An investigation of the effects of aminoglycoside antibiotics on Na+-K+ ATPase as a possible mechanism of toxicity.

An investigation was made of the effect of aminoglycoside antibiotics on Na+-K+ ATPase to determine whether their toxicity might be attributable to an inhibition of this enzyme. Three preparations were used: human erythrocyte ghosts; microsomal fractions of the cortex and outer medulla of the guinea-pig kidney; rat isolated renal tubules. In all three preparations marked inhibition of Na+-K+ ATPase (50-100%) was seen only at very high concentrations of drug (10(-2)M). Although aminoglycoside antibiotics are known to accumulate to high concentrations in vivo, particularly in the renal cortex, it is argued that these findings suggest that an effect on Na+-K+ ATPase is unlikely to be their primary mechanism of toxicity.