Effect of Beta-Adrenergic Stimulation on Myocardial Adenine Nucleotide Metabolism

The effects of isoproterenol, propranolol, and compound D600 (α-isopropyl-α-[(N-methyl-N-homoveratryl)-γ-aminopropyl1–3, 4, 5-trimethoxyphenylacetonitrile) on myocardial adenine nucleotide metabolism were studied in rat hearts in situ. Isoproterenol in doses between 0.1 and 25 mg/kg induced an increase in heart rate concomitant with a significant acceleration in the de novo synthesis of adenine nucleotides (ATP, ADP, and AMP) and a diminution in their concentration. The effects of isoproterenol were antagonized by propranolol (1 and 50 mg/kg), which alone caused a reduction in the de novo synthesis of adenine nucleotides without inducing a change in their concentration. Compound D600 (10 mg/kg) brought about a slight elevation in the concentration of adenine nucleotides but did not influence the rate of de novo synthesis. The isoproterenol-induced diminution in adenine nucleotide concentration was prevented by D600; under these conditions, the acceleration of de novo synthesis was attenuated. These findings indicate that de novo synthesis of myocardial adenine nucleotides in the normal and the isoproterenol-stimulated heart is regulated not only by a feedback mechanism dependent on the concentration of adenine nucleotides but also by β-receptor-mediated alterations in carbohydrate metabolism which can cause changes in the size of the available pool of 5-phosphoribosyl-1-pyrophosphate.