On the nature of the stimulation by glucagon on citrulline synthesis in rat-liver mitochondria

Abstract

The stimulatory effect of glucagon on functions in liver mitochondria has been reviewed in [ 11. These functions include state-3 respiration, uncoupler-stimulated respiration, succinate dehydrogenase activity and pyruvate carboxylation. The stimulatory effect is observed in mitochondria isolated after treatment of intact rats, perfused livers or isolated liver cells with the hormone. The magnitude of the stimulation by glucagon was elegantly shown to be dependent on the medium used to isolate the mitochondria in [ 11. The effects of glucagon were found to be much smaller in mitochondria isolated in a medium with mannitol as osmotic support than in those isolated in a sucrosecontaining medium. This difference was mainly due to the fact that the rates of the functions measured in control mitochondria isolated in a mannitol medium were higher than the rates found when a sucrose-containing isolation medium was used. It was concluded [l] that glucagon treatment stabilises the mitochondrial membrane rather than activates mitochondrial functions. This conclusion is clearly valid for the functions investigated [ 11. It is therefore important to know whether this applies to other mitochondrial functions. We show here, that the stimulatory effect of glucagon on citrulline synthesis is due to an activation of carbamoyl-phosphate synthetase and, unlike the stimulatory effect of the hormone on the functions in [ 11, cannot be ascribed to effects on the stability of the mitochondrial membrane.