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

1978; American Physical Society; Volume: 234; Issue: 4 Linguagem: Inglês

10.1152/ajpheart.1978.234.4.h432

1522-1539

S L Keely, Thomas Lincoln, Jackie D. Corbin,

Receptor Mechanisms and Signaling

In the isolated perfused rat heart, epinephrine produced a rapid, concentration-dependent increase in cyclic adenosine 3',5'-monophosphate (cAMP), activation of cAMP-dependent protein kinase, activation of phosphorylase, and increase in contractile force. At epinephrine concentrations of 1 micron or less, acetylcholine antagonized all these beta-adrenergic effects and also increased cyclic guanosine 3',5'-monophosphate (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. The data suggest that changes in cAMP-dependent protein kinase activity can 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.