title: Canrenone as a partial agonist at the digitalis receptor site of sodium-potassium-activated adenosine triphosphatase.
abstract: Canrenone, a spironolactone metabolite, was tested for its possible effects on (Na+-K+) adenosine triphosphatase (ATPase) activity [Mg++-dependent, (Na+-K+)-activated ATP phosphohydrolase (E.C.3.6.1.3) and ouabain interaction with the enzyme. Canrenone competitively antagonized the binding of [3H]ouabain to (Na+-K+)ATPase and inhibited (Na+-K+)ATPase activity. The multiple inhibition technique was used to demonstrate that canrenone is a partial inhibitor of (Na+-K+)ATPase, mutually exclusive with respect to ouabain. Comparative studies of the effects of ouabain and canrenone on potassium-dependent p-nitrophenylphosphatase activity (E.C.9.6.1.7) and potassium activation of (Na+-K+)ATPase confirmed that ouabain and canrenone interacted with the same receptor site. The finding that canrenone is a partial agonist may explain the results of previous in vivo studies showing that spironolactone and the allied drug to potassium conrenoate have either a positive inotropic action or an antagonistic effect against digitalis toxicity.
mesh_terms: D009597:4-Nitrophenylphosphatase / Q000378:metabolism; D000818:Animals; D002191:Canrenoic Acid / Q000494:pharmacology; D002192:Canrenone / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D010042:Ouabain / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D011245:Pregnadienes / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D011955:Receptors, Drug / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013148:Spironolactone / Q000494:pharmacology
chemical_list: D011245:Pregnadienes; D011955:Receptors, Drug; C027082:digitalis receptor; D013148:Spironolactone; D010042:Ouabain; D002192:Canrenone; D002191:Canrenoic Acid; D009597:4-Nitrophenylphosphatase; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium