Salinomycin effects on mitochondrial ion translocation and respiration.
The effects of salinomycin on alkali cation transport and membrane functions in rat liver mitochondria have been investigated. After potassium uptake, stimulated by valinomycin or monazomycin in the presence of adenosine 5'-triphosphate, salinomycin caused rapid release of K(+) from mitochondria. Salinomycin reversed valinomycin- or monazomycin-induced oscillatory swelling of mitochondria preloaded with K(+), Rb(+), and Na(+) but was without effect on Li(+) or Cs(+) preloaded mitochondria. Salinomycin blocked the retention of K(+) more effectively than the retention of Rb(+) or Na(+). Salinomycin inhibited both coupled and uncoupled respiration with strict substrate specificity in medium of low but not in high K(+) concentration. The oxidation of glutamate, alpha-ketoglutarate, and malate plus pyruvate was inhibited by salinomycin, but that of beta-hydroxybutyrate or succinate was not significantly affected. Salinomycin inhibited adenosine triphosphatase activity of mitochondria induced by valinomycin or monazomycin in K(+) and Rb(+) medium without significantly affecting adenosine triphosphatase activity in Li(+), Na(+), or Cs(+) medium. Oxidative phosphorylation in mitochondria was inhibited by salinomycin but the inhibitory effect of salinomycin lacked the substrate specificity observed for respiration. It is proposed that salinomycin perturbs mitochondrial functions by acting as a mobile carrier for alkali cations through membranes.
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D006027:Glycosides / Q000494:pharmacology; D066298:In Vitro Techniques; D018942:Macrolides; D008670:Metals / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects*; D011188:Potassium / Q000378:metabolism; D011714:Pyrans / Q000494:pharmacology; D051381:Rats; D014634:Valinomycin / Q000494:pharmacology; D000095662:Polyether Polyketides
D000251:Adenosine Triphosphatases; D000900:Anti-Bacterial Agents; D006027:Glycosides; D018942:Macrolides; D008670:Metals; D011188:Potassium; D011714:Pyrans; D014634:Valinomycin; C005240:monazomycin; C010327:salinomycin; D000095662:Polyether Polyketides