Studies on valinomycin inhibition of synaptosome-fraction protein synthesis.
The ionophore valinomycin inhibited adult and neonatal synaptosome fraction protein synthesis with half-maximal inhibition at approximately 10nM. Valinomycin had no effect on [3H]leucine uptake into synaptosomes at high or low external [K+]. Synaptosome-fraction protein synthesis was dependent on [K+]e reaching a maximum at 25mM-K+. Valinomycin inhibition of protein synthesis was not reversed at high [K+]e. Valinomycin failed to influence the intrasynaptosomal [K+] even at zero [K+]e. A significant increase in State-4 respiration of synaptosomal fractions was found at 5nM-valinomycin with a decrease in the respiratory control index. At these concentrations of valinomycin there was no inhibition of the ADP-stimulated (State 3) respiration rate. Valinomycin had no effect on cerebral microsomal protein synthesis in vitro, which was inhibited by puromycin (100 micrograms/ml) or the absence of ATP. Valinomycin, 2,4-dinitrophenol and KCN inhibition of protein synthesis was not reversed by added ATP, suggesting impermeability of the membrane to ATP. Valinomycin induced a rapid fall in synaptosome ATP content not observed with atractylate or ouabain. Valinomycin inhibition of protein synthesis under these conditions is secondary to uncoupling of mitochondrial oxidative phosphorylation with a subsequent decrease in intraterminal ATP necessary for translation.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D003864:Depression, Chemical; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology; D014176:Protein Biosynthesis; D051381:Rats; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D014634:Valinomycin / Q000494:pharmacology*
D000596:Amino Acids; D014634:Valinomycin; D000255:Adenosine Triphosphate; D011188:Potassium