Effects of glucagon and N6O2′-dibutyryladenosine 3′:5′-cyclic monophosphate on calcium transport in isolated rat liver mitochondria

Abstract

Glucagon administration to fed rats by i.p. injection, or the perfusion of livers from fed rats with glucagon by the method of Mortimore was associated with increases of 15- and 5-fold respectively, in the time for which a given load of exogenous Ca2+ is retained by mitochondria subsequently isolated from the liver. This effect of glucagon was also induced by N6O2''-dibutyryl cyclic AMP, completely blocked by cycloheximide, relatively slow in onset (15-60 min) and associated with a stimulation of about 20% in the rates of ADP-stimulated O2 utilization and Ca2+ transport measured in the presence of succinate. Perfusion of livers with glucagon resulted in the isolation of mitochondria which showed a 50% increase, no significant change and a 40% increase in the concentrations of endogenous Ca, Mg and Pi, respectively, when compared with mitochondria isolated from control perfused livers. The administration of insulin or adrenaline [epinephrine] to fed rats induced increases of 10- and 8-fold respectively, in the time for which Ca2+ is retained by isolated liver mitochondria. Perfusion of livers with insulin had no effect on mitochondrial Ca2+ retention time. The perfusion of livers from starved rats with glucagon, or the administration of either glucagon or insulin to starved rats, increased by about 2.5- and 15-fold respectively, the time for which isolated mitochondrial retain Ca2+. Mechanisms which may be responsible for the observed alterations in Ca2+-retention time are discussed.