Structural identification of β- and γ-human atrial natriuretic polypeptides

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Abstract
Atrial natriuretic polypeptides (ANPs) of varying chain length have been identified recently in human1 and rat2–8 atrial tissue. Their potent natriuretic–diuretic activities indicate their key role in the regulation of extracellular fluid volume and electrolyte balance. Furthermore, human9 and rat10–12 cDNAs 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-Mr peptide, 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 higher Mr, 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 precursor9 by 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.