THE EFFECT OF INOTROPIC CATECHOLAMINES, CALCIUM AND AMINOPHYLLINE ON GLYCOGEN SYNTHETASE ACTIVITY IN THE INTACT CAT HEART

¹ Department of Pharmacology, State University of New York, Downstate Medical Center, Brooklyn, New York

Glycogen synthetase activity in the heart was determined after treatment of intact cats with cardiotonic agents in an attempt to test certain hypotheses : 1) whether, in the case of heart muscle, those agents which are known to produce a phosphorylase activation would have opposite, inactivating effects on glycogen synthetase activity, as has been shown in skeletal muscle; 2) whether increased force of contraction of the heart is accompanied by proportional changes in enzyme activity; and 3) whether the agents employed, which are known to produce increases in glucose-6-phosphate in the intact heart, would elicit in vivo the glucose-6-phosphate activation of glycogen synthetase which is seen in vitro. It was found that epinephrine, norepinephrine and isoproterenol significantly increased the active "I" form of synthetase; total activity was unaffected. The biochemical order of potency closely paralleled the known inotropic and glucose-6-phosphate-producing actions of the catecholamines, i.e., isoproterenol norepinephrine = epinephrine. Aminophylline produced a fall only in total enzyme activity. Calcium had no significant effect on enzyme activity. It was concluded that 1) activators of cardiac phosphorylase do not usually induce inhibition of glycogen synthetase in the heart and 2) although changes in glycogen synthetase activity may occur parallel with changes in cardiac muscle contractility and the in vivo augmentation of glucose-6-phosphate in the heart under certain conditions, a direct relationship does not obtain in all cases.