Role of mitogen-activated protein kinase pathway in prostaglandin F2alpha-induced rat puerperal uterine contraction.
In this study, prostaglandin (PG) F2alpha was found to activate mitogen-activated protein (MAP) kinase and MAP kinase kinase (MEK) in cultured rat puerperal uterine myometrial cells. PGF2alpha stimulation also led to an increase in phosphorylation of raf-1, son of sevenless (SOS), and Shc. Furthermore, we examined the mechanism by which PGF2alpha induced MAP kinase phosphorylation. Both pertussis toxin (10 ng/ml), which inactivates Gi/Go proteins, and expression of a peptide derived from the carboxyl terminus of the beta-adrenergic receptor kinase 1 (betaARK1), which specifically blocks signaling mediated by the betagamma subunits of G proteins, blocked the PGF2alpha-induced activation of MAP kinase. Ritodrine (1 microM), which is known to relax uterine muscle contraction, attenuated PGF2alpha-induced tyrosine phosphorylation of MAP kinase. Moreover, to examine the role of MAP kinase pathway in uterine contraction, an inhibitor of MEK activity, PD098059, was used. Although MEK inhibitor had no effect on PGF2alpha-induced calcium mobilization, this inhibitor partially inhibited PGF2alpha-induced uterine contraction. These results provide evidence that PGF2alpha stimulates the MAP kinase signaling pathway in cultured rat puerperal uterine myometrial cells through Gbetagamma protein, suggesting that this new pathway may play an important role in the biological action of PGF2alpha on these cells.
Ohmichi
M
M
Department of Obstetrics and Gynecology, Osaka University Medical School, Suita-shi, Japan.
Koike
K
K
Kimura
A
A
Masuhara
K
K
Ikegami
H
H
Ikebuchi
Y
Y
Kanzaki
T
T
Touhara
K
K
Sakaue
M
M
Kobayashi
Y
Y
Akabane
M
M
Miyake
A
A
Murata
Y
Y
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D015237:Dinoprost / Q000494:pharmacology*; D004789:Enzyme Activation; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D020929:Mitogen-Activated Protein Kinase Kinases; D009215:Myometrium / Q000166:cytology / Q000201:enzymology; D037342:Pertussis Toxin; D010766:Phosphorylation; D010957:Plasmids; D049590:Postpartum Period / Q000502:physiology*; D011247:Pregnancy; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000032:analysis / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf; D051381:Rats; D017208:Rats, Wistar; D012312:Ritodrine / Q000494:pharmacology; D015149:Tocolytic Agents / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism; D014590:Uterine Contraction / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D005419:Flavonoids; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D015149:Tocolytic Agents; D010566:Virulence Factors, Bordetella; D014443:Tyrosine; D015237:Dinoprost; D037342:Pertussis Toxin; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D012312:Ritodrine; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one