THE RELATIONSHIP BETWEEN OXYTOCIN, PHOSPHOINOSITIDE-SPECIFIC PHOSPHOLIPASE-C, AND PHASIC MYOMETRIAL CONTRACTIONS

OBJECTIVES: Oxytocin-stimulated Uterine contractions ave associated with repetitive cycles of elevated cytosolic calcium, ie, cytosolic calcium oscillations. The studies in this report were performed to test the hypothesis that phosphoinositide-specific phospholipase C (PI-PLC) is an important component of the myometrial intracellular oscillator. METHODS: In vitro isometric contraction studies were performed using longitudinal strips of myometrium from nonpregnant, adult Sprague-Dawley vats. Cumulative dose-response studies were performed using oxytocin and aluminum fluoride with and without 2-nitro-4-carboxyphenyl-N-N-phenylcarbamate (NCDC), an inhibitor of PI-PLC. RESULTS: Stimulation of G-proteins coupled to PI-PLC with aluminum fluoride resulted in a significant increase in phasic myometrial contractions comparable to those produced by oxytocin. Inhibition of PI-PLC with NCDC resulted in significant suppression of oxytocin- and aluminum fluoride-stimulated myometrial contractions. In contrast, doses that suppressed agonist-stimulated contractions had only a minimal effect on KCl-stimulated tonic myometrial contractions. CONCLUSIONS: These studies provide significant support for the novel hypothesis that PI-PLC is an important component of the agonist-stimulated cytosolic calcium oscillator that generates phasic myometrial contractions.