cAMP-independent stimulation of glycogen phosphorylase in newborn rat hepatocytes.

Postnatal development of glycogen phosphorylase activation by the cAMP-independent pathway was examined in isolated rat hepatocytes from control and propylthiouracil-treated congenital hypothyroid rat pups. At 5 days postnatum there was complete phosphorylase activation by beta-adrenergic stimulation, glucagon, and the calcium ionophore A23187, but no activation by alpha-adrenergic stimulation. Activation of phosphorylase by angiotensin or vasopressin was less than in hepatocytes from adult rats (P less than 0.01). At 28 days postnatum activation by all of these hormones was complete. In the propylthiouracil-treated group hormone responsiveness was similar to the control at 5 days postnatum. However, alpha-adrenergic (P less than 0.025), angiotensin, and vasopressin (P less than 0.05) activation was decreased at 28 days postnatum, and beta-adrenergic, glucagon, and A23187 activation was complete. The attenuated responses were restored by thyroxine replacement from 15 days postnatum. [32P]Pi incorporation into phosphatidylinositol by epinephrine and vasopressin in 28-day propylthiouracil-treated rats was lower than the control (P less than 0.01). We speculate that the diminished phosphorylase response of hepatocytes to alpha-adrenergic, vasopressin, or angiotensin stimuli in the early neonatal period could be related to low receptor numbers and the weaker phosphoinositide response during this period. Also, the depressed phosphorylase response to alpha-adrenergic, vasopressin, and angiotensin stimulation in congenital hypothyroidism at 28 days postnatum could be related to a decrease in number of plasma membrane receptors for these agonists.