Interaction of acetylcholine and epinephrine on heart cyclic AMP-dependent protein kinase

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Abstract
In the isolated perfused rat heart, epinephrine produced a rapid, concentration-dependent increase in cyclic (c)AMP, activation of cAMP-dependent protein kinase, activation of phosphorylase and increase in contractile force. At epinephrine concentrations of 1 .mu.M or less, acetylcholine antagonized all these .beta.-adrenergic effects and also increased cGMP levels. When used alone, acetylcholine produced a rapid elevation of cGMP and markedly diminished contractile force but did not significantly lower basal cAMP levels or cAMP-dependent protein kinase activity. Changes in cAMP-dependent protein kinase activity may explain the antagonism of epinephrine-induced activation of phosphorylase by acetylcholine, but cannot completely account for the inhibitory effect of the cholinergic agent on contractile force.