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-potassium-activated adenosine triphosphatase inhibiting hormone (NKAI). In this study, we used a highly purified hormone extracted from pooled hypertensive urines (u-NKAI). Like ouabain, this compound was found to be a potent inhibitor of the sodium-potassium-activated adenosine-triphosphatase and potassium-stimulated paranitrophenyl phosphatase enzyme systems as well as a vasoconstrictor in vitro. In contrast to ouabain, which is a competitive inhibitor of both enzyme systems with respect to potassium, u-NKAI is noncompetitive. Furthermore, u-NKAI differs from ouabain by its lack of cross-reactivity with digoxin antibodies. In addition, whereas ouabain binds to both high-affinity and low-affinity binding sites on the sodium-potassium-activated adenosine-triphosphatase enzyme in the absence of potassium, u-NKAI binds only to the low-affinity binding sites. This study demonstrates that the highly purified u-NKAI, although ouabain-like in certain respects, is not an "endogenous ouabain."
Weiler
E W
EW
Trace Element Laboratory, Division of Nephrology/Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048.
Gonick
H C
HC
Prins
B A
BA
Purdy
R E
RE
Weber
M A
MA
D009597:4-Nitrophenylphosphatase / Q000037:antagonists & inhibitors; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000302:isolation & purification* / Q000652:urine; D006801:Humans; D007700:Kinetics; D008297:Male; D008970:Molecular Weight; D045283:Natriuretic Agents / Q000302:isolation & purification* / Q000494:pharmacology / Q000652:urine; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D045283:Natriuretic Agents; D010042:Ouabain; D009597:4-Nitrophenylphosphatase; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium