Effects of inhibitors of platelets aggregation on oxidative phosphorylation in rat liver mitochondria in vitro.

The effects of inhibitors of platelets aggregation used in clinical practice (nicergoline, sulphinpyrazone, dipyridamole and aspirin) on respiration and phosphorylation of rat liver mitochondria in vitro are investigated. All the drugs studied, except aspirin, act as “inhibitors-uncouplers” in a same concentration range, 50–300 nmol/mg protein: they stimulate state 4 respiration, inhibit simultaneously state 3 oxidation (inhibition not reversed by 2–4 dinitrophenol), reduce the ADP/O ratio and respiratory control index (RCI) and stimulate the latent ATPase activity. The latest stimulation is inhibited by oligomycin 6 μg/mg protein. In presence of 200–800 nmol of aspirin/mg protein, the state 3 oxidation is only inhibited with succinate as substrate; aspirin would be a DNP-like uncoupler. It is observed that Triton X 100 acts in the same qualitative way and some similarities are suggested between inhibitors of platelets aggregation and detergents. Correlation between anti-aggregating properties and drug effects on mitochondrial functions are discussed.