STRUCTURAL IDENTIFICATION OF BETA-HUMAN AND GAMMA-HUMAN ATRIAL NATRIURETIC POLYPEPTIDES
STRUCTURAL IDENTIFICATION OF BETA-HUMAN AND GAMMA-HUMAN ATRIAL NATRIURETIC POLYPEPTIDES
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DOI：
10.1038/313397a0
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发表时间：
1985-01-01
期刊：
影响因子：
64.8
通讯作者：
MATSUO, H
中科院分区：
文献类型：
--
作者：
KANGAWA, K;FUKUDA, A;MATSUO, H
最近在人和大鼠心房组织中发现了不同链长的心房利钠肽（ANP）。其有效的利钠利尿活性表明其在调节细胞外液容量和电解质平衡中的关键作用。此外，还克隆并鉴定了编码其前体的人9和大鼠10 - 12的cDNA。人心房提取物中的利尿钠活性包括三种不同的组分（α，相对分子质量（Mr）≤ 3，000; β，Mr ≤ 6，000; γ，Mr ≤ 13，000）1。然而，到目前为止，只有3,000-Mr肽，α-人心房多肽（α-hANP），包含28个氨基酸，已被确定1。本文报道了两种新的高Mr hANP的纯化和序列分析，即β-hANP和γ-hANP，这两种hANP都具有利钠和利尿活性。γ-hANP由126个氨基酸组成，在其羧基末端携带α-hANP序列。对γ-hANP的鉴定表明，该肽是hANP的最大形式，是由151个残基的信号肽去除26个残基后直接加工而成的。相比之下，β-hANP（56个残基）包含α-hANP的反平行二聚体;这种具有生物活性的二聚体肽从未在组织中作为内源性实体发现。
Atrial natriuretic polypeptides (ANPs) of varying chain length have been identified recently in human1and rat2–8atrial tissue. Their potent natriuretic–diuretic activities indicate their key role in the regulation of extracellular fluid volume and electrolyte balance. Furthermore, human9and rat10–12cDNAs encoding their precursor have been cloned and identified. Natriuretic–diuretic activity in human atrial extract comprises three distinct components (α, relative molecular mass (Mr) ∼ 3,000; β,Mr∼ 6,000; γ,Mr∼ 13,000)1. However, only the 3,000-Mrpeptide, α-human atrial poly peptide (α-hANP), comprising 28 amino acids, has so far been identified1. We report here the purification and sequence analysis of two novel hANPs of higherMr, β- and γ-hANP, both of which exhibit natriuretic and hypotensive activity. γ-hANP, composed of 126 amino acids, carries the α-hANP sequence at its carboxy terminus. The identification of γ-hANP reveals that the peptide, being the largest form of hANP, is processed directly from a 151-residue precursor9by removal of a 26-residue signal peptide. In contrast, β-hANP (56 residues) comprises an anti-parallel dimer of α-hANP; such a dimeric peptide possessing bioactivity has never been found in the tissue as an endogenous entity.