Renal synthesis of atriopeptin-like protein in physiology and pathophysiology

Abstract

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.

Urodilatin (Ularitide, INN): A Renal Natriuretic Peptide

“…The rate o f degradation o f URO is signif icantly lower than that o f CDD/ANP-99-126. a result which was confirmed by other groups [64.66] 58] These investigations may explain the differences o f tile in vivo kinetics between the two main A-type NPs. These differences, however, concern results described for long-term infusion [67J, but not those described for bolus injections [68].…”

Increased C-type natriuretic peptide mRNA expression in the kidney of diabetic rats

“…Our previous reports demonstrated that renal ANP mRNA is significantly enhanced and the elevation of urinary ANP excretion correlated well with urinary sodium excretion in diabetic rats (Shin et al 1997) and deoxycorticosterone acetate (DOCA)-treated rats (Lee et al 1996). These findings support the proposal that renal-synthesized natriuretic peptide may be related to the change in water-electrolyte balance (Greenwald et al 1991). In animals and humans with diabetes, alterations in extracellular and exchangeable sodium have been found (Ortola et al 1987, Allen et al 1990) and have been thought to lead to changes in plasma ANP A B C Figure 4 Representative autoradiographs (upper panels) of the amplification of CNP and -actin mRNA by RT-PCR followed by Southern blot analysis in the renal cortex (A), outer medulla (B) and inner medulla (C) from normal control (NC, n=8), diabetic (DM, n=8), insulin-treated diabetic (ITDM, n=7) and low salt diet-treated diabetic (LSD-DM, n=7) rats on the 60th day after administration of citric buffer or streptozotocin.…”

Gentamicin Decreases Guanylyl Cyclase Activity in Rat Glomerulus

“…Among others, natriuretic peptides (NPs) and nitric oxide (NO) have been widely implicated in the regulation of urinary sodium excretion and glomerular filtration rate (GFR) [4,5] . Both NPs and NO induce the generation of 3 ,5 -cyclic monophosphate (cGMP), in which the former activates the membrane-bound particulate guanylyl cyclase (GC) [6] and the latter activates thecytoplasmic soluble GC [7] .…”