Eguchi S, Hirata Y, Imai T, Marumo F
Second Department of Internal Medicine, Tokyo Medical and Dental University, Japan.
J Cardiovasc Pharmacol. 1995;26 Suppl 3:S279-83.
To elucidate the role of endothelin-1 (ET-1) as an autocrine growth factor for vascular endothelial cells (ECs), we studied the effects of phosphoramidon, an inhibitor of ET-1-converting enzyme, on the production of ET-1-like immunoreactivity (LI), [125I]ET-1 binding activity, ETB receptor mRNA expression, phosphoinositide breakdown, and DNA synthesis in cultured bovine carotid artery ECs. Phosphoramidon dose-dependently decreased ET-1-LI production but reciprocally increased [125I]ET-1 binding capacity. ET-1 and ET-3 equipotently inhibited the binding of [125I]ET-1 only in the presence of phosphoramidon. Northern blot analysis revealed that ETB receptor mRNA expression was more evident in phosphoramidon-treated cells than in nontreated cells. In the presence of phosphoramidon, ET-1 and ET-3 equipotently stimulated inositol 1,4,5-trisphosphate formation and [3H]-thymidine incorporation into cultured ECs. Both phosphoramidon and anti-ET-1 antibody inhibited basal [3H]thymidine incorporation. These data suggest that endogenous ET-1 constitutively secreted by ECs is an autocrine growth factor via ETB receptors.
为阐明内皮素-1（ET-1）作为血管内皮细胞（ECs）自分泌生长因子的作用，我们研究了ET-1转换酶抑制剂磷酰胺素对培养的牛颈动脉ECs中ET-1样免疫反应性（LI）产生、[125I]ET-1结合活性、ETB受体mRNA表达、磷酸肌醇分解及DNA合成的影响。磷酰胺素剂量依赖性地降低ET-1-LI产生，但相应增加[125I]ET-1结合能力。仅在存在磷酰胺素的情况下，ET-1和ET-3对[125I]ET-1的结合具有同等抑制作用。Northern印迹分析显示，磷酰胺素处理的细胞中ETB受体mRNA表达比未处理细胞更明显。在存在磷酰胺素的情况下，ET-1和ET-3对培养的ECs中肌醇1,4,5-三磷酸形成及[3H]胸腺嘧啶掺入具有同等刺激作用。磷酰胺素和抗ET-1抗体均抑制基础[3H]胸腺嘧啶掺入。这些数据表明，ECs组成性分泌的内源性ET-1是通过ETB受体的自分泌生长因子。
