KALIURETIC PEPTIDE - THE MOST POTENT INHIBITOR OF NA plus -K plus -ATPASE OF THE ATRIAL NATRIURETIC PEPTIDES

The present investigation was designed to determine whether atrial natriuretic peptides consisting of amino acids 1-30 (i.e. long-acting natriuretic peptide), 31-67 (vessel dilator), 79-98 (kaliuretie peptide), and 99-126 [atrial natriuretic factor (ANF)] of the 126 amino acid ANF prohormone inhibit sodium-potassium-ATPase as part of their mechanism(s) of action for producing a natriuresis and/or kaliuresis. Kaliuretic peptide, long-acting natriuretic peptide, vessel dilator and ANF at their 10(-11) M concentrations inhibited Na+-K+-ATPase 39.5%, 27.8%, 19.2%, and 4% respectively, in bovine renal medulla, whereas their inhibition in renal cortical membranes was 31.5%, 27.5%, 20%, and O%, respectively. Ouabain (0.5 mM) inhibited kidney medullary Na+-K+-ATPase 45% and in the cortex, 38%. There was no additive effect of any of these peptides with ouabain suggesting that they are interacting with the same site on the Na+-K+-ATPase as ouabain. To help elucidate the mechanism of these peptides' interaction with Na+-K+-ATPase, naproxen (0.5 mM), an inhibitor of prostaglandin synthesis, and direct measurement of prostaglandin E(2) by RIA were used. Naproxen completely blocked the inhibition of Na+-K+-ATPase by kaliuretic peptide, long-acting natriuretic peptide, and vessel dilator suggesting that their inhibition of Na+-K+-ATPase in both the kidney medulla and cortex are mediated by prostaglandins. Direct measurement of prostaglandin E(2) revealed that kaliuretic peptide > long-acting natriuretic peptide > vessel dilator increased prostaglandin E(2) synthesis, whereas ANF did not have any effect. Of interest, angiotensin II and ouabain inhibition of Na+K+-ATPase were also completely blocked by naproxen.