Autocrine role for the endothelin-B receptor in the secretion of adrenomedullin.
Autocrine role for the endothelin-B receptor in the secretion of adrenomedullin.
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DOI：
10.1161/01.hyp.32.5.917
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发表时间：
1998-11
期刊：
影响因子：
8.3
通讯作者：
M. Jougasaki;J. Schirger;R. Simari;J. Burnett
中科院分区：
文献类型：
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作者：
M. Jougasaki;J. Schirger;R. Simari;J. Burnett
肾上腺髓质素最初在人类嗜铬细胞瘤中发现，是一种血管内皮细胞和平滑肌细胞来源的血管舒张肽和利尿钠肽。尽管内皮素-1 (ET-1) 被认为是一种内皮来源的血管收缩和生长促进肽，但更重要的是，它可能作为一种自分泌因子发挥作用，并通过与内皮素-B (ETB) 受体亚型相关的机制释放血管舒张物质，例如一氧化氮。本研究旨在确定 ETB 受体刺激培养的犬主动脉内皮细胞分泌肾上腺髓质素。我们首先尝试使用免疫组织化学和 Northern 印迹分析来确定犬主动脉内皮细胞中肾上腺髓质素的存在和产生，结果表明犬主动脉内皮细胞中存在肾上腺髓质素免疫反应性和肾上腺髓质素 mRNA。其次，犬主动脉内皮细胞分泌肾上腺髓质素具有时间依赖性，分泌率为每24小时15.7+/-1.5 pg/10(5)个细胞。此外，免疫组织化学显示犬主动脉内皮细胞中存在 ETB 受体，并且 sarafotoxin S6c 刺激 ETB 受体会增加犬主动脉内皮细胞的肾上腺髓质素产生和分泌。这种作用可以被 ETB 受体拮抗剂 IRL-2500 阻断，但不能被 ETA 受体拮抗剂 FR-139317 阻断。这些研究首次报道了 ETB 受体在血管舒张和利尿钠肽肾上腺髓质素释放中的额外自分泌作用，并提出了另一种受 ET 受体亚型调节的重要血管活性系统。
Adrenomedullin, originally discovered in human pheochromocytoma, is a vasodilating and natriuretic peptide of vascular endothelial and smooth muscle cell origin. Although endothelin-1 (ET-1) has been implicated as a vasoconstricting and growth-promoting peptide of endothelial origin, it may more importantly function as an autocrine factor and release vasodilatory substances such as nitric oxide by mechanisms linked to the endothelin-B (ETB) receptor subtype. The present study was designed to establish that the ETB receptor stimulates the secretion of adrenomedullin from cultured canine aortic endothelial cells. We first sought to determine the presence and production of adrenomedullin in canine aortic endothelial cells using immunohistochemistry and Northern blot analysis, which revealed that adrenomedullin immunoreactivity and adrenomedullin mRNA were present in canine aortic endothelial cells. Second, adrenomedullin was time-dependently secreted from canine aortic endothelial cells, with a secretion rate of 15.7+/-1.5 pg/10(5) cells per 24 hours. Furthermore, immunohistochemistry revealed the presence of the ETB receptor in canine aortic endothelial cells, and ETB receptor stimulation by sarafotoxin S6c increased adrenomedullin production and secretion from canine aortic endothelial cells. Such actions were blocked with the ETB receptor antagonist IRL-2500 but not with ETA receptor antagonist FR-139317. These studies are the first to report an additional autocrine role of the ETB receptor in the release of vasodilating and natriuretic peptide adrenomedullin, and they suggest another important vasoactive system regulated by the ET receptor subtype.