Further biochemical characterization of an Na+ pump inhibitor purified from human urine

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Abstract
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 antidigoxin 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 (a) it reversibly inhibited Na+,K+-ATPase activity; (b) it inhibited Na+,K+-ATPase non-competitively with ATP; (c) its inhibitory effect was facilitated by Na+; (d) K+ decreased its inhibitory effect on Na+,K+-ATPase; (e) it competitively inhibited ouabain binding to the enzyme; (f) its binding was maximal in the presence of Mg2+ and Pi; (g) it decreased the Na+ pump activity in human erythrocytes; (h) it reduced serotonin uptake by human platelets; and (j) it was diuretic and natriuretic in rat bioassay. The endalin differed from ouabain in only three aspects: (a) its inhibitory effect was not really specific for Na+,K+-ATPase; (b) its binding to the enzyme was undetectable in the presence of Mg2+ and ATP; (c) 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.