REGULATION OF CYCLIC NUCLEOTIDE LEVELS AND GLYCOGEN-PHOSPHORYLASE ACTIVITY BY ACETYLCHOLINE AND EPINEPHRINE IN PERFUSED RAT HEARTS

Abstract

Acetylcholine (ACh) produced a time and dose-dependent increase in cyclic[c]GMP levels in perfused rat hearts without any significant (P > .05) change in cAMP level or glycogen phosphorylase activity. Epinephrine produced a dose-dependent increase in both cAMP and phosphorylase activity but no significant (P > .05) change in cGMP levels. When ACh (10-6 M) was infused into hearts during the infusion of epinephrine (10-6 M), a time-dependent increase in cyclic GMP and decrease in cAMP occurred, both of which preceded a significant (P < .05) decrease in glycogen phosphorylase activity. In epinephrine-stimulated hearts. ACh produced a dose-dependent increase in cGMP levels. Similar concentrations decreased cAMP levels and phosphorylase activity. No condition tested resulted in a significant (P > .05) change in glycogen synthase activity. ACh can reduce cAMP levels and phosphorylase activity only when they have been elevated above basal values. These changes are associated with an increase in cGMP. The reduction in phosphorylase produced by ACh may be the result of either or both of the changes in cyclic nucleotide levels.