Abstract

This paper describes the kinetics of the changes in the levels of the glycolytic intermediates, phosphorylase a, cyclic AMP, creatine phosphate, the adenine nucleotides, and inorganic phosphate in isolated perfused rat hearts following the administration of epinephrine.

Cyclic AMP, ADP, AMP, creatine and inorganic phosphate, all increased monotonically from the onset of the contractile force increase. Cyclic AMP levels reached peak values after about 10 sec, and maximum values of ADP, AMP, creatine, and inorganic phosphate were observed after about 25 sec. The increases of ADP and AMP were stoichiometrically accounted for by a fall in ATP, and the increases of creatine and inorganic phosphate by a fall in creatine phosphate. Phosphorylase a activity increased by 60% and reached a broad peak after 20-30 seconds. This increase occurred a few seconds after the onset of the inotropic response. The tissue levels of all the glycolytic intermediates also increased transiently, there being a 10-15 sec delay relative to the inotropic response. These results demonstrate transient effect of cyclic AMP on the phosphorylase system, and the temporal separation of the inotropic and glycogenolytic effects of epinephrine.

Control sites in the utilization of glucose and glycogen have been identified at the steps of glucose penetration into the cell, hexokinase, phosphofructokinase, and at an enzymic site between glyceraldehyde-3-P and 3-P glyceric acid. The rate of intracellular glucose and glycogen utilization appears to be controlled principally by the activities of phosphorylase and phosphofructokinase. Measurement of the complete pattern of glycolytic intermediates during the period of rapid glycogenolysis induced by epinephrine has permitted an analysis of the control exerted at the phosphofructokinase site due to changes in the tissue content of adenine nucleotides, inorganic phosphate, and cyclic AMP.