Interaction of acetylcholine and epinephrine on heart cyclic AMP-dependent protein kinase.
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.
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004837:Epinephrine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D010477:Perfusion; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats
D000242:Cyclic AMP; D011494:Protein Kinases; D006152:Cyclic GMP; D000109:Acetylcholine; D004837:Epinephrine