Cardiolipins are 'in vitro' inhibitors of rat brain (Na+ + K+)-dependent ATPases. A probable mechanism of action.
Cardiolipins were found to potentiate the 'in vitro' inhibitory activity of (-)-delta 9-tetrahydrocannabinol on (Na+ + K+)-dependent rat brain ATPases. The compounds were found to be powerful inhibitors by themselves. At optimal concentrations of cations (Na+, K+, Mg2+), the compounds were found to be noncompetitive inhibitors of ATP (Ki = 3.5 x 10(-6) M) and 'uncompetitive' inhibitors of Na+. From gas-liquid chromatographic analysis of the cardiolipin preparations it can be inferred that their effectiveness as inhibitors is related to the linoleic acid contents. The preliminary data presented here suggest that cardiolipins inhibit the Na+-dependent phosphorylation step in the hydrolysis of ATP. Based on the observations reported in this work, a hypothesis is presented suggesting that there may be a functional or evolutionary explanation for the paucity of cardiolipins in cell plasma membranes.
D000818:Animals; D001921:Brain / Q000201:enzymology*; D002308:Cardiolipins / Q000494:pharmacology*; D013759:Dronabinol / Q000031:analogs & derivatives / Q000494:pharmacology; D004357:Drug Synergism; D007700:Kinetics; D008861:Microsomes / Q000201:enzymology; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D002308:Cardiolipins; D010042:Ouabain; D013759:Dronabinol; D000254:Sodium-Potassium-Exchanging ATPase; C025351:delta(9)-tetrahydrocannabinolic acid