Adenyl cyclase and cyclic AMP. Biochemical links in the regulation of myocardial contractility.

The actions of many hormones may be related to their capacity to increase adenyl cyclase activity in their target organs. The evidence indicating that catecholamines and glucagon augment myocardial contractility by enhancing the activity of myocardial adenyl cyclase is summarized. Furthermore, data are presented suggesting that the inotropic actions of epinephrine and glucagon ultimately may be due to an increase in sarcotubular calcium stores, an effect that appears to be related to activation of an adenyl cyclase pool localized in the sarcoplasmic reticulum. Other hormones that may alter contractility through actions on the adenyl cyclase-cyclic AMP system are thyroid hormone, histamine, prostaglandin, and acetylcholine. Chronic cardiac decompensation in both the experimental animal and in man diminishes the effectiveness of glucagon as an inotropic agent and interferes with the mechanisms by which glucagon acts to enhance the activity of myocardial adenyl cyclase, changes that may be causally interrelated. Although an understanding of the adenyl cyclase system would seem to be extremely important for an understanding of the basic mechanisms responsible for modulating the intensity of the contractile state of the heart, further investigations are necessary for complete validation of this hypothesis.