Bépridil a new effector of oxidative phosphorylations.

Bépridil action on oxidative phosphorylations depends on the nature of the oxidized substrate. Thus it seemed to act as an uncoupler on the FAD-linked substrates as we have shown with succinate. But this property could not be applied to the NAD-linked substrates. Thus, in the presence of Bépridil, ADP would have opposite effects on the electron flow across the first site of oxidative phosphorylations; from one side the direct electron flow was decreased while from the other side, the reverse one was increased. Confirming this difference in its action, Bépridil did not affect the oxidative phosphorylation property of the cytochrome oxidase as could be deduced from the invariability of TMPD + ascorbate oxidation whether Bépridil was added or not. Moreover the effect of Bépridil on the P/O ratio was a dramatic demonstration of its selectivity. As a matter of fact this ratio was increased to a value near 5 for the NAD-linked substrate while it was decreased to near 0.4 with the FAD-linked substrate.