Reexamination of the Second Messenger Hypothesis of Glucagon and Catecholamine Action in Liver

Abstract

Glucagon causes a rapid activation of cAMP-dependent protein kinase in rat liver parenchymal cells which correlates well with the accumulation of cAMP. Full activation of phosphorylase or inactivation of glycogen synthase is achieved with half-maximal activation of protein kinase. Epinephrine stimulates glycogen breakdown and gluconeogenesis in these cells mainly by mechanisms involving α-adrenergic receptors and not β-receptors. Activation of α-receptors results in rapid activation of phosphorylase and inactivation of glycogen synthase without accumulation of cAMP or activation of cAMP-dependent protein kinase. Activation of β-receptors causes a transient rise in cAMP and a short-lived activation of protein kinase with correspondingly little stimulation of glycogenolysis and gluconeogenesis.