Cyclic adenosine monophosphate and cardiac contractility.

• This review examines critically the evidence bearing on the hypothesis that the positive inotropic effects of catecholamines are mediated by intracellular cyclic adenosine monophosphate (cyclic AMP). The review is selective in several respects. For example, it does not contain extensive discussions about the biochemical actions of cyclic AMP, the enzymes regulating its synthesis and degradation, or the role of cyclic AMP and other cyclic nucleotides as mediators of actions of drugs and hormones other than the catecholamines. Because of space limitations reference to many important investigations recently reviewed comprehensively (1-3) has been omitted. Cyclic AMP was discovered in the course of investigations of the effects of adrenergic agents on carbohydrate metabolism. Intracellular cyclic AMP concentrations are regulated by the activities of at least two enzymes: adenylate cyclase mediates synthesis of cyclic AMP, and cyclic nucleotide phosphodiesterase mediates its degradation. The concentration of free intracellular cyclic AMP might also be regulated by nonreceptor binding proteins that protect cyclic AMP from degradation but limit its access to its sites(s) of action. Cyclic AMP initiates a series of reactions that cause augmentation of glycogenolysis (Fig. 1) and lipolysis and inhibition of glycogen synthesis. The transformation of the enzyme, phosphorylase b, to the phosphorylated form, phosphorylase a, facilitates glycogen breakdown. Accordingly, transformation of phosphorylase b to phosphorylase a has been frequently used as an index of cyclic AMP effects in myocardial cells. However, transformation of