Role of protein kinase Cbeta in rhythmic contractions of human pregnant myometrium.
To assess the role of protein kinase Cbeta (PKCbeta) in human myometrial contractions during pregnancy, we evaluated the effect of a PKCbeta inhibitor (LY333531) on the pregnant and nonpregnant myometrial contractions and compared the level of PKCbeta in the pregnant myometrium with that in the nonpregnant myometrium. The effects of LY333531 on the myometrial contractions were examined by measuring contractile activity (frequency and amplitude). PKCbeta in human myometrium was assessed at mRNA level using real-time PCR method. The characteristics of contractile activity were different between the pregnant and the nonpregnant myometrium. The amplitude of rhythmic contractions in the preterm and term myometrium was increased 2- to 2.5-fold when compared with that in the nonpregnant myometrium, but the frequency of rhythmic contractions was decreased by about half. LY333531 (10(-6) M) reduced the increased amplitude in the preterm and term myometrium by about 50%, and the inhibitory effects of LY333531 in the pregnant myometrium were significantly greater than that in the nonpregnant myometrium (about 50 vs 25%). However, the frequency in the pregnant and nonpregnant myometrium was not influenced by LY333531. Real-time PCR revealed a significant, five- to sevenfold increase in the expression of PKCbeta mRNA in the preterm and term myometrium when compared with the nonpregnant myometrium. These findings suggest that the increased amplitude of human myometrial contractions during pregnancy is related to the increased level of PKCbeta. A PKCbeta inhibitor may reduce preterm uterine contractions and prevent preterm delivery.
Yasuda
Katsuhiko
K
Department of Obstetrics and Gynecology, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka 570-8507, Japan. yasuda@takii.kmu.ac.jp
Nakamoto
Tsuyoshi
T
Yasuhara
Masahiro
M
Okada
Hidetaka
H
Nakajima
Tatsuya
T
Kanzaki
Hideharu
H
Hori
Masatoshi
M
Ozaki
Hiroshi
H
D000328:Adult; D002227:Carbazoles / Q000494:pharmacology; D016022:Case-Control Studies; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007743:Labor, Obstetric / Q000502:physiology*; D008301:Maleimides / Q000494:pharmacology; D009215:Myometrium / Q000201:enzymology / Q000502:physiology*; D007752:Obstetric Labor, Premature / Q000201:enzymology; D010120:Oxytocics / Q000494:pharmacology; D010121:Oxytocin / Q000494:pharmacology; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D064546:Protein Kinase C beta; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013268:Stimulation, Chemical; D014590:Uterine Contraction / Q000187:drug effects / Q000502:physiology*
D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D010120:Oxytocics; D012333:RNA, Messenger; C081021:Go 6976; D010121:Oxytocin; C099154:ruboxistaurin; D011493:Protein Kinase C; D064546:Protein Kinase C beta; C064758:Ro 31-8220