Abstract
It was reported previously (1) that an increase in heart phosphorylase a following the intravenous administration of adrenaline in a dose of 10.0 μg/kg was less than that following 1.0 μg/kg, and that atropinization or vagotomy potentiated the phosphorylaseactivating action of adrenaline. In addition, a significant elevation of heart phosphorylase a was maintained for 2 hours after the injection of 1.0 μg/kg of adrenaline. From the results, it was suggested that the reflectively released endogenous acetylcholine inhibited the phosphorylase-activating action of adrenaline, and that the long-lasting elevation of heart phosphorylase a even after disappearance of the positive inotropic action of adrenaline was related to the uptake or storage mechanism of adrenaline in the heart tissue.
Many investigators (2-6) demonstrated that the positive ino- and chrono-tropic responses to exogenous adrenaline of the heart were closely related to the activation of formation of cyclic 3', 5'-AMP with subsequent conversion of phosphorylase b to a. The finding (7) that injection of ganglionic stimulating agents such as DMPP and McNeil-A-343 produced an increase in heart phosphorylase a with concomitant hypertension and increase in cardiac contractile force may suggest a relationship between the level of circulating catecholamine endogenously liberated and the activity of phosphorylase in the heart. However, there are controversial reports regarding the effect of reserpine on heart phosphorylase activity: no significant change (4, 8), increase (6), and decrease (9). This is incompatible with the concept that there is a positive correlation between the amount of endogenous catecholamine and cardiac phosphorylase a activity.
The inhibitory effects of injected acetylcholine and vagal stimulation on the activity of heart phosphorylase a in open-chest rats have been demonstrated by Hess et al. (7). In an attempt to study the effect of endogenous acetylcholine on heart phosphorylase a, anticholinesterase agents were injected to spinal rats. Unexpectedly, physostigmine increased the activity of the heart enzyme. Further, combined administration of adrenaline and physostigmine, both of which otherwise activated the heart enzyme, resulted in an inhibition of the enzyme activity.
