosolic calcium oscillations. In vitro isometric contraction studies were performed using myometrium from adult Sprague-Dawley rats. Oxytocin and aluminium fluoride (a G-protein activator) produced comparable increases in phasic contractile activity. Phorbol 12,13-dibutyrate (PDB) significantly suppressed agonist-stimulated phasic myometrial contractions; in contrast, phorbol 13,20-diacetate (PDA), an inactive phorbol ester, had no significant effect on myometrial contractions. Prolonged exposure of myometrial tissue to PDB failed to down-regulate myometrial PKC and had no consistent effect on spontaneous and oxytocin-stimulated phasic contractions. These studies have provided support for a role for PKC as an intracellular regulator of the phosphatidylinositol signaling pathway, which itself appears to be part of the myometrial calcium oscillator that results in agonist-stimulated phasic myometrial contractions.
Phillippe
M
M
Department of Obstetrics & Gynecology, University of Chicago, Illinois 60637.
D017607:Aluminum Compounds / Q000494:pharmacology; D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005459:Fluorides / Q000494:pharmacology; D009215:Myometrium / Q000187:drug effects / Q000502:physiology*; D010121:Oxytocin / Q000494:pharmacology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014590:Uterine Contraction / Q000187:drug effects*
D017607:Aluminum Compounds; D010716:Phosphatidylinositols; D015240:Phorbol 12,13-Dibutyrate; D010121:Oxytocin; D011493:Protein Kinase C; D005459:Fluorides; C032311:aluminum fluoride