Evidence that cyclic AMP is not involved in the chronotropic action of glucagon in the adult mouse heart

The effects of glucagon on the adult mouse heart have been studied. Glucagon (1 mg/kg) increased heart rate in the adult mouse. This effect was enhanced in animals which had been pretreated with reserpine to deplete catecholamines. No change in the cardiac cyclic AMP concentration after the injection of glucagon was seen in the hearts of reserpinized animals. Moreover, adenylyl cyclase activity, measured in two different laboratories in whole homogenates, 600 × g pellets or washed particles from adult mouse hearts, was not activated by glucagon. Finally, the injection of epinephrine (1.6 mg/kg), but not of glucagon (1.0 mg/kg), increased the per cent of cardiac phosphorylase a activity and depleted cardiac glucogen. Since increased levels of cyclic AMP are associated with an increase in the per cent of the cardiac phosphorylase a activity, these experiments provide evidence for the hypothesis that cyclic AMP is not essential for the rate effects of glucagon in the adult mouse.