Vigne P, Marsault R, Breittmayer J P, Frelin C
Institut de Pharmacologie Moléculaire et Cellulaire, UPR 411 CNRS, Valbonne, France.
Biochem J. 1990 Mar 1;266(2):415-20. doi: 10.1042/bj2660415.
Endothelin-1 (ET-1) is a novel vasoconstricting and cardiotonic peptide that is synthesized by the vascular endothelium. Bovine aortic endothelial cells which secrete ET in vitro lack membrane receptor sites for the peptide. Endothelial cells from rat brain microvessels that do not secrete ET in vitro express large amounts of high-affinity receptors for 125I-labelled ET-1 (Kd 0.8 nM). The ET receptor is recognized by sarafotoxin S6b and the different ET peptides with the following order of potency: ET-1 (Kd 0.5 nM) approximately equal to ET-2 (Kd 0.7 nM) greater than sarafotoxin S6b (Kd 27 nM) greater than ET-3 (Kd 450 nM). This structure-activity relationship is different from those found in vascular smooth muscle cells, renal cells and cardiac cells. ET-1 stimulates DNA synthesis in brain capillary endothelial cells. It is more potent than basic fibroblast growth factor. The action of ET on endothelial cells from microvessels involves phosphatidylinositol hydrolysis and intracellular Ca2+ mobilization. These observations suggest that brain endothelial cells might be an important target for ET.
内皮素 -1（ET -1）是一种由血管内皮合成的新型血管收缩和强心肽。体外分泌ET的牛主动脉内皮细胞缺乏该肽的膜受体位点。体外不分泌ET的大鼠脑微血管内皮细胞表达大量针对125I标记的ET -1的高亲和力受体（解离常数Kd为0.8 nM）。ET受体可被沙罗毒素S6b和不同的ET肽识别，其效力顺序如下：ET -1（Kd为0.5 nM）约等于ET -2（Kd为0.7 nM）大于沙罗毒素S6b（Kd为27 nM）大于ET -3（Kd为450 nM）。这种构效关系与在血管平滑肌细胞、肾细胞和心肌细胞中发现的不同。ET -1刺激脑毛细血管内皮细胞中的DNA合成。它比碱性成纤维细胞生长因子更有效。ET对微血管内皮细胞的作用涉及磷脂酰肌醇水解和细胞内Ca2 +动员。这些观察结果表明脑内皮细胞可能是ET的重要靶标。
