Effects of gramine on energy metabolism of rat and bovine mitochondria

The indole alkaloid gramine is found in several plant families. Its effects on mammalian mitochondria and submitochondrial particles were studied. Low concentrations of gramine slightly stimulated basal electron transport, totally inhibited the Ca 2+-induced respiratory control and partially abolished the enhancement of 8-anilino-1-naphthalene sulfonate fluorescence induced by proton translocation coupled to ATP hydrolysis or to succinate oxidation. At higher concentrations gramine inhibited specifically the electron transport at the level of Complex I of the respiratory chain. The I 50 values (2–6 mM) were dependent on the presence of uncouplers. Higher concentrations of the alkaloid also inhibited coupled succinate oxidation and ATP hydrolysis (I 50 = 10 mM). Possible explanations for these effects are discussed.