The action of trialkyltin compounds on mitochondrial respiration. The effect of pH.
1. Inhibition of 2,4-dinitrophenol-stimulated respiration by trialkyltins is dependent on the presence of Cl(-) in the assay medium and is only apparent at acid pH values. It appears to be a result of the Cl(-)-OH(-) exchange mediated by trialkyltins. 2. In a KCl medium at alkaline pH values, the maximum rate of respiration produced by uncouplers is further increased by the presence of trialkyltins. 3. The inhibition of uncoupled succinate oxidation at acid pH values is not reversed by increasing the external substrate concentration, suggesting that depletion of intramitochondrial succinate is not an important factor in the inhibition. 4. It is suggested that the probable explanation for these observations is that in the presence of Cl(-) trialkyltins alter the internal pH to a more acid value and this directly affects the activity of one or more steps in succinate oxidation. 5. The oligomycin-like action of trialkyltins in a Cl(-)-free medium shows considerable pH-dependence over the pH range 6.6-7.6 in the presence of 10mm-phosphate, but very much less pH-dependence in the presence of 1mm-phosphate. 6. The binding of triethyltin to mitochondria shows a pK at pH6.3 and does not change greatly over the pH range 6.6-7.6. 7. It is suggested that the pH-dependence of the oligomycin-like action described by Coleman & Palmer (1971) is the result of the pH-dependence of the formation of a hydrophilic complex between trialkyltins and P(i).
D000818:Animals; D001665:Binding Sites; D002498:Centrifugation; D002712:Chlorides / Q000378:metabolism; D004140:Dinitrophenols / Q000494:pharmacology; D004579:Electron Transport; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007700:Kinetics; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D009942:Organometallic Compounds / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects*; D011485:Protein Binding; D011868:Radioisotopes; D051381:Rats; D013386:Succinates / Q000494:pharmacology; D014001:Tin / Q000494:pharmacology*
D002712:Chlorides; D004140:Dinitrophenols; D009942:Organometallic Compounds; D011868:Radioisotopes; D013386:Succinates; D014001:Tin