Deschepper C F, Houweling A D, Picard S
MRC Multidisciplinary Research Group on Hypertension, Institut de Recherches Cliniques de Montréal (IRCM), Québec, Canada.
Eur J Pharmacol. 1995 Feb 24;275(1):61-6. doi: 10.1016/0014-2999(94)00746-t.
Both endothelins and their big-endothelin precursors were found capable of inducing the release of arachidonic acid from purified cultures of rat astrocytes. Their order of potency was as follows: big-endothelin-3 < big-endothelin-1 < endothelin-1 = endothelin-3. Mature endothelins induced the release of arachidonic acid in a rapid fashion. In contrast, much longer incubation times were required for big-endothelins to exert an effect, suggesting that their activity was dependent on their conversion. When big-endothelin-1 was added to the incubation medium of intact live astrocytes, it was converted into mature endothelin-1 in a time-dependent manner and the conversion was inhibited by phosphoramidon. This suggests that astrocytic endothelin-converting enzyme is (at least in part) an external membrane-bound metalloprotease. Some conversion of big-endothelin-3 into endothelin-3 also occurred. However, it was less efficient than the conversion of big-endothelin-1, which is compatible with the lower bioactivity of big-endothelin-3 vs. that of big-endothelin-1 in astrocytes.
在内皮素及其大内皮素前体均被发现能够诱导从大鼠星形胶质细胞的纯化培养物中释放花生四烯酸。它们的效力顺序如下：大内皮素-3 < 大内皮素-1 < 内皮素-1 = 内皮素-3。成熟内皮素能迅速诱导花生四烯酸的释放。相比之下，大内皮素发挥作用需要更长的孵育时间，这表明它们的活性依赖于其转化。当将大内皮素-1添加到完整活星形胶质细胞的孵育培养基中时，它会以时间依赖性方式转化为成熟内皮素-1，并且这种转化受到磷酰胺素的抑制。这表明星形胶质细胞内皮素转化酶（至少部分）是一种外膜结合金属蛋白酶。大内皮素-3也会部分转化为内皮素-3。然而，其效率低于大内皮素-1的转化，这与大内皮素-3在星形胶质细胞中相对于大内皮素-1较低的生物活性相符。
