title: Biochemical effects of the hypoglycaemic compound diphenyleneiodonnium. Catalysis of anion-hydroxyl ion exchange across the inner membrane of rat liver mitochondria and effects on oxygen uptake.
abstract: 1. The hypoglycaemic compound diphenyleneiodonium causes rapid and extensive swelling of rat liver mitochondria suspended in 150mm-NH(4)Cl, and in 150mm-KCl in the presence of 2,4-dinitrophenol and valinomycin. This indicates that diphenyleneiodonium catalyses a compulsory exchange of OH(-) for Cl(-) across the mitochondrial inner membrane. Br(-) and SCN(-) were the only other anions found whose exchange for OH(-) is catalysed by diphenyleneiodonium. 2. Diphenyleneiodonium inhibited state 3 respiration of mitochondria and slightly stimulated state 4 respiration with succinate or glutamate as substrate in a standard Cl(-)-containing medium. 3. Diphenyleneiodonium did not inhibit state 3 respiration significantly in two Cl(-)-free media (based on glycerol 2-phosphate or sucrose) but caused some stimulation of state 4. 4. In Cl(-)-containing medium diphenyleneiodonium only slightly inhibited the 2,4-dinitrophenol-stimulated adenosine triphosphatase and it had little effect in the absence of Cl(-). 5. The inhibition of respiration in the presence of Cl(-) is dependent on the Cl(-)-OH(-) exchange. 2,4-Dichlorodiphenyleneiodonium is ten times as active as diphenyleneiodonium both in causing swelling of mitochondria suspended in 150mm-NH(4)Cl and in inhibiting state 3 respiration in Cl(-)-containing medium. Indirect evidence suggests that the Cl(-)-OH(-) exchange impairs the rate of uptake of substrate anions. 6. It is proposed that stimulation of state 4 respiration in the absence of Cl(-) depends, at least in part, on an electrogenic uptake of diphenyleneiodonium cations. 7. Tripropyl-lead acetate, methylmercuric iodide and nine substituted diphenyleneiodonium derivatives also catalyse Cl(-)-OH(-) exchange across the mitochondrial membrane. 8. Diphenyleneiodonium is compared with the trialkyltin compounds, which are also known to mediate Cl(-)-OH(-) exchange and which have in addition strong oligomycin-like effects on respiration. It is concluded that diphenyleneiodonium is specific for catalysing anion-OH(-) exchange and will be a useful reagent for investigating membrane-dependent systems.
mesh_terms: D000085:Acetates / Q000494:pharmacology; D000251:Adenosine Triphosphatases; D000818:Animals; D001965:Bromides / Q000378:metabolism; D002384:Catalysis; D002712:Chlorides / Q000378:metabolism; D066298:In Vitro Techniques; D007455:Iodine / Q000494:pharmacology*; D007474:Ion Exchange; D007854:Lead / Q000494:pharmacology; D008566:Membranes / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D009942:Organometallic Compounds / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D051381:Rats
chemical_list: D000085:Acetates; D001965:Bromides; D002712:Chlorides; D009942:Organometallic Compounds; D000644:Quaternary Ammonium Compounds; D007854:Lead; D007455:Iodine; D000251:Adenosine Triphosphatases