Role of cyclic AMP in the actions of catecholamines on hepatic carbohydrate metabolism

Abstract

Studies using perfused rat liver and isolated liver parenchymal cells show that low concentrations of epinephrine, norepinephrine, and phenylephrine can activate glycogenolysis and gluconeogenesis by a mechanism mediated by alpha-adrenergic receptors and not involving accumulation of cAMP. The glycogenolytic and gluconeogenic activites of epinephrine, norepinephrine, and phenylephrine are inhibited by the alpha-adrenergic receptor antagonists phentolamine and dihydroergotamine, but are negligibly affected by the beta-adrenergic receptor antagonist propranolol. Epinephrine, norephinephrine, and the beta-adrenergic receptor agonists isoproterenol, soterenol, and salbutamol increase cAMP accumulation; and this effect is antagonized by propranolol. Isoproterenol, soterenol, and salbutamol activate glycogenolysis and gluconeogenesis, but are less effective than epinephrine or norepinephrine. The data are interpreted as indicating the existence of both alpha- and beta-adrenergic receptors in rat liver. Activation of the alpha-adrenergic mechanism appears to be more important than the beta-adrenergic receptor-cAMP system in the physiologic effects of epinephrine and norepinephrine on carbohydrate metabolism in rat liver.