Two brain inhibitors inhibit renal Na,K-ATPases without recognizing the species-dependent variation of their ouabain-sensitivity.

The membrane Na,K-ATPase is the driving force for sodium reabsorption in the kidney. Accordingly, Na,K-ATPase has been proposed to be a likely target for the action of a putative natriuretic hormone which would modulate sodium excretion by partial inhibition of renal Na,K-ATPase activity. To examine this hypothesis, it is necessary to isolate inhibitors from body fluids and tissues and to characterize their interaction with Na,K-ATPase in comparison to the plant inhibitors ouabain. Two inhibitors extracted from hypothalamus or hypothalamus-hypophysis have been compared to ouabain with regard to the shape of the dose-response curves and species-dependence. Ouabain inhibited renal Na,K-ATPase with dose-response curves spanning 3 to 5 orders of magnitude and marked species-dependence. By contrast, the brain inhibitors blocked the ATPase activity of isolated renal Na,K-ATPase with steep dose-response curves without species-dependence. Thus, the brain inhibitors are clearly distinct from plant ouabain; their chemical structures remain to be established.