Sawada Kenjiro, Morishige Ken-ichirou, Hashimoto Kae, Tasaka Keiichi, Kurachi Hirohisa, Murata Yuji, Kurachi Yoshihisa
Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
Eur J Obstet Gynecol Reprod Biol. 2005 Sep 1;122(1):49-56. doi: 10.1016/j.ejogrb.2004.11.026.
We analyzed the gestational changes of pharmacological activity and molecular levels of KATP channels in rat myometrium.
Using rat myometrium, the effects of K+ channel openers (KCOs) were examined in an isometric tension study of oxytocin-induced contraction. We also examined the effects of KCOs on the intracellular Ca2+ levels of cultured myometrial cells. The expression of myometrial KATP channels was assessed by RT-PCR and Northern blot analysis.
The effect of KCOs were altered during pregnancy, with a significant increase of their potency at day 18 of pregnancy followed by a decline towards the non-pregnant level at the day of delivery. KCOs suppressed the Ca2+ influx across the cell membrane. The mRNAs encoding each component of myometrial KATP channels, Kir6.1 and SUR2B, exhibited gestational stage-dependent alterations similar to those of the effects of KCOs.
These findings suggest that KCOs inhibit uterine myometrial contraction more effectively during pregnancy than in the non-pregnant state due to gestation-enhanced expression of KATP channels, implying that KCOs might be useful for preventing premature delivery.
我们分析了大鼠子宫肌层中KATP通道的药理活性和分子水平的妊娠变化。
使用大鼠子宫肌层，在催产素诱导收缩的等长张力研究中检测钾通道开放剂（KCOs）的作用。我们还检测了KCOs对培养的子宫肌层细胞内钙离子水平的影响。通过逆转录聚合酶链反应（RT-PCR）和Northern印迹分析评估子宫肌层KATP通道的表达。
KCOs的作用在妊娠期间发生改变，在妊娠第18天其效力显著增加，随后在分娩日降至非妊娠水平。KCOs抑制钙离子跨细胞膜内流。编码子宫肌层KATP通道各组分Kir6.1和SUR2B的信使核糖核酸（mRNAs）表现出与KCOs作用相似的妊娠阶段依赖性改变。
这些发现表明，由于妊娠期间KATP通道表达增强，KCOs在妊娠期间比在非妊娠状态下更有效地抑制子宫肌层收缩，这意味着KCOs可能对预防早产有用。
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