Stimulation of endothelial cell prostacyclin production by thrombin, trypsin, and the ionophore A 23187.
Stimulation of endothelial cell prostacyclin production by thrombin, trypsin, and the ionophore A 23187.
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凝血酶、胰蛋白酶和离子载体 A 23187 刺激内皮细胞产生前列环素。
DOI：
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发表时间：
1978
影响因子：
15.9
通讯作者：
E. Jaffe
中科院分区：
文献类型：
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作者：
B. Weksler;C. W. Ley;E. Jaffe
前列环素（PGI(2)）是一种不稳定的前列腺素，可抑制血小板聚集和血清素释放，引起血管舒张。培养的人内皮细胞和成纤维细胞单层所产生的PGI(2)活性是通过它们的上清抑制富血小板血浆中血小板聚集的能力，或抑制经阿司匹林处理的洗涤血小板悬浮液中凝血素诱导的[(14)C]血清素释放的能力来测量的。用花生四烯酸钠、凝血酶、离子载体a23187或胰蛋白酶刺激培养的单层人内皮细胞，分泌PGI(2)到上清培养基中。单层成纤维细胞仅在花生四烯酸刺激下产生PGI(2)活性。“静息”时，完整的单层膜不能产生可检测的PGI(2)，用ADP或肾上腺素处理的单层膜也不能。用吲哚美辛、丙氨嘧啶或15-氢过氧花生四烯酸处理单层膜可消除PGI(2)活性的产生。上清液的PGI(2)活性被煮沸或酸化破坏。用氟磷酸二异丙基抑制凝血酶，用大豆胰蛋白酶抑制剂抑制胰蛋白酶，消除了这些酶对PGI(2)产生的刺激。在血管损伤部位产生凝血酶，可以通过刺激损伤区域附近内皮细胞合成PGI(2)，限制参与初级止血反应的血小板数量，并有助于局部血栓形成。
Prostacyclin (PGI(2)) is an unstable prostaglandin which inhibits platelet aggregation and serotonin release and causes vasodilation. The PGI(2) activity produced by monolayers of cultured human endothelial cells and fibroblasts was measured by the ability of their supernates to inhibit platelet aggregation in platelet-rich plasma, or to inhibit thrombin-induced [(14)C]serotonin release from aspirin-treated, washed platelet suspensions. Monolayers of cultured human endothelial cells, stimulated with sodium arachidonate, thrombin, the ionophore A 23187, or trypsin, secreted PGI(2) into the supernatant medium. Monolayers of fibroblasts produced PGI(2) activity only when stimulated by arachidonate. "Resting," intact monolayers did not produce detectable PGI(2), nor did monolayers treated with ADP or epinephrine. Production of PGI(2) activity was abolished by treatment of the monolayers with indomethacin, tranylcypromine, or 15-hydroperoxy arachidonic acid. The PGI(2) activity of the supernates was destroyed by boiling or acidification. Inhibition of thrombin with diisopropylfluoro-phosphate, and of trypsin with soybean trypsin inhibitor, abolished the stimulation of PGI(2) production by these enzymes. Production of thrombin at a site of vascular injury could, by stimulating PGI(2) synthesis by endothelial cells adjacent to the injured area, limit the number of platelets involved in the primary hemostatic response and help to localize thrombus formation.