PT - JOURNAL ARTICLE AU - G. A. ROBISON AU - R. W. BUTCHER AU - I. ØYE AU - H. E. MORGAN AU - E. W. SUTHERLAND TI - The Effect of Epinephrine on Adenosine 3',5'-Phosphate Levels in the Isolated Perfused Rat Heart DP - 1965 Sep 01 TA - Molecular Pharmacology PG - 168--177 VI - 1 IP - 2 4099 - http://molpharm.aspetjournals.org/content/1/2/168.short 4100 - http://molpharm.aspetjournals.org/content/1/2/168.full SO - Mol Pharmacol1965 Sep 01; 1 AB - The effect of epinephrine on cyclic AMP levels, phosphorylase activity, glycogen synthetase activity, and myocardial contractility was studied using the isolated perfused working rat heart. A single dose of epinephrine increased the level of cyclic AMP from 0.42 to 1.42 mµmoles/g within 3 sec of its administration, after which it rapidly declined toward the control level. The force of contraction meanwhile rose to 137% of its control value, but did not reach this peak until 20 sec after the injection. The phosphorylase a activity increased from an apparent value of 18.7% of total phosphorylase activity to 66.0%, but required 45 sec to obtain this maximum. No change in the glycogen synthetase activity could be detected. Nethalide blocked the epinephrine-induced rise in the cyclic AMP concentration as well as the inotropic effect. N-Isopropylmethoxamine did not block either of these effects. It was suggested that epinephrine acts first on the membrane adenyl cyclase system to increase the rate of formation of cyclic AMP, which then in turn acts as a second messenger to initiate the inotropic response. It was not possible to elicit a positive inotropic effect with cyclic AMP or several of its derivatives. Evidence was presented to show that cyclic AMP, when added to the perfusate, does not gain access to the intracellular fluid in concentrations comparable to those seen after the administration of epinephrine. ACKNOWLEDGMENT The authors would like to acknowledge the excellent technical assistance of Christine Baird and Joseph Campbell. These investigations were supported by grants from the National Institutes of Health of the U.S. Public Health Service (grants HE 08332 and AM 07642-01 AMP).