Molecular Pharmacology, Vol 4, 61-69, Copyright © 1968 by the American Society for Pharmacology and Experimental Therapeutics

Effects of Epinephrine on Cardiac Cyclic 3',5'-AMP, Phosphorylase Kinase, and Phosphorylase

¹ Department of Pharmacology, Division of Basic Health Sciences, Emory University Atlanta, Georgia 30322

The concentration of cyclic 3',5'-adenosine monophosphate (cyclic AMP) and the activities of phosphorylase kinase and phosphorylase were determined in biopsy samples from dog hearts and in whole rat hearts frozen in situ. Cyclic AMP was measured by the activation of muscle phosphorylase kinase employing a preincubation at 0° to improve the sensitivity of the assay. Dog heart phosphorylase kinase was measured on extracts of homogenates by comparing the activity of the enzyme at pH 6.0 to that at 8.2. Epinephrine markedly increased the activity at pH 6.0 at a dose that did not significantly elevate the percentage of phosphorylase . The time course of the change in kinase activity was consistent with the hypothesis that activation of this enzyme was necessary for time formation of cardiac phosphorylase .

No significant increase in the concentration of cyclic AMP was demonstrable in the dog heart at a dose of epinephrine that produced a marked inotropic effect. The possibility of an artifact in the biopsy technique was suggested by the finding that a rapid increase in cyclic AMP occurred in rat hearts frozen in situ, but not when samples were excised and frozen. Phosphorylase kinase activity increased as rapidly as did the cyclic AMP concentration and before any change in the phosphorylase activity occurred. Pronethalol blocked the epinephrine-induced rise in the cyclic AMP concentration.

These results are consistent with the hypothesis that the effect of catecholamines on cardiac phosphorylase is mediated through an action of cyclic AMP on phosphorylase kinase.

Note:
ACKNOWLEDGMENTS The authors wish to thank Mrs. Margaret Maltbie for her excellent technical assistance. This study was supported by Research Grant HE 04626 from the National Heart Institute, Career Development Award GM 6257 (S.E.M.), and the Interdepartmental Cardiovascular Training Program of Emory University School of Medicine sponsored by the National Heart Institute Training Grant 5T1 HE 5380.

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