Shirotani M, Yui Y, Hattori R, Kawai C
Department of Internal Medicine, Faculty of Medicine, Kyoto University, Japan.
Prostaglandins. 1991 Feb;41(2):97-110. doi: 10.1016/0090-6980(91)90023-9.
The effects of U-61,431F, ciprostene, a stable prostacyclin analogue, were examined on the proliferation of cultured quiescent bovine aortic endothelial cells (EC) and smooth muscle cells (SMC). After stimulation with 5% fetal calf serum, U-61,431F suppressed both the DNA synthesis and proliferation of SMC dose-dependently at the concentration of 3-100 microM, but had no effect on either of them in EC at a concentration of up to 30 microM. The inhibitory effect on DNA synthesis was greater in SMC than in EC at 3-50 microM. When SMC were stimulated with platelet-derived growth factor (PDGF) for 2 hrs followed by a 22-hr incubation with insulin, U-61,431F (1-50 microM) administered at the time of PDGF stimulation did not inhibit DNA synthesis. SMC initiated and terminated DNA synthesis at about 15-18 h and 24 h after stimulation with serum, respectively. Inhibition of DNA synthesis in serum-stimulated SMC as a function of the addition time of U-61,431F reduced at 3-12 h after the stimulation. U-61,431F raised the cyclic AMP (cAMP) content in SMC. Moreover, a phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, and a more specific cAMP phosphodiesterase inhibitor, Ro 20-1724, augmented the inhibition of DNA synthesis in SMC concomitant with further elevation of cAMP level. These results suggest that U-61,431F inhibits DNA synthesis of SMC acting in the progression stage rather than in the competence stage, with little antiproliferative effect on EC. cAMP may play an important role in its antiproliferative action in SMC.
研究了稳定的前列环素类似物U-61,431F、西前列烯对培养的静止牛主动脉内皮细胞（EC）和平滑肌细胞（SMC）增殖的影响。用5%胎牛血清刺激后，U-61,431F在3 - 100微摩尔浓度下剂量依赖性地抑制SMC的DNA合成和增殖，但在浓度高达30微摩尔时对EC的这两者均无影响。在3 - 50微摩尔时，对SMC的DNA合成抑制作用比对EC更强。当用血小板衍生生长因子（PDGF）刺激SMC 2小时，随后与胰岛素孵育22小时时，在PDGF刺激时给予的U-61,431F（1 - 50微摩尔）不抑制DNA合成。血清刺激后，SMC分别在约15 - 18小时和24小时开始并终止DNA合成。U-61,431F添加时间对血清刺激的SMC中DNA合成的抑制作用在刺激后3 - 12小时减弱。U-61,431F提高了SMC中的环磷酸腺苷（cAMP）含量。此外，磷酸二酯酶抑制剂3 - 异丁基 - 1 - 甲基黄嘌呤和更特异的cAMP磷酸二酯酶抑制剂Ro 20 - 1724增强了对SMC中DNA合成的抑制作用，同时cAMP水平进一步升高。这些结果表明，U-61,431F抑制处于进展期而非感受态期的SMC的DNA合成，对EC几乎没有抗增殖作用。cAMP可能在其对SMC的抗增殖作用中起重要作用。
