Kaliuretic peptide: the most potent inhibitor of Na(+)-K+ 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 (kaliuretic 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 37.5%, 27.5%, 20%, and 0%, 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 E2 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 E2 revealed that kaliuretic peptide > long-acting natriuretic peptide > vessel dilator increased prostaglandin E2 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.
Chiou
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Department of Medicine, University of South Florida Health Sciences Center, Tampa, USA.
Vesely
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D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002417:Cattle; D002462:Cell Membrane / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000201:enzymology*; D007672:Kidney Cortex / Q000201:enzymology; D007679:Kidney Medulla / Q000201:enzymology; D007700:Kinetics; D010042:Ouabain / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D011498:Protein Precursors / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D014665:Vasodilator Agents / Q000494:pharmacology*
D010446:Peptide Fragments; D011498:Protein Precursors; D014665:Vasodilator Agents; C075322:atrial natriuretic factor precursor (79-98); D000804:Angiotensin II; D010042:Ouabain; D009320:Atrial Natriuretic Factor; D000254:Sodium-Potassium-Exchanging ATPase