The effect of salicylate on adenosine-triphosphatase activity of rat-liver mitochondria

Abstract

The adenosine-triphosphatase-activity patterns of fresh and aged rat-liver mitochondria were different at pH 6.3, 74, 8.5 and 9.4. Maximum activity was at pH 9.4 in fresh, but at pH 8.5 in aged mitochondria. It is suggested that the different activities found in fresh mitochondria with changing pH are at least in part due to changes in the permeability of the mitochondria to adenosine tri-phosphate. 2,4-Dinitrophenol (0-1 mM) greatly stimulated the adenosine-triphosphatase activity of fresh mitochondria in the absence of Mg2+ ions. This effect decreased with increasing pH. With aged mitochondria in the absence of Mg2+ ions, the effect of 2,4-dinitrophenol was reduced, but here the stimulation increased with increasing pH. Sodium salicylate (5 mM) stimulated adenosine-triphosphatase activity in fresh mitochondria only. As with the effect with 2,4-dinitrophenol, maximum activation occurred at pH 6.3, least at pH 9.4. This activation is separate from that produced by Mg2+ ion (mM) and is cumulative with it. Sodium salicylate (5 mM) did not effect the adenosine-triphosphatase activity of aged mitochondria, which showed much enhancement of activity by Mg2+ ions. Salicylate produced some inhibition of the Mg2+-ion-stimulated adenosine-triphosphatase activity of aged mitochondria. Mitochondria from salicylate-poisoned rats showed the same pattern of adenosine-triphosphatase activity at four pH values, and the same degree of efficiency of oxidative phosphorylation, as that found with mitochondria from untreated rats. Because stimulation by salicylate of adenosine-triphosphatase activity occurs only with fresh mitochondria, it is suggested that the mitochondrial "membrane" is the site of salicylate action. An increase in the permeability of this membrane to adenosine triphoephate in the presence of salicylate could explain the stimulation of adenosine-triphosphatase activity by this drug in vitro.