Regulation of endothelial cell cyclic nucleotide metabolism by prostacyclin.
Regulation of endothelial cell cyclic nucleotide metabolism by prostacyclin.
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前列环素调节内皮细胞环核苷酸代谢。
DOI：
10.1172/jci110064
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发表时间：
1981
期刊：
影响因子：
--
通讯作者：
R. Gorman
中科院分区：
文献类型：
--
作者：
N. Hopkins;R. Gorman
在培养的人脐静脉内皮细胞中，一项对前列腺素刺激的环磷酸腺苷（cAMP）积累的分析显示，前列环素（PGI 2）是最有效的激动剂，其次是前列腺素（PG）H2，它比PGE 2更有效，而PGD 2基本上是无活性的。研究的内皮细胞显然有很高的速率环AMP磷酸二酯酶活性，因为显着的PGI 2介导的环AMP的增加不能显示在磷酸二酯酶抑制剂异丁基甲基黄嘌呤（MIX）的存在下。前列环素合成酶抑制剂12-hydroperoxyeicosatetraenoic acid或9，11-azoprosta-5，13-dienoic acid可抑制75- 80%内过氧化物PGH 2刺激环AMP的积累。这些数据表明，PGH 2刺激主要是由于转化为PGI 2。β-肾上腺素能激动剂L-异丙肾上腺素刺激内皮细胞中的环AMP积累。普萘洛尔完全阻断了这种蓄积。然而，刺激环AMP积累的β-肾上腺素能药物不等于PGI 2诱导。此外，PGI 2反应不能被普萘洛尔阻断。凝血酶刺激的PGI 2生物合成减弱PGE 1或异丙肾上腺素在MIX的存在下。单独使用MIX的效果不如PGE 1或异丙肾上腺素加MIX的组合。这些数据表明内皮细胞合成PGI 2的两个潜在作用：第一，PGI 2可以升高血小板中的环AMP，第二，内皮细胞环AMP也可以升高，从而减弱随后的PGI 2合成。
An analysis of prostaglandin-stimulated adenosine 3',5'-cyclic monophosphate (cyclic AMP) accumulation in cultured human umbilical vein endothelial cells showed prostacyclin (PGI2) to be the most potent agonist followed by prostaglandin (PG)H2, which was more potent than PGE2, while PGD2 was essentially inactive. The endothelial cells studied apparently have a high rate of cyclic AMP phosphodiesterase activity because significant PGI2-mediated increases in cyclic AMP could not be shown in the presence of the phosphodiesterase inhibitor isobutylmethylxanthine (MIX). Endoperoxide PGH2-stimulation of cyclic AMP accumulation was inhibited 75--80% by the prostacyclin synthetase inhibitors 12-hydroperoxyeicosatetraenoic acid or 9,11-azoprosta-5,13-dienoic acid. These data indicate that the PGH2-stimulation is due primarily to conversion to PGI2. The beta-adrenergic agonist L-isoproterenol stimulated cyclic AMP accumulation in the endothelial cells. This accumulation was completely blocked by propranolol. However, stimulation of cyclic AMP accumulation by the beta-adrenergic agent did not equal that induced by PGI2. Furthermore, the PGI2 response could not be blocked by propranolol. Thrombin-stimulated PGI2 biosynthesis was attenuated by PGE1 or isoproterenol in the presence of MIX. MIX alone was less effective than a combination of PGE1 or isoproterenol plus MIX. These data suggest two potential effects of PGI2 biosynthesis by endothelial cells: first, the PGI2 can elevate cyclic AMP in platelets, and second, endothelial cell cyclic AMP can be elevated as well, so that subsequent PGI2 synthesis will be attenuated.