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大鼠利钠及血管活性心房肽的纯化、测序与合成

Purification, sequencing and synthesis of natriuretic and vasoactive rat atrial peptide.

作者信息

Atlas S A, Kleinert H D, Camargo M J, Januszewicz A, Sealey J E, Laragh J H, Schilling J W, Lewicki J A, Johnson L K, Maack T

出版信息

Nature. 1984;309(5970):717-9. doi: 10.1038/309717a0.

Abstract

Mammalian atria contain potent natriuretic and diuretic substances which exist in high- and low-molecular-weight forms and which appear to be associated with atrium-specific granules. The natriuretic effect of atrial extract is largely accountable for by its renal haemodynamic effects; atrial extracts also antagonize hormone- and non-hormone-induced contraction of the isolated rabbit aorta and isolated rat kidney vasculature. We have completely purified a low-molecular-weight natriuretic and vasoactive substance from rat atria and characterized it as a 24-amino acid peptide. Synthetic peptide, produced by solid-phase synthesis, mimics biological effects of crude atrial extract and purified peptide; its activity is enhanced by slow oxidation, suggesting a disulphide (Cys 4-Cys 20) configuration for the native peptide. If secreted into blood, this atrial natriuretic peptide (' auriculin B') could be a novel peptide hormone of considerable importance to renal and cardiovascular homeostasis.

摘要

哺乳动物的心房含有有效的利钠和利尿物质,这些物质以高分子量和低分子量形式存在,并且似乎与心房特异性颗粒有关。心房提取物的利钠作用很大程度上归因于其对肾脏血流动力学的影响;心房提取物还能拮抗激素和非激素诱导的离体兔主动脉和离体大鼠肾血管收缩。我们已从大鼠心房中完全纯化出一种低分子量的利钠和血管活性物质,并将其鉴定为一种24个氨基酸的肽。通过固相合成产生的合成肽模拟了粗制心房提取物和纯化肽的生物学效应;其活性通过缓慢氧化而增强,这表明天然肽具有二硫键(Cys 4-Cys 20)结构。如果分泌到血液中,这种心房利钠肽(“耳心素B”)可能是一种对肾脏和心血管稳态具有重要意义的新型肽激素。

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