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.
D000617:Aminoglycosides / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000633:toxicity; D004910:Erythrocyte Membrane / Q000201:enzymology; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000201:enzymology; D007679:Kidney Medulla / Q000201:enzymology; D007684:Kidney Tubules / Q000201:enzymology; D008297:Male; D008861:Microsomes / Q000201:enzymology; D010710:Phosphates / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D010710:Phosphates; D000254:Sodium-Potassium-Exchanging ATPase