Mark Phillippe1, Leigh M Sweet, Daniel Engle. 1. Department of Obstetrics and Gynecology, University of Vermont College of Medicine, Burlington, VT 05405, USA. Mark.Phillippe@uvm.edu
Abstract
OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSION: 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.
OBJECTIVE:Phospholipase Cgamma1 (PLCgamma1) is expressed in myometrium and is activated by tyrosine phosphorylation. These studies sought to determine the association between PLCgamma1tyrosine phosphorylation and spontaneous uterine contractions. STUDY DESIGN: 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 phosphotyrosinePLCgamma1 levels. RESULTS: 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 PLCgamma1tyrosine phosphorylation; other inhibitors only suppressed contractions. CONCLUSION: 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.