N'Diaye N, Pueyo M E, Battle T, Ossart C, Guédin D, Michel J B
INSERM U460, Faculté de Médecine Xavier Bichat, Paris, France.
Eur J Pharmacol. 1997 Mar 5;321(3):387-96. doi: 10.1016/s0014-2999(96)00973-9.
Functional conversion of big-endothelin-1 to endothelin-1 and characterization of endothelin receptor subtype were investigated in cultured rat aortic endothelial cells. Exogenous endothelin-1 and big-endothelin-1 both increased arachidonic acid release and inositol phosphate production dose dependently. Endothelin-1 was more potent than big-endothelin-1 as indicated by EC50 values: 0.5 +/- 0.1 nM and 10.0 +/- 2.0 nM for endothelin-1-induced arachidonic acid release and inositol phosphate formation, respectively, versus 1.0 +/- 0.4 nM and 35.0 +/- 6.0 nM for big-endothelin-1-induced responses. Big-endothelin-1, but not endothelin-1 actions were inhibited by phosphoramidon. Comparative studies of endothelin receptor agonists and antagonists showed that endothelin-3 but not sarafotoxin S6c stimulated arachidonic acid release and inositol phosphate formation. The responses to big-endothelin-1 and endothelin-1 were specifically inhibited by the selective endothelin ETA receptor antagonist, [cyclo-D-Trp-D-Asp-Pro-D-Val-Leu] (BQ-123) but not by the selective endothelin ETB receptor antagonist [N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma- methyl-Leu-D-Trp-(COMe)-D-NLeu-ONa] (BQ-788). [125I]Endothelin-1 binding was inhibited by endothelin-1, endothelin-3 and BQ-123 but not by BQ-788. These results indicate that the pharmacological responses to big-endothelin-1 in aortic endothelial cells are due to the extracellular phosphoramidon-sensitive conversion to endothelin-1. Endothelin effects are mediated through endothelin ETA receptors in these cells.
在培养的大鼠主动脉内皮细胞中研究了大内皮素 -1 向内皮素 -1 的功能转化及内皮素受体亚型的特性。外源性内皮素 -1 和大内皮素 -1 均剂量依赖性地增加花生四烯酸释放和肌醇磷酸生成。内皮素 -1 比大内皮素 -1 更有效，如半数有效浓度（EC50）值所示：内皮素 -1 诱导花生四烯酸释放和肌醇磷酸生成的 EC50 值分别为 0.5±0.1 nM 和 10.0±2.0 nM，而大内皮素 -1 诱导反应的 EC50 值分别为 1.0±0.4 nM 和 35.0±6.0 nM。大内皮素 -1 的作用而非内皮素 -1 的作用被磷酰胺素抑制。内皮素受体激动剂和拮抗剂的比较研究表明，内皮素 -3 而非 Sarafotoxin S6c 刺激花生四烯酸释放和肌醇磷酸生成。对大内皮素 -1 和内皮素 -1 的反应被选择性内皮素 ETA 受体拮抗剂[环 -D -Trp -D -Asp -Pro -D -Val -Leu]（BQ -123）特异性抑制，但未被选择性内皮素 ETB 受体拮抗剂[N -顺式 -2,6 -二甲基哌啶羰基 -L -γ -甲基 -Leu -D -Trp -（COMe）-D -NLeu -ONa]（BQ -788）抑制。[125I]内皮素 -1 结合被内皮素 -1、内皮素 -3 和 BQ -123 抑制，但未被 BQ -788 抑制。这些结果表明，主动脉内皮细胞中对大内皮素 -1 的药理反应归因于细胞外磷酰胺素敏感的转化为内皮素 -1。内皮素的作用在这些细胞中通过内皮素 ETA 受体介导。
