The relationship between oxytocin, phosphoinositide-specific phospholipase C, and phasic myometrial contractions.
OBJECTIVE
Oxytocin-stimulated uterine contractions are associated with repetitive cycles of elevated cytosolic calcium, i.e., 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 rats. Cumulative dose-response studies were performed using oxytocin and aluminum fluoride with and without 2-nitro-4-carboxyphenyl-N, N-diphenylcarbamate (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.
Phillippe
M
M
Department of Obstetrics and Gynecology, University of Chicago Hospitals, IL 60637, USA.
D017607:Aluminum Compounds / Q000494:pharmacology; D000818:Animals; D005260:Female; D005459:Fluorides / Q000494:pharmacology; D066298:In Vitro Techniques; D010121:Oxytocin / Q000494:pharmacology*; D010507:Periodicity; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D054801:Phosphoinositide Phospholipase C; D051381:Rats; D017207:Rats, Sprague-Dawley; D010738:Type C Phospholipases / Q000494:pharmacology*; D014590:Uterine Contraction / Q000187:drug effects*
D017607:Aluminum Compounds; D010121:Oxytocin; D010738:Type C Phospholipases; D054801:Phosphoinositide Phospholipase C; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D005459:Fluorides; C032311:aluminum fluoride