Ca(2+)-loading modulates potencies of cyclosporin A, Mg2+ and ADP to recouple permeabilized rat liver mitochondria.
We studied the relative potencies of cyclosporin A and endogenous effectors (Mg2+ and ADP) to recouple rat liver mitochondria permeabilized by different Ca(2+)-loading in a P(i)-containing medium. Recoupling efficiency of cyclosporin A dramatically decreased at high Ca(2+)-loading (approx. 100 nM of Ca2+/mg protein and more). Mitochondria permeabilized by high Ca2+ were recoupled with approximately equal efficiency by higher cyclosporin A concentrations or by adding 1-5 mM Mg2+ together with low concentrations of cyclosporin A while potentiating effect of ADP on the cyclosporin A recoupling potency was insignificant. Mg2+ ions at concentrations of 3 mM and higher also prevented the carboxyatractylate-induced reversion of cyclosporin A recoupling effect. The data point to competitive relationships between cyclosporin A and/or Mg2+ ions and Ca2+ ions for the site(s) regulating permeability state of the pore.
A.N. Belozersky Institute of Physico-Chemical Biology, M.V. Lomonosov Moscow State University, Russia.
Andreyev AYu
L M
LM
Mikhaylova
A A
AA
Starkov
Kushnareva YuE
D019297:2,4-Dinitrophenol; D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000818:Animals; D001278:Atractyloside / Q000031:analogs & derivatives / Q000494:pharmacology; D002122:Calcium Chloride / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology*; D004140:Dinitrophenols / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D008278:Magnesium Sulfate / Q000494:pharmacology*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D009861:Onium Compounds / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010539:Permeability; D051381:Rats
D004140:Dinitrophenols; D009861:Onium Compounds; D009943:Organophosphorus Compounds; D001278:Atractyloside; D004533:Egtazic Acid; D000244:Adenosine Diphosphate; D008278:Magnesium Sulfate; D016572:Cyclosporine; D000226:Mitochondrial ADP, ATP Translocases; D002122:Calcium Chloride; D019297:2,4-Dinitrophenol; C003853:carboxyatractyloside; C013289:tetraphenylphosphonium