The role of phospholipase Cgamma1 tyrosine phosphorylation during phasic myometrial contractions.

Abstract

Phospholipase Cgamma1 (PLCgamma1) is expressed in myometrium and is activated by tyrosine phosphorylation. These studies sought to determine the association between PLCgamma1 tyrosine phosphorylation and spontaneous uterine contractions. In vitro contraction studies were performed with spontaneously contracting rat uterine strips along with strips that were treated with potassium bisperoxo(1,10 phenanthroline)oxovanadate (bpV(phen), a protein tyrosine phosphatase inhibitor. Additional studies were performed with phenylarsine oxide (a PLCgamma inhibitor) and other inhibitors. Western blots were performed to determine the phosphotyrosine PLCgamma1 levels. Spontaneous contractile activity and tyrosine phosphorylation of PLCgamma1 (but not PLCgamma2) were increased significantly in response to bpV(phen); in contrast, oxytocin and thrombin produced comparable contractile activity but did not alter phosphotyrosine-PLCgamma1. Phenylarsine oxide and neomycin significantly decrease bpV(phen)-stimulated contractions and PLCgamma1 tyrosine phosphorylation; other inhibitors only suppressed contractions. These studies support the hypothesis that spontaneous myometrial contractions are associated with tyrosine phosphorylation of PLCgamma1; both of which are further enhanced by the inhibition of protein tyrosine phosphatase activity.