Vascular Mechanism of Action of Endothelin‐1: Effect of Ca2+ Antagonists
Vascular Mechanism of Action of Endothelin‐1: Effect of Ca2+ Antagonists
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内皮素-1 作用的血管机制：Ca2+ 拮抗剂的作用
DOI：
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发表时间：
1989
影响因子：
3
通讯作者：
P. Braquet
中科院分区：
文献类型：
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作者：
Pierre étienne Chabrier;M. Auguet;P. Roubert;M. Lonchampt;V. Gillard;J. Guillon;S. Delaflotte;P. Braquet
在大鼠离体主动脉和培养的大鼠主动脉平滑肌细胞上研究了内皮衍生肽内皮素-1（ET-1）的血管收缩特性。在大鼠离体主动脉中，内皮素-1在无钙介质中诱导缓慢而持续的收缩;钙再灌注后，引起额外的持续收缩。在血管平滑肌细胞中，内皮素-1引起剂量依赖性的Ca 2+内流，不受钙进入阻滞剂（硝苯地平，D 600，或地尔硫卓）。在这些细胞中，[125 I]-内皮素-I结合到特异性的、可饱和的和高亲和力的识别位点（Kd约为10-9 M，Bmax = 52 $2fmol/10 6细胞）。结合是不可逆的，不受钙拮抗剂的影响。这些数据不支持内皮素-1作为电压依赖性Ca 2+通道的内源性激动剂的假设。内皮素-1的作用可以分为两个部分：一个依赖于Ca ~（2+）内流，但对钙拮抗剂不敏感，另一个不依赖于细胞外Ca ~（2+）。内皮素-1的不可逆结合可能反映了细胞膜内配体的内化，导致多个收缩事件。
Summary The vasoconstrictive properties of the endothelium-derived peptide, endothelin-1 (ET-1), were investigated on rat isolated aorta and on cultured rat aortic smooth muscle cells. In rat isolated aorta, endothelin-1 induced a slow and sustained contraction in a Ca2+-free medium; after calcium readmission, an additional sustained contraction was elicited. In vascular smooth muscle cells, endothelin-1 provoked a dose-dependent Ca2+ influx that was not inhibited by calcium entry blockers (nifedipine, D 600, or diltiazem). In these cells, [125I]-endothelin-l bound to a specific, saturable, and high affinity recognition site (Kd about 10–9 M and Bmax = 52 $$ 2 fmol/106 cells). The binding was not reversible and not affected by calcium antagonists. These data do not support the hypothesis that endothelin-1 acts as an endogenous agonist of the voltage-dependent Ca2+ channels. The action of endothelin-1 can be separated into two components: one dependent on Ca2+ influx but insensitive to calcium antagonists and another independent of extracellular Ca2+. The irreversible binding of endothelin-1 may reflect an internalization of the ligand inside the cell membrane, leading to multiple contractile events.