Tyrosine kinase-mediated activation of cytosolic calcium oscillations and phasic myometrial contractions

These studies sought to test the hypothesis that tyrosine kinase-stimulated phasic myometrial contractions are mediated by activation of the phosphati dylinositol (PI)-signaling pathway and the generation of cytosolic calcium oscillations. For these studies, uterine tissue was obtained from adult fem ale Sprague-Dawley white rats during the proestrus/estrus phase of the cycl e. In vitro contraction studies were performed using pervanadate (a tyrosin e phosphatase inhibitor) with and without inhibitors of the PI-signaling pa thway, including 2-nitro-4-carboxyphenyl- N,N-diphenylcarbamate (a phosphol ipase C inhibitor), thimerosal (an inositol-trisphosphate receptor/channel inhibitor), and Ruthenium red (a ryanodine receptor), and with oxytocin or prostaglandin F2 alpha (two classic utreotonic agonists). cytosolic calcium studies were performed using Fura-2-loaded myometrial strips. during these studies, prevanadate was observed to produce cytosolic calcium oscillation s and prostaglandin F2 alpha. The pervanadate-stimulated phasic contraction s were significantly suppressed in response to inhibition of phospholipase C, the inositol-trisphosphate receptor, and the ryanodine receptor, thereby confirming the importance of the PI-signaling pathway during tyrosine kina se-associated myometrial activity. Further confirming the important and sha red role of the PI-signaling pathway during pervandate-stimulated myometria l contractions, no significant additive effects were observed when classic uterotonic agonists such as oxytocin or prostaglandin F2 alpha were obtaine d with pervanadate. Copyright (C) 1999 bt the Society for Gynecologic Inves tigation.