Gröne H J, Laue A, Fuchs E
Institut für Pathologie, Universität Göttingen.
Klin Wochenschr. 1990 Aug 2;68(15):758-67. doi: 10.1007/BF01647245.
Endothelins, 21 amino acid peptides, produced by endothelial cells are potent vasoconstrictors and mitogens. According to experimental studies in animals, endothelins seem to be involved in the regulation of renal hemodynamics. In order to gain insight into its potential effects in man, a quantitative analysis of its binding sites was performed in human kidneys. Because of the proliferative action of endothelin in cell culture we also compared binding sites in fetal and adult kidneys. Binding sites for [125I]-endothelin-1,2,3 were visualized by in-vitro autoradiography and quantified by densitometry. In both adult and fetal tissue, specific binding sites occurred in the cortex, medulla, and renal vessels. Unlabeled endothelins and sarafotoxin, a peptide with a high sequence homology to endothelins, inhibited [125I]-endothelin-1 binding with IC50 in the 9.8 to 0.023 nM range, whereas unrelated peptides (angiotensin II, atrial natriuretic peptide) and the calcium antagonist nitrendipine failed to compete for [125I]-endothelin-1 binding sites. Linear Scatchard analysis revealed that the number of binding sites (expressed per tissue equivalent: TE) were consistently higher in fetal than in adult kidneys, while affinities did not differ significantly in cortex, medulla, and vessels (fetal/adult: cortex KD 43.4 +/- 19.6/55.9 +/- 16.7 nM; BMax 13.5 +/- 7.8/2.7 +/- 1.3 fmol/mg TE; medulla KD 26.3 +/- 10.9/34.6 +/- 7.4 nM; BMax 10.1 +/- 0.9/3.7 +/- 1.1 fmol/mg TE; vessels KD 41.1 +/- 22.9/23.7 +/- 8.1 nM; BMax 12.9 +/- 3.9/4.1 +/- 1.2 fmol/mg TE). Medullary capillaries and veins showed strong binding in human and rat kidneys which may be important for the pathophysiology of acute renal failure. Human adult and fetal glomeruli had only a few binding sites. This contrasts to findings in the rat kidney in which glomeruli have a high concentration of endothelin binding sites; although this does not role out an influence per se, it does point out the need to subject the assumption of a relevant glomerular effect of endothelin in man to closer scrutiny. The diffuse and strong binding in fetal kidney may indicate a role for endothelin in the process of renal maturation.
内皮素是由内皮细胞产生的21个氨基酸的肽类，是强效血管收缩剂和有丝分裂原。根据动物实验研究，内皮素似乎参与肾血流动力学的调节。为了深入了解其对人类的潜在影响，对人肾中的内皮素结合位点进行了定量分析。由于内皮素在细胞培养中有增殖作用，我们还比较了胎儿和成人肾脏中的结合位点。通过体外放射自显影观察[125I] - 内皮素-1、-2、-3的结合位点，并通过光密度测定法定量。在成人和胎儿组织中，皮质、髓质和肾血管中均存在特异性结合位点。未标记的内皮素和与内皮素序列高度同源的肽类沙拉毒素，以9.8至0.023 nM范围内的IC50抑制[125I] - 内皮素-1的结合，而不相关的肽类（血管紧张素II、心房利钠肽）和钙拮抗剂尼群地平未能竞争[125I] - 内皮素-1的结合位点。线性Scatchard分析显示，胎儿肾脏中结合位点的数量（以每组织当量：TE表示）始终高于成人肾脏，而皮质、髓质和血管中的亲和力无显著差异（胎儿/成人：皮质KD 43.4±19.6/55.9±16.7 nM；BMax 13.5±7.8/2.7±1.3 fmol/mg TE；髓质KD 26.3±10.9/34.6±7.4 nM；BMax 10.1±0.9/3.7±1.1 fmol/mg TE；血管KD 41.1±22.9/23.7±8.1 nM；BMax 12.9±3.9/4.1±1.2 fmol/mg TE）。髓质毛细血管和静脉在人和大鼠肾脏中显示出强烈结合，这可能对急性肾衰竭的病理生理学很重要。成人和胎儿的肾小球仅有少数结合位点。这与大鼠肾脏中的发现形成对比，大鼠肾脏中的肾小球具有高浓度的内皮素结合位点；尽管这本身并不排除其影响，但确实指出需要更仔细地审视内皮素对人类肾小球具有相关作用这一假设。胎儿肾脏中广泛而强烈的结合可能表明内皮素在肾脏成熟过程中起作用。
