Adrenoceptor-mediated activation of liver glycogen phosphorylase: effects of thyroid state

Abstract

The effects of altered thyroid state on the adrenergic activation of rat liver glycogen phosphorylase were studied in hepatocytes isolated from normal, thyroidectomized and thyroxine-treated rats. Basal phosphorylase a activity was similar in the three groups. In normal rats, the order of potency of agonists was adrenaline > phenylephrine > isoproterenol, and the effect of adrenaline was blocked by dihydroergocryptine (10 −5M) or phenoxybenzamine (10 −5M) but not by propranolol (10 −5M). These results indicate that in the normal rat activation of this enzyme occurs via α-adrenoceptors. Thyroxine treatment increased sensitivity to all three agonists but did not change their relative potencies. Thyroidectomy dramatically altered the pattern of activation by agonists so that the order of potency now was isoproterenol > adrenaline > phenylephrine and activation by adrenaline was inhibited only by propranolol and not by α-antagonists. Activation of phosphorylase was now mediated via β-adrenoceptors. The effect of thyroidectomy on the adrenoceptor response pattern of the liver develops slowly (more than 2 weeks) and is opposite to the shift from β to α previously observed in the heart. (Br. J. Pharmacol. 59:177, 1977). These findings indicate that hypothyroidism in rats changes activation of liver glycogen phosphorylase from α to a β- type response and that the direction of thyroid-dependent changes in receptor balance is tissue-dependent.