Clozel M, Fischli W, Guilly C
Pharmaceutical Research Department, F. Hoffmann-La Roche & Co., Ltd., Basle, Switzerland.
J Clin Invest. 1989 May;83(5):1758-61. doi: 10.1172/JCI114078.
Endothelin is a newly discovered, potent vasoconstrictor peptide secreted by endothelial cells. The binding of endothelin was studied on cultured human vascular smooth muscle cells obtained from umbilical veins. A single specific binding site for 125I-endothelin was identified, with an apparent Kd of 126 pM and a maximal binding capacity of approximately 10,000 sites per smooth muscle cell. At room temperature the binding was saturable, reached equilibrium at 2 h (using 20 pM endothelin), and was slowly and only partially reversed by unlabeled endothelin. The calcium antagonists nifedipine, nicardipine, and diltiazem did not compete for the same binding site. Conditioned medium from cultured human umbilical vein endothelial cells inhibited the binding of 125I-endothelin dose dependently. This effect was antagonized by anti-endothelin antiserum. We conclude that human umbilical vein smooth muscle cells possess specific binding sites for endothelin, and that human endothelial cells secrete an endothelinlike material.
内皮素是一种新发现的、由内皮细胞分泌的强效血管收缩肽。对从脐静脉获取的培养人血管平滑肌细胞上内皮素的结合情况进行了研究。确定了一个针对125I - 内皮素的单一特异性结合位点,其表观解离常数(Kd)为126皮摩尔,每个平滑肌细胞的最大结合容量约为10,000个位点。在室温下,结合是可饱和的,在2小时(使用20皮摩尔内皮素)时达到平衡,且未标记的内皮素只能缓慢且部分逆转这种结合。钙拮抗剂硝苯地平、尼卡地平及地尔硫䓬并不竞争相同的结合位点。培养的人脐静脉内皮细胞的条件培养基能剂量依赖性地抑制125I - 内皮素的结合。这种效应可被抗内皮素抗血清所拮抗。我们得出结论,人脐静脉平滑肌细胞具有内皮素的特异性结合位点,并且人内皮细胞分泌一种类内皮素物质。