Activation and inactivation of phosphorylase and glycogen synthetase during perfusion of rat liver as influenced by epinephrine, glucagon and hydrocortisone.

1. The changes in phosphorylase activity and glycogen synthetase I (active form) activity during perfusion of rat liver were studied together with their responses to added epinephrine and glucagon. 2. Phosphorylase activity of the liver from fed or fasted rats fell rapidly during perfusion, regardless of whether the perfusate was added with glucose or not. The addition of epinephrine or glucagon at the start or at 60 min of perfusion caused a prompt restoration of the initial high activity. Both glycogen breakdown and glucose liberation proceeded in parallel with the changes in phosphorylase activity. 3. The I-form of glycogen synthetase in the liver from fed rats increased rapidly when the concentration of perfusate glucose was raised to near 10 mM. This increase was promptly prevented by the addition of epinephrine or glucagon. In contrast, glycogen synthetase of the liver from fasted rats responded to neither glucose nor epinephrine (or glucagon) during perfusion. 4. Phosphorylase in the liver of fasted, adrenalectomized rats did not respond to a low concentration of epinephrine (3 - 10(-8) M) or glucagon (5 - 10(-9) M), but was increased by higher concentrations of the hormones. The treatment of adrenalectomized rats with hydrocortisone restored the response of liver phosphorylase to the low concentrations of the hormones. Thus, glucocorticoid plays a "permissive" role by increasing the affinity of liver phosphorylase to epinephrine or glucagon.