CAMP-MEDIATED AND NON-cAMP-MEDIATED HORMONAL CONTROL OF LIVER GLYCOGENOLYSIS

Abstract

Glucagon at physiological concentrations rapidly activates phosphorylase and glucose release in isolated rat liver parenchymal cells. The changes in these parameters are well correlated with accumulation of cAMP and activation of cAMP-dependent protein kinase with respect to time course and hormone concentration. The data support the view that cAMP is the sole mediator of glucagon action on hepatic glycogenolysis. Epinephrine at supraphysiological concentrations causes transient accumulation of cAMP and activation of protein kinase and phosphorylase in hepatocytes. Abolition of the cAMP increase with β-adrenergic blockers prevents the activation of protein kinase, but does not diminish the rise in phosphorylase a. However, α-adrenergic blockade greatly diminishes phosphorylase a without affecting cAMP accumulation or protein kinase activation. The data thus indicate that the actions of epinephrine on hepatic glycogen metabolism largely involve α-adrenergic receptors and that the β-adrenergic-cAMP system plays a minor role. Consistent with these findings, the α-adrenergic agonist phenylephrine activates phosphorylase and glucose release in hepatocytes without increasing cAMP or activating cAMP-dependent protein kinase.