PROGRESSIVE WEAKENING OF THE RESPONSE OF KEY ENZYMES OF LIVER-GLYCOGEN METABOLISM TO PERMANENTLY INCREASED PLASMA EPINEPHRINE LEVELS

In adult male rats anaesthetized and pentobarbital the intravenous infusion at 0.5 .mu.g .cntdot. kg-1 .cntdot. min-1 of epinephrine increased liver phosphorylase a activity within 5 min, whereas later a weakening of the hormone effect was observed. After increasing the infusion rate to 1.0 .mu.g .cntdot. kg-1 .cntdot. min-1 and extending the study to more parameters, the diminishing effect on phosphorylase was confirmed and a similar response was established for liver cAMP. Concomitantly, a decrease and recovery of liver glycogen synthase a activity was observed. In rats with permanent catheters in one of their tail arteries for obtaining blood samples, the plasma epinephrine levels were shown to be permanently increased (from cca 1 pmol .cntdot. ml-1 before infusion of 1.0 .mu.g .cntdot. kg-1 .cntdot. min-1 to more than 30 pmol .cntdot. ml-1 during infusion) and remained at steady levels throughout the infusion. Therefore, the weakening of the epinephrine effect should be ascribed to changes at (or beyond) the catecholanine receptor level. A hitherto undescribed decrease of total glycogen synthase activity was observed during the infusions.