Renal synthesis of atriopeptin-like protein in physiology and pathophysiology

J. E. Greenwald, P. Needleman, M. R. Wilkins and G. F. Schreiner Department of Medicine, Pharmacology, and Pathology, Washington University School of Medicine, St. Louis 63108. Atriopeptin is synthesized in mammalian atria as a 126-amino acid (14 kDa) prohormone, but it is secreted and circulates as a 28-amino acid (2.5 kDa) peptide. We have demonstrated the synthesis and secretion of an atriopeptin-like peptide in neonatal and adult rat kidney cell cultures. In this study, we evaluated the site of renal synthesis of this protein and its expression in normal rats and rats made nephrotic with puromycin aminonucleoside. The major form of atriopeptin in normal kidneys comigrated with an apparent molecular mass of 2.5 kDa assessed by gel filtration chromatography. However, the major form of this atriopeptin-like protein in nephrotic kidneys was determined to have an apparent molecular mass similar to the heart prohormone. No atriopeptin prohormone was detected in the plasma of nephrotic rats. Localization of this renal atriopeptin-like protein was accomplished by immunocytochemistry of rat kidney frozen sections. Using an antibody generated against either the COOH-terminal or NH3-terminal region of the cardiac atriopeptin prohormone, we detected specific immunostaining in the distal cortical nephron of the nephrotic kidney. This is the first report of the anatomic localization of a renal atriopeptin-like protein and its upregulation in nephrosis.