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.
Department of Pharmacology, The University of Geneva Medical Center, Switzerland.
B M
BM
Anner
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000201:enzymology; D007031:Hypothalamus / Q000737:chemistry*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D010042:Ouabain / Q000302:isolation & purification / Q000494:pharmacology*; D010902:Pituitary Gland / Q000737:chemistry*; D011817:Rabbits; D051381:Rats; D012756:Sheep; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013045:Species Specificity
D004791:Enzyme Inhibitors; C083016:sodium-potassium ATPase inhibitory factor; D010042:Ouabain; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase