Further biochemical characterization of an Na+ pump inhibitor purified from human urine.
An increase in endogenous Na+,K+-ATPase inhibitor(s) with digitalis-like properties has been reported in chronic renal insufficiency, in Na+-dependent experimental hypertension and in some essential hypertensive patients. The present study specifies some properties and some biochemical characteristics of a semipurified compound from human urine having digitalis-like properties. The urine-derived inhibitor (endalin) inhibits Na+,K+-ATPase activity and [3H]-ouabain binding, and cross-reacts with anti-digoxin antibodies. The inhibitory effect on ATPases of endalin is higher on Na+,K+-ATPase than on Mg2+-ATPase and Ca2+-ATPase. The mechanism of endalin action on highly purified Na+,K+-ATPase was compared to that of ouabain and was similar in that it reversibly inhibited Na+,K+-ATPase activity; it inhibited Na+,K+-ATPase non-competitively with ATP; its inhibitory effect was facilitated by Na+; K+ decreased its inhibitory effect on Na+,K+-ATPase; it competitively inhibited ouabain binding to the enzyme; its binding was maximal in the presence of Mg2+ and Pi; it decreased the Na+ pump activity in human erythrocytes; it reduced serotonin uptake by human platelets; and it was diuretic and natriuretic in rat bioassay. The endalin differed from ouabain in only three aspects: its inhibitory effect was not really specific for Na+,K+-ATPase; its binding to the enzyme was undetectable in the presence of Mg2+ and ATP; it was not kaliuretic in rat bioassay. Endalin is a reversible and partial specific inhibitor of Na+,K+-ATPase, its Na+,K+-ATPase inhibition closely resembles that of ouabain and it could be considered as one of the natriuretic hormones.
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D000818:Animals; D001665:Binding Sites; D001792:Blood Platelets / Q000378:metabolism; D001921:Brain / Q000201:enzymology; D002298:Cardenolides; D002384:Catalysis; D004077:Digoxin; D004285:Dogs; D006801:Humans; D007668:Kidney / Q000201:enzymology; D010042:Ouabain / Q000032:analysis / Q000494:pharmacology; D011817:Rabbits; D012503:Saponins; D012701:Serotonin / Q000097:blood; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000502:physiology / Q000652:urine
D002298:Cardenolides; D012503:Saponins; C034504:digoxin-like factors; D012701:Serotonin; D010042:Ouabain; D004077:Digoxin; D000251:Adenosine Triphosphatases; D000254:Sodium-Potassium-Exchanging ATPase