Localization and quantification of [125I]-endothelin binding sites in human fetal and adult kidneys--relevance to renal ontogeny and pathophysiology.

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.