Moore J J, Dubyak G R, Moore R M, Vander Kooy D
Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44109.
Endocrinology. 1988 Oct;123(4):1771-7. doi: 10.1210/endo-123-4-1771.
It has been postulated that fetal hormonal signals act upon amnion to trigger labor via prostaglandin (PG) production. Human amnion epithelial cell cultures were established to test the effects of potential activators of the inositol phospholipid-protein kinase-C effector system on intracellular inositol phosphate turnover, intracellular free calcium ([ Ca2+]i), and PGE2 production. Oxytocin provoked 3-, 2.5-, and 4-fold increases in inositol triphosphate, inositol bisphosphate, and inositol monophosphate, respectively. [Ca2+]i, measured with the fluorescent dye fura-2, was stimulated by oxytocin and vasopressin (oxytocin greater than vasopressin) in a dose-dependent manner. The [Ca2+]i transient produced by oxytocin reached a peak in 15 sec, followed by a slow return to baseline over 10 min. Preincubation with phorbol 12-myristate-13 acetate (PMA) markedly blunted the oxytocin-induced transient. No [Ca2+]i transient was seen with leukotrienes, PG, serotonin, angiotensin, or alpha- or beta-adrenergic agents. PGE2 production increased 30- to 50-fold with phospholipase-C and PMA, and 10-fold with the calcium ionophore A23187. Oxytocin and vasopressin produced 10- and 3-fold PGE2 increases, respectively. Increased PGE2 production induced by PMA, oxytocin, and A23187 was first seen after 8 hr of incubation and reached maximal levels at 24 h. Minimal PGE2 stimulation occurred with agents that produced no [Ca2+]i transient. Direct activators of the inositol phospholipid-protein kinase-C system in human amnion induce large increases in PGE2 in human amnion cells. Oxytocin and vasopressin are hormonal activators of this system in these cells, as demonstrated by their effects on inositol phosphate turnover and [Ca2+]i. These hormones also increase PGE2 production and may influence labor by stimulating PGE2 production in amnion through the inositol phospholipid-protein kinase-C system.
据推测，胎儿激素信号作用于羊膜，通过前列腺素（PG）生成来触发分娩。建立人羊膜上皮细胞培养体系，以测试肌醇磷脂 - 蛋白激酶 - C效应系统的潜在激活剂对细胞内肌醇磷酸周转、细胞内游离钙（[Ca2+]i）和前列腺素E2（PGE2）生成的影响。催产素分别使肌醇三磷酸、肌醇二磷酸和肌醇一磷酸增加了3倍、2.5倍和4倍。用荧光染料fura - 2测量的[Ca2+]i受到催产素和血管加压素（催产素作用大于血管加压素）的剂量依赖性刺激。催产素产生的[Ca2+]i瞬变在15秒内达到峰值，随后在10分钟内缓慢恢复到基线水平。用佛波醇12 - 肉豆蔻酸酯 - 13 - 乙酸酯（PMA）预孵育可显著减弱催产素诱导的瞬变。白三烯、PG、5 - 羟色胺、血管紧张素或α - 或β - 肾上腺素能药物未观察到[Ca2+]i瞬变。磷脂酶 - C和PMA使PGE2生成增加30至50倍，钙离子载体A23187使其增加10倍。催产素和血管加压素分别使PGE2增加10倍和3倍。PMA、催产素和A23187诱导的PGE2生成增加在孵育8小时后首次出现，并在24小时达到最高水平。未产生[Ca2+]i瞬变的药物对PGE2的刺激最小。人羊膜中肌醇磷脂 - 蛋白激酶 - C系统的直接激活剂可诱导人羊膜细胞中PGE2大幅增加。催产素和血管加压素是该系统在这些细胞中的激素激活剂，这可通过它们对肌醇磷酸周转和[Ca2+]i的作用得到证明。这些激素还可增加PGE2生成，并可能通过肌醇磷脂 - 蛋白激酶 - C系统刺激羊膜中PGE2生成来影响分娩。
