Word R A, Kamm K E, Stull J T, Casey M L
Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas 75235-9051.
Am J Obstet Gynecol. 1990 Apr;162(4):1103-8. doi: 10.1016/0002-9378(90)91324-6.
Endothelin, a recently discovered sarafotoxin-like peptide secreted by endothelial cells, is a potent stimulator of vascular smooth muscle contraction. We found that the action of endothelin is not restricted to the vasculature; we demonstrated that endothelin causes an increase in the concentration of intracellular Ca++ and phosphorylation of the 20 kd light chain of myosin in human uterine smooth muscle cells in culture. In the absence of Ca++ in the buffer medium of myometrial cells, the effects of endothelin on intracellular Ca++ and myosin light chain phosphorylation are attenuated but not abolished. Endothelin also increases the frequency of contraction of human uterine smooth muscle (longitudinal and circular). The contractile effects of endothelin on myometrial strips are diminished in the presence of nifedipine. We conclude that (1) human myometrium is responsive to endothelin, (2) endothelin promotes contraction in myometrium by effecting an increase in intracellular Ca++ and thus an increase in myosin light chain phosphorylation, and (3) endothelin acts in myometrium by stimulating Ca++ influx as well as Ca++ release from intracellular stores.
内皮素是一种最近发现的由内皮细胞分泌的类铃蟾肽样肽,是血管平滑肌收缩的强效刺激剂。我们发现内皮素的作用并不局限于血管系统;我们证明内皮素可使培养的人子宫平滑肌细胞内的钙离子浓度升高,并使肌球蛋白20kd轻链发生磷酸化。在子宫肌层细胞的缓冲培养基中缺乏钙离子时,内皮素对细胞内钙离子和肌球蛋白轻链磷酸化的作用减弱但并未消除。内皮素还会增加人子宫平滑肌(纵行和环行)的收缩频率。在硝苯地平存在的情况下,内皮素对子宫肌条的收缩作用减弱。我们得出结论:(1)人子宫肌层对内皮素敏感;(2)内皮素通过增加细胞内钙离子浓度从而增加肌球蛋白轻链磷酸化来促进子宫肌层收缩;(3)内皮素通过刺激钙离子内流以及细胞内钙库释放钙离子而在子宫肌层发挥作用。