Bagnato A, Venuti A, Di Castro V, Marcante M L
Laboratory of Molecular Pathology and Ultrastructure, Regina Elena Cancer Institute, Rome, Italy.
Biochem Biophys Res Commun. 1995 Apr 6;209(1):80-6. doi: 10.1006/bbrc.1995.1473.
Endothelin-1 has a wide range of pharmacological effects in various tissues and acts as autocrine/paracrine factor. The potential of ET-1 to function as an autocrine growth factor was evaluated in normal human keratinocytes. Radioligand binding studies showed that 125I-ET-1 bound to a single class of high-affinity-binding sites on the surface of the cells. The dissociation constant was 0.045 nM with receptor numbers of 1700 sites/cell. Treatment with serum caused increases in expression of binding sites (3500 sites/cell), with no change in binding affinity. ET-1 stimulated thymidine incorporation in these cells that expressed ET receptors. An ET antagonist selective for the ETA receptor subtype (BQ 123) inhibited DNA synthesis stimulated by ET-1 and reduced the basal growth rate of unstimulated cells. These data suggest that the ET-1 induced DNA synthesis is mediated by ETA receptor subtype and that endogenously produced ET-1 promotes the autocrine proliferation of keratinocytes.
内皮素 -1 在多种组织中具有广泛的药理作用，并作为自分泌/旁分泌因子发挥作用。在正常人角质形成细胞中评估了内皮素 -1 作为自分泌生长因子的潜力。放射性配体结合研究表明，125I-内皮素 -1 与细胞表面一类单一的高亲和力结合位点结合。解离常数为 0.045 nM，受体数量为 1700 个位点/细胞。血清处理导致结合位点表达增加（3500 个位点/细胞），而结合亲和力没有变化。内皮素 -1 刺激表达内皮素受体的这些细胞中的胸苷掺入。对 ETA 受体亚型具有选择性的内皮素拮抗剂（BQ 123）抑制了内皮素 -1 刺激的 DNA 合成，并降低了未刺激细胞的基础生长速率。这些数据表明，内皮素 -1 诱导的 DNA 合成是由 ETA 受体亚型介导的，并且内源性产生的内皮素 -1 促进角质形成细胞的自分泌增殖。
