Hopkins N K, Gorman R R
J Clin Invest. 1981 Feb;67(2):540-6. doi: 10.1172/JCI110064.
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.
对培养的人脐静脉内皮细胞中前列腺素刺激的腺苷3',5'-环磷酸单磷酸（环磷酸腺苷）积累的分析表明，前列环素（PGI2）是最有效的激动剂，其次是前列腺素（PG）H2，其比PGE2更有效，而PGD2基本无活性。所研究的内皮细胞显然具有较高的环磷酸腺苷磷酸二酯酶活性，因为在存在磷酸二酯酶抑制剂异丁基甲基黄嘌呤（MIX）的情况下，未显示出PGI2介导的环磷酸腺苷有显著增加。前列腺素内过氧化物PGH2刺激的环磷酸腺苷积累被前列环素合成酶抑制剂12-氢过氧二十碳四烯酸或9,11-偶氮前列腺素-5,13-二烯酸抑制75%-80%。这些数据表明，PGH2刺激主要是由于转化为PGI2。β-肾上腺素能激动剂L-异丙肾上腺素刺激内皮细胞中环磷酸腺苷的积累。这种积累被普萘洛尔完全阻断。然而，β-肾上腺素能药物刺激的环磷酸腺苷积累不如PGI2诱导的积累。此外，PGI2反应不能被普萘洛尔阻断。在存在MIX的情况下，凝血酶刺激的PGI2生物合成被PGE1或异丙肾上腺素减弱。单独的MIX不如PGE1或异丙肾上腺素加MIX的组合有效。这些数据表明内皮细胞合成PGI2有两个潜在作用：第一，PGI2可提高血小板中的环磷酸腺苷，第二，内皮细胞中的环磷酸腺苷也可提高，从而使随后的PGI2合成减弱。
