Secretion of N-terminal fragment of γ-human atrial natriuretic polypeptide

To elucidate the posttranslational processing of γ-human atrial natriuretic polypeptide (human atrial natriuretic factor-[1-126]), which is a prohormone of α-human atrial natriuretic polypeptide (human atrial natriuretic factor-[99-126]), and the secretion of γ-human atrial natriuretic polypeptide-derived peptides from the heart, we established a radioimmunoassay specific for the N-terminal sequence of γ-human atrial natriuretic polypeptide, γ-human atrial natriuretic polypeptide-(1-25), as well as a radioimmunoassay for α-human atrial natriuretic polypeptide. With the aid of the radioimmunoassays for γ-human atrial natriuretic polypeptide-(1-25) and for γ-human atrial natriuretic polypeptide, we detected 290 ± 35.6 pg/ml of γ-human atrial natriuretic polypeptide-(1-25 Hike immunoreactivity in plasma from healthy humans, while the simultaneously determined plasma α-human atrial natriuretic polypeptide-like immunoreactivity level was 20.9 ± 2.8 pg/ml. Correlation between the two values was significant. High performance gel permeation chromatographic analysis revealed that the plasma γ-human atrial natriuretic polypeptide-(1-25)-like Immunoreactivity was composed of a component (molecular weight, 10,000) without α-human atrial natriuretic polypeptide-like immunoreactivity, while the plasma γ-human atrial natriuretic polypeptide-like immunoreactivity was composed of α-human atrial natriuretic polypeptide with a molecular weight of 3000. In patients with heart diseases, the plasma γ-human atrial natriuretic polypeptide-(1-25)-like immunoreactivity level showed a concomitant and graded increase, with the plasma α-human atrial natriuretic polypeptide-like unmunoreactivity level in agreement with the severity of the disease. There were significant positive correlations between the two immunoreactivity levels and right or left atrial pressure. These results suggest cosecretion of 10 K N-terminal fragment of γ-human atrial natriuretic polypeptide and α-human atrial natriuretic polypeptide into the circulation in response to increased atrial stretch.