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Role of protein kinase Cß in rhythmic contractions of human pregnant myometrium

Department of Obstetrics and Gynecology, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka 570-8507, Japan and ¹ Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Bunkyo-ku, Yayoi 1-1-1, Tokyo 113-8657, Japan

Correspondence should be addressed to K Yasuda; Email: yasuda{at}takii.kmu.ac.jp

To assess the role of protein kinase Cß (PKCß) in human myometrial contractions during pregnancy, we evaluated the effect of a PKCß inhibitor (LY333531) on the pregnant and nonpregnant myometrial contractions and compared the level of PKCß 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). PKCß 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 PKCß 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 PKCß. A PKCß inhibitor may reduce preterm uterine contractions and prevent preterm delivery.