Abstract

Diaphragm muscles from Sherman rats were incubated in Krebs-Ringer phosphate buffer at pH 7.4 and a concentration of either 100 or 200 mg/100 ml glucose. In the presence of ouabain (10^-4M) there were increased glucose uptake and glycogen content of muscle and a decreased lactate production combined with an increased. pyruvate concentration in the medium. In some experiments, C¹⁴-labeled glucose was added to the medium. During incubation with ouabain, the production of C¹⁴O₂ from glucose was lower than in control, while O₂ consumption was not changed. In the presence of ouabain, there was an accumulation of glucose-6-phosphate and fructose-6-phosphate and a decrease of fructose-1, 6-diphosphate. However, there was no accumulation of glucose-6-phosphate and fructose-6-phosphate when glucose was omitted from the medium. When twice the amount of phosphate was used in the medium, the effect of a similar dose of ouabain on lactate production and glycogen content was much less than that observed in medium containing the normal concentration of phosphate. Similar changes in glucose uptake, glycogen content of muscle and lactate and pyruvate production were observed with digitoxin (10^-5 M). When glycolysis and glycogenolysis were stimulated by epinephrine (10^-5M), norepinephrine (10^-5M) or the dibutyryl derivative of cyclic 3',5'-adenosine monophosphate (10^-3 M), digitoxin (10^-5 M) inhibited the effects of these drugs on glycogen breakdown and lactate production. These findings indicate that phosphofructokinase and phosphorylase are involved in the inhibition of the glycolytic pathway caused by these concentrations of cardiac glycosides.