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Center for Perinatal Biology, Department of Pharmacology, Loma Linda University School of Medicine, Loma Linda, California 92350
The present study investigated the
potential role of extracellular signal-regulated kinase (ERK) in
uterine artery contraction and tested the hypothesis that pregnancy
upregulated ERK-mediated function in the uterine artery. Isometric
tension in response to phenylephrine (PE), serotonin (5-HT), phorbol
12,13-dibutyrate (PDBu), and KCl was measured in the ring preparation
of uterine arteries obtained from nonpregnant and near-term (140 days
gestation) pregnant sheep. Inhibiting ERK activation with PD-98059 did
not change the KCl-evoked contraction but significantly inhibited the contraction to 5-HT in both nonpregnant and pregnant uterine arteries. PD-98059 did not affect PE-induced contraction in the uterine
arteries of nonpregnant sheep but significantly decreased it in the
uterine arteries of pregnant sheep. In accordance, PE stimulated
activation of ERK in uterine arteries of pregnant sheep, which was
blocked by PD-98059. PD-98059-mediated inhibition of the PE-induced
contraction was associated with a decrease in both intracellular
Ca2+ concentration and Ca2+ sensitivity of
contractile proteins in the uterine arteries of pregnant sheep.
PDBu-mediated contraction was significantly less in pregnant than in
nonpregnant uterine arteries. PD-98059 had no effect on PDBu-induced
contraction in nonpregnant but significantly increased it in pregnant
uterine arteries. In addition, PD-98059 significantly enhanced
PDBu-stimulated protein kinase C activity. The results indicate that
ERK plays an important role in the regulation of uterine artery
contractility, and its effect is agonist dependent. More importantly,
pregnancy selectively enhances the role of ERK in
1-adrenoceptor-mediated contractions and its effect in
suppressing protein kinase C-mediated contraction in the uterine artery.
mitogen-activated protein kinase; PD-98059; calcium; protein kinase
C; 1-adrenoceptor; extracellular signal-regulated kinase
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