Oxytocin stimulates mitogen-activated protein kinase activity in cultured human puerperal uterine myometrial cells.
The regulation of mitogen-activated protein (MAP) kinase by oxytocin in cultured human uterine myometrial cells was investigated. Oxytocin caused the rapid stimulation of MAP kinase activity detected in 32P incorporation of MAP-2. Oxytocin also stimulated the phosphorylation of MAP kinase detected in incorporation of [32P]orthophosphate into MAP kinase. Furthermore, oxytocin induced the tyrosine phosphorylation of MAP kinase. The oxytocin-dependent increase in the tyrosine phosphorylation of MAP kinase displayed a transient time course and was dependent on the concentration of oxytocin applied to the cells. Furthermore, we examined the mechanism by which oxytocin induced MAP kinase phosphorylation. Islet-activating protein (100 ng/ml), which inactivates Gi/Go proteins, blocked the oxytocin-induced phosphorylation of MAP kinase. Moreover, 1 microM ritodrine, which is known to relax uterine muscle contraction, attenuated oxytocin-induced MAP kinase activity and phosphorylation. These results provide evidence that oxytocin acutely activates MAP kinase through an islet-activating protein-sensitive G-protein in human uterine myometrial cells, suggesting that this new pathway may play an important role in the biological action of oxytocin on these cells.
Ohmichi
M
M
Department of Obstetrics and Gynecology, Osaka University Medical School, Japan.
Koike
K
K
Nohara
A
A
Kanda
Y
Y
Sakamoto
Y
Y
Zhang
Z X
ZX
Hirota
K
K
Miyake
A
A
D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000302:isolation & purification / Q000378:metabolism*; D002478:Cells, Cultured; D002585:Cesarean Section; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D006801:Humans; D007700:Kinetics; D009215:Myometrium / Q000187:drug effects / Q000201:enzymology*; D010121:Oxytocin / Q000494:pharmacology*; D010766:Phosphorylation; D019000:Phosphotyrosine; D049590:Postpartum Period / Q000378:metabolism*; D011247:Pregnancy; D012312:Ritodrine / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism
D019000:Phosphotyrosine; D014443:Tyrosine; D010121:Oxytocin; D004815:Epidermal Growth Factor; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D012312:Ritodrine