Effects of various inhibitors of oxidative phosphorylation on energy metabolism, macromolecular synthesis and cyclic AMP production in isolated rat thymocytes. A regulating role for the cellular energy state in macromolecular synthesis and cyclic AMP production.
Inhibitors of oxidative phosphorylation such as several triorganotin compounds, oligomycin, 2,4-dinitrophenol and carbonylcyanide p-trifluoromethoxyphenylhydrazone suppress energy metabolism of isolated rat thymocytes as indicated by a reduction of ATP levels, an increase in glucose consumption and by a marked accumulation of lactate. Also these compounds effectively inhibit the incorporation of DNA, RNA and protein precursors into acid-precipitable material of thymocytes. Moreover, the prostaglandin E1-induced elevation of cAMP is markedly reduced by these inhibitors. A correlation is observed between the effects on energy metabolism, macromolecular synthesis and cAMP production, since from a series of trialkyltin chlorides, tri-n-propyltin, tri-n-butyltin and tri-n-hexyltin are very effective inhibitors of these functions, while trimethyltin and tri-n-octyltin affect neither of them; other inhibitors of oxidative phosphorylation, each of them with quite different mechanisms of action, also inhibit macromolecular synthesis and cAMP production. The finding that a rise in intracellular ATP concentrations leads to a reversion of the tri-n-butyltin-induced inhibition of cAMP production and uridine incorporation, indicates a regulating role for the cellular energy state in these aspects of cellular function.
D019297:2,4-Dinitrophenol; D000818:Animals; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology*; D000242:Cyclic AMP / Q000096:biosynthesis*; D004247:DNA / Q000096:biosynthesis; D004140:Dinitrophenols / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009570:Nitriles / Q000494:pharmacology*; D009840:Oligomycins / Q000494:pharmacology*; D014176:Protein Biosynthesis; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014220:Trialkyltin Compounds / Q000494:pharmacology
D004140:Dinitrophenols; D009570:Nitriles; D009840:Oligomycins; D014220:Trialkyltin Compounds; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D012313:RNA; D004247:DNA; D000242:Cyclic AMP; D019297:2,4-Dinitrophenol