Télémaque S, Gratton J P, Claing A, D'Orléans-Juste P
Department of Pharmacology, Medical School, Université de Sherbrooke, Québec, Canada.
J Cardiovasc Pharmacol. 1993;22 Suppl 8:S85-9. doi: 10.1097/00005344-199322008-00024.
The pharmacology of human big endothelin-1 (big ET-1) and big ET-3 was compared in five pharmacologic models: perfused rat and guinea pig lungs, perfused rabbit kidney, and in the rat and the guinea pig in vivo (blood pressure monitoring). In these models, big ET-1 consistently induced concentration- or dose-dependent pharmacologic effects sensitive to phosphoramidon (vasopressor or prostanoid-releasing effects). In contrast, big ET-3, dissolved in either phosphate-buffered saline (pH 7.4) or 0.1% acetic acid, was inactive in all the models used in this study. In addition, the activity of big ET-3 was also assessed in the prostatic portion of the rat vas deferens. In this model, although big ET-1 induced a phosphoramidon-sensitive increase of the twitch response of the tissue to electrical stimulation, big ET-3, dissolved either in phosphate-buffered saline or acetic acid, remained inactive. Our results, presented in the above-mentioned models, illustrate the capacity of the phosphoramidon-sensitive endothelin-converting enzyme (ECE) to discriminate between human big ET-1 and big ET-3.
在五个药理学模型中比较了人 big 内皮素 -1（big ET-1）和 big 内皮素 -3（big ET-3）的药理学特性：灌注大鼠和豚鼠肺、灌注兔肾，以及大鼠和豚鼠体内（血压监测）。在这些模型中，big ET-1 始终诱导出对磷酰胺敏感的浓度或剂量依赖性药理作用（升压或前列腺素释放作用）。相比之下，溶解于磷酸盐缓冲盐水（pH 7.4）或 0.1%乙酸中的 big ET-3 在本研究使用的所有模型中均无活性。此外，还在大鼠输精管的前列腺部分评估了 big ET-3 的活性。在该模型中，尽管 big ET-1 诱导组织对电刺激的抽搐反应出现磷酰胺敏感的增加，但溶解于磷酸盐缓冲盐水或乙酸中的 big ET-3 仍然无活性。我们在上述模型中呈现的结果表明，磷酰胺敏感的内皮素转换酶（ECE）能够区分人 big ET-1 和 big ET-3。
