The interaction of canrenone with the Na+,K+ pump in human red blood cells.
Canrenone inhibits 30-40% of ouabain-sensitive Na+ efflux in human red cells. Half-maximal inhibition was obtained with a canrenone concentration = 86 +/- 37 mumol/l (mean +/- SD of 13 experiments). The partial inhibition of the Na+,K+ pump appears to be mediated at the digitalis receptor site with an apparent dissociation constant (Kc) = 200 +/- 130 mumol/l (mean +/- SD). Further evidence suggesting that canrenone is a partial agonist at the digitalis receptor site was obtained by the observation that it decreases the apparent affinity of the Na+,K+ pump for external K+. However, in contrast to ouabain, canrenone decreases the apparent pump affinity for internal Na+. Our results show that, at physiological cell Na+ levels canrenone is able to enhance the inhibition of the Na+,K+ pump by low doses of ouabain. Conversely, in cells treated with high concentrations of cardiac glycosides (in which cell Na+ content increases), canrenone is able to restimulate the blocked pumps.
Garay
R P
RP
Diez
J
J
Nazaret
C
C
Dagher
G
G
Abitbol
J P
JP
D002192:Canrenone / Q000494:pharmacology*; D004357:Drug Synergism; D004910:Erythrocyte Membrane / Q000201:enzymology; D006801:Humans; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000097:blood; D011245:Pregnadienes / Q000494:pharmacology*; D012964:Sodium / Q000097:blood; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000097:blood* / Q000378:metabolism
D011245:Pregnadienes; D010042:Ouabain; D002192:Canrenone; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium