Verity M A, Cheung M K, Brown W J
Biochem J. 1981 Apr 15;196(1):25-32. doi: 10.1042/bj1960025.
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.
离子载体缬氨霉素可抑制成年和新生突触体组分的蛋白质合成，在约10nM时产生半数最大抑制作用。缬氨霉素在高或低细胞外[K⁺]浓度下对[³H]亮氨酸摄入突触体均无影响。突触体组分蛋白质合成依赖于[K⁺]e，在25mM - K⁺时达到最大值。缬氨霉素对蛋白质合成的抑制在高[K⁺]e时不会逆转。即使在细胞外[K⁺]为零时，缬氨霉素也未能影响突触体内的[K⁺]。在5nM缬氨霉素时发现突触体组分的状态4呼吸显著增加，呼吸控制指数降低。在这些缬氨霉素浓度下，对ADP刺激的（状态3）呼吸速率没有抑制作用。缬氨霉素在体外对脑微粒体蛋白质合成无影响，嘌呤霉素（100微克/毫升）或缺乏ATP可抑制其合成。缬氨霉素、2,4 -二硝基苯酚和KCN对蛋白质合成的抑制作用不会因添加ATP而逆转，表明膜对ATP不可渗透。缬氨霉素可导致突触体ATP含量迅速下降，而苍术苷或哇巴因则不会。在这些条件下，缬氨霉素对蛋白质合成的抑制作用继发于线粒体氧化磷酸化的解偶联，随后翻译所需的线粒体内ATP减少。
