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

To elucidate the posttranslational processing of gamma-human atrial natriuretic polypeptide (human atrial natriuretic factor-[1-126]), which is a prohormone of alpha-human atrial natriuretic polypeptide (human atrial natriuretic factor-[99-126]), and the secretion of gamma-human atrial natriuretic polypeptide-derived peptides from the heart, we established a radioimmunoassay specific for the N-terminal sequence of gamma-human atrial natriuretic polypeptide, gamma-human atrial natriuretic polypeptide-(1-25), as well as a radioimmunoassay for alpha-human atrial natriuretic polypeptide. With the aid of the radioimmunoassays for gamma-human atrial natriuretic polypeptide-(1-25) and for alpha-human atrial natriuretic polypeptide, we detected 290 +/- 35.6 pg/ml of gamma-human atrial natriuretic polypeptide-(1-25)-like immunoreactivity in plasma from healthy humans, while the simultaneously determined plasma alpha-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 gamma-human atrial natriuretic polypeptide-(1-25)-like immunoreactivity was composed of a component (molecular weight, 10,000) without alpha-human atrial natriuretic polypeptide-like immunoreactivity, while the plasma alpha-human atrial natriuretic polypeptide-like immunoreactivity was composed of alpha-human atrial natriuretic polypeptide with a molecular weight of 3000. In patients with heart diseases, the plasma gamma-human atrial natriuretic polypeptide-(1-25)-like immunoreactivity level showed a concomitant and graded increase, with the plasma alpha-human atrial natriuretic polypeptide-like immunoreactivity 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.(ABSTRACT TRUNCATED AT 250 WORDS)