Kallikrein stimulates prostacyclin production in bovine vascular endothelial cells.
Kallikrein stimulates prostacyclin production in bovine vascular endothelial cells.
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激肽释放酶刺激牛血管内皮细胞中前列环素的产生。
DOI：
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发表时间：
1984
期刊：
影响因子：
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通讯作者：
S. Murota
中科院分区：
文献类型：
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作者：
I. Morita;T. Kanayasu;S. Murota
从牛颈动脉主动脉分离培养的内皮细胞产生前列环素（前列腺素I2）和少量前列腺素E2。采用放射免疫分析技术研究了激肽释放酶（EC 3.4.21.8）对细胞释放前列环素的影响。激肽释放酶以剂量依赖性方式刺激前列环素的释放。 0.1微克/毫升激肽释放酶的最大刺激达到9.2倍。该作用与脂肪酸环加氧酶的激活无关，而是与刺激花生四烯酸的释放有关。但激肽释放酶本身不具有磷脂酶活性。另一方面，在相同剂量下，激肽释放酶不能诱导血小板聚集或增强胶原诱导的血小板聚集。我们的研究结果表明激肽释放酶的血管舒张作用部分是由前列环素的产生介导的。此外，我们研究了激肽释放酶对内皮细胞中前列环素产生的刺激作用与激肽形成相关的可能性。缓激肽和赖氨缓激肽（激肽）也能刺激前列环素的释放，但其效果远不如激肽释放酶。并且添加激肽释放酶和缓激肽对前列环素和花生四烯酸释放的刺激不是竞争性或相加性的，而是协同性的。而且，即使将胎牛血清与激肽释放酶一起孵育，也根本检测不到缓激肽。当激肽释放酶与激肽释放酶的灭活剂阿帕罗丁预孵育时，激肽释放酶的作用被完全消除。这些发现表明，激肽释放酶对血管细胞释放前列环素的刺激作用可能不是由于激肽的形成，而是由于该丝氨酸蛋白酶产生的其他物质。
Cultured endothelial cells isolated from bovine carotid aorta produce prostacyclin (prostaglandin I2) and a small amount of prostaglandin E2. The effects of kallikrein (EC 3.4.21.8) on the release of prostacyclin from the cells were studied with the radioimmunoassay technique. Kallikrein stimulated the release of prostacyclin in a dose-dependent manner. The maximal stimulation reached up to 9.2-fold at 0.1 micrograms/ml of kallikrein. The effect was not associated with the activation of the fatty acid cyclooxygenase, but with the stimulation of arachidonic acid release. But kallikrein itself did not have phospholipase activity. On the other hand, at the same doses, kallikrein failed to induce platelet aggregation or enhance platelet aggregation induced by collagen. Our findings suggest that the vasodilator effect of kallikrein is mediated in part by prostacyclin production. Furthermore, we investigated the possibility that the stimulatory effect of kallikrein on prostacyclin production in endothelial cells is associated with kinin formation. Bradykinin and lysylbradykinin (kallidin) also stimulated the release of prostacyclin, but the effects were far less than that of kallikrein. And the stimulation due to the addition of both kallikrein and bradykinin on prostacyclin and arachidonic acid release was not competitive or additive, but synergistic. Moreover, even if fetal calf serum was incubated with kallikrein, bradykinin was not detected at all. When kallikrein was pre-incubated with aporotinin, which is an inactivator of kallikrein, the effect of kallikrein was completely abolished. These findings suggest that the stimulatory effect of kallikrein on the release of prostacyclin from vascular cells is possibly not due to kinin formation, but to other substance(s) produced by this serine proteinase.