Insensitivity of cardiac phosphofructokinase to adrenergic activation in Zucker rats. A post-receptor defect.

The apparent insensitivity of phosphofructokinase to activation by adrenaline in hearts from genetically obese Zucker (fa/fa) rats [Patten, Filsell & Clark (1982) Metab. Clin. Exp. 31, 1137-1141] was examined in detail. Perfusion of hearts from obese (fa/fa) animals with medium containing 1nM-100 microM-adrenaline for 4 min did not significantly activate phosphofructokinase, but fully activated glycogen phosphorylase. Activation of phosphofructokinase occurred in hearts from lean (Fa/?) animals, with half-maximal activation at 10nM-adrenaline. Binding characteristics of cardiac alpha 1-adrenergic receptors were comparable between lean and obese animals. Properties of phosphofructokinase from obese and lean hearts were similar. High extracellular Ca2+ concentration, which activated phosphofructokinase in hearts from lean animals and phosphorylase in all hearts, failed to activate phosphofructokinase in hearts from obese rats. The data indicate that the failure of adrenaline to activate phosphofructokinase in hearts from obese (fa/fa) rats results from a post-receptor defect in the as-yet unidentified Ca2+-dependent phosphofructokinase-activating reactions.