CHARACTERIZATION OF A LOW-MOLECULAR-WEIGHT NA-K-ATPASE INHIBITOR OF URINARY ORIGIN

It has been demonstrated that expansion of extracellular fluid volume induces the release of a low-molecular-weight natriuretic and sodium-p otassium-activated adenosine triphosphatase inhibiting hormone (NKAI). In this study, we used a highly purified hormone extracted from poole d hypertensive urines (u-NKAI). Like ouabain, this compound was found to be a potent inhibitor of the sodium-potassium-activated adenosine-t riphosphatase and potassium-stimulated paranitrophenyl phosphatase enz yme systems as well as a vasoconstrictor in vitro. In contrast to ouab ain, which is a competitive inhibitor of both enzyme systems with resp ect to potassium, u-NKAI is noncompetitive. Furthermore, u-NKAI differ s from ouabain by its lack of cross-reactivity with digoxin antibodies . In addition, whereas ouabain binds to both high-affinity and low-aff inity binding sites on the sodium-potassium-activated adenosine-tripho sphatase enzyme in the absence of potassium, u-NKAI binds only to the low-affinity binding sites. This study demonstrates that the highly pu rified u-NKAI, although ouabain-like in certain respects, is not an '' endogenous ouabain.''