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

Abstract

Atrial natriuretic polypeptides (ANPs) of varying chain length have been identified recently in human¹ and rat^2–8 atrial tissue. Their potent natriuretic–diuretic activities indicate their key role in the regulation of extracellular fluid volume and electrolyte balance. Furthermore, human⁹ and rat^10–12 cDNAs encoding their precursor have been cloned and identified. Natriuretic–diuretic activity in human atrial extract comprises three distinct components (α, relative molecular mass (M_r) ∼ 3,000; β, M_r ∼ 6,000; γ, M_r ∼ 13,000) ¹. However, only the 3,000-M_r 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 M_r, 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.