DRUGS AFFECTING SODIUM TRANSPORT IN HUMAN ERYTHROCYTE GHOSTS

¹ Department of Pharmacology, Cornell University Medical College, New York, New York

Effects of various drugs on Na⁺ efflux in resealed ghosts were studied. Inhibitors of Na⁺, K⁺-activated adenosine triphosphatase (Na⁺, K⁺-ATPase)(ouabain, ethacrynic acid, oligomycin, chlorpromazine and furosemide) blocked the coupled Na⁺, K⁺-pump when this was driven by ATP placed inside the ghosts. Furosemide, unlike the other inhibitors, did not affect the pump when it was energized by the metabolism of substrates to lactate. This suggests that the mechanism of inhibition of Na⁺, K⁺-ATPase by furosemide is different from those of other tested inhibitors. In agreement with the known effects of oligomycin on Na⁺, K⁺-ATPase, it was found that this drug does not produce complete inhibition of the pump. All of the above drugs also caused partial inhibition of Na⁺ efflux into a Na⁺, K⁺-free medium. It is concluded that a portion of nonenergized Na⁺ efflux is due to the spontaneous movement of Na⁺ on the carrier of the pump. Dipyridamole inhibited the substrate-driven pump. This seems to be an indirect effect of the drug due to inhibition of the purine nucleoside transport system. Local anesthetics inhibited only that component of Na⁺ efflux which is not carrier mediated. This component was also affected by furosemide and chhorpromazine, suggesting that the actions of these drugs on cell membrane are not as specific as those of the other tested inhibitors of Na⁺, K⁺-ATPase.