The effect of sodium salicylate on the ion and water content of isolated rat-liver mitochondria.

Previous investigations in this Laboratory (Hetzel, Charnock & Lander, 1959; Charnock, Lockett & Hetzel, 1962) have shown that the administration of therapeutic doses of salicylate drugs to both man and rats disturbs the normal electrolyte balance in addition to increasing the metabolic rate. The chronic administration of both sodium salicylate and potassium salicylate to rats produces a significant decrease in the intracellular K+ ion concentration in the livers of these animals (Charnock, Opit & Hetzel, 1961). A similar effect of sodium salicylate on isolated rat diaphragm has been reported by Manchester, Randle & Smith (1958). These workers noted that an isomer of sodium salicylate, sodiump-hydroxybenzoate, failed to exert this effect just as it fails to exert a number of other effects associated with the action of the salicylate drugs both in vivo and in vitro (Hetzel et al. 1959; Randle & Smith, 1958a, b; Segal & Blair, 1959; Packer, Austen & Knoblock, 1959; Andrews, 1960). The suggestion has been made that salicylates exert at least part of their metabolic effect in vivo by uncoupling oxidative-phosphorylation processes in mitochondria (Charnock, Opit & Hetzel, 1962; Smith, 1955; Smith, 1949). It was decided therefore to investigate a possible relationship between the uncouLpling phenomenon and the disturbance of the electrolyte balance by comparing the effect of salicylate and p-hydroxybenzoate on the movement of Na+ and K+ ions in isolated rat-liver mitochondria. To dissociate the effect of active metabolism observations were made at 00.