INACTIVATION OF HEPATIC ACETYL-COA CARBOXYLASE BY CATECHOLAMINE AND ITS AGONISTS THROUGH THE ALPHA-ADRENERGIC RECEPTORS

The effects of adrenergic agonists on acetyl-CoA carboxylase and fatty acid synthesis were studied in isolated rat hepatocytes from mature rats (300-350 g). Norepinephrine and phenylephrine inactivate acetyl-CoA carboxylase activity and inhibit fatty acid synthesis. The effects of both norepinephrine and phenylephrine were blocked by the .alpha.-adrenergic receptor blockers, phentolamine and phenoxybenzamine, and unaffected by the .beta.-receptor blocker propranolol. This inactivation was not mimicked by the .beta.-agonist isoproterenol. The measurable increase in cAMP levels caused by norepinephrine and phenylephrine was abolished by the .alpha.-antagonist phentolamine and diminished by the .beta.-antagonist propranolol. Ca depletion potentiated the increase in cAMP levels by phenylephrine but abolished the phenylephrine inactivation of the carboxylase. The inactivation of acetyl-CoA carboxylase by phenylephrine was correlated with an increase in the incorporation of [32P]phosphate into the enzyme. Catecholamines and their agonists promote phosphorylation and inactivation of acetyl-CoA carboxylase through the .alpha.-adrenergic receptor, and the inactivation requires Ca.