Adrenergic control of glycolysis and pyruvate kinase activity in hepatocytes from young and old rats.

The influence of various adrenergic agonists and antagonists on pyruvate kinase activity and lactate production from endogenous glycogen reserves was investigated in hepatocytes isolated from young and old rats. With hepatocytes prepared fromjuvenile rats (100 to 150 g) 10 PM epinephrine and 10 pM isoproterenol (a padrenergic agonist) inhibit pyruvate kinase activity and lactate production; whereas, 10 pM phenylephrine (an cu-adrenergic agonist) has no influence on either parameter. With hepatocytes from fully mature adults (300 g and up) epinephrine, isoproterenol, and phenylephrine are all without influence on lactate production from endogenous glycogen reserves. Epinephrine gives a small but reproducible inhibition of pyruvate kinase activity in hepatocytes from adult rats, but isoproterenol and phenylephrine have no significant influence on the enzyme activity. In the presence of 0.5 mM theophylline, epinephrine and phenylephrine give a significant inhibition of pyruvate kinase activity and lactate production, with hepatocytes from both young and adult rats. Theophylline alone has no significant influence on pyruvate kinase activity, but it does give approximately 20% inhibition of lactate production in hepatocytes from both young and old rats. The results of this investigation demonstrate that selective changes in the metabolic response of the hepatocyte to various adrenergic agonists occur as the rat matures; however, similar changes are not observed with glucagon. The selective changes in the metabolic response of the hepatocyte appear to be related to changes in the adrenergic receptor system which occur during development.