Dissipation of electrochemical ion gradients induced by carbonyl cyanide p-trifluoromethoxyphenylhydrazone and valinomycin in rabbit reticulocytes as loads of energy metabolism.
The protonophor FCCP and the K+-ionophor valinomycin stimulated the respiration of highly enriched intact rabbit reticulocytes to stationary rates of 200 and 130% of the control at optimal concentrations of about 5 and 50 nmoles/ml cells, respectively. Further increased inhibitor concentrations result in the stepwise decline of respiration rates down to control values. Parallel determinations of adenine nucleotides revealed increasingly lowered ATP/ADP ratios from about 10 to about 5 with valinomycin and 3 with FCCP. The impaired mitochondrial ATP formation was presumably not fully stoichiometrically compensated by elevated glycolytic ATP production as estimated from the rates of lactate production. It can be concluded that both ionophors act mainly at the level of the mitochondrial membrane, although minor effects exerted at the plasma membrane cannot be excluded. Apparently FCCP induces more effective loads than valinomycin on the energy balance of reticulocytes as reflected in phosphorylation levels of adenine nucleotides.
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology*; D004563:Electrochemistry; D004734:Energy Metabolism / Q000187:drug effects*; D066298:In Vitro Techniques; D008928:Mitochondria / Q000187:drug effects; D009570:Nitriles / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D011817:Rabbits; D012156:Reticulocytes / Q000187:drug effects* / Q000378:metabolism; D014634:Valinomycin / Q000494:pharmacology*
D009570:Nitriles; D014634:Valinomycin; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate