Neural regulation of cyclic AMP, cyclic AMP-dependent protein kinase, and phosphorylase in bullfrog ventricular myocardium.

The roles of cyclic AMP and cyclic AMP-dependent protein kinase in the contractile and metabolic responses to neural stimulation were studied in the bullfrog heart perfused in situ. The interaction of parasympathetic and sympathetic nerves in the regulation of myocardial cyclic AMP, cyclic AMP-dependent protein kinase, and phosphorylase also was studied. Stimulation of the left vagosympathetic trunk in the presence of atropine (10 JUM), i.e., sympathetic stimulation, caused frequency-dependent increases in ventricular contractility, cyclic AMP concentration, and activities of cyclic AMP-dependent protein kinase and phosphorylase. Maximal responses occurred with stimulation at frequencies of 5-20 Hz. Responses at 5 Hz persisted throughout 1 minute of continuous stimulation. In contrast, at 100 Hz, all responses except phosphorylase activation were transient during 1 minute of continuous stimulation. The frequencyand time-dependence of the cyclic AMP and cyclic AMP-dependent protein kinase responses were found to be very similar to those of the contractile response. These data are consistent with the hypothesis that cyclic AMP and cyclic AMP-dependent protein kinase serve as mediators of the sympathetic contractile response. All biochemical and mechanical responses to sympathetic neural stimulation were blocked by propranolol (1 JUM), suggesting that only /?-adrenergic receptors are involved in the sympathetic responses. In the absence of atropine, stimulation of the left vagosympathetic trunk had no effect on cyclic AMP concentration or the activities of cyclic AMP-dependent protein kinase and phosphorylase. Therefore, simultaneous parasympathetic stimulation totally blocked the sympathetic biochemical responses. This correlates with a total blockade of the sympathetic contractile response by simultaneous parasympathetic stimulation. Stimulation of the left vagosympathetic trunk in the presence of propranolol (without atropine), i.e., parasympathetic stimulation alone, had no significant effect on cyclic AMP concentration or the activities of cyclic AMP-dependent protein kinase and phosphorylase. (Circ Res 51: 551-559, 1982 )