The role of cyclic AMP-mediated regulation of glycogen metabolism in levamisole-perfused Ascaris suum muscle.

The effects of levamisole on muscle contraction and glycogen metabolism have been examined in isolated muscle-cuticle sections of the roundworm Ascaris suum. Muscle contraction occurred when various levels of levamisole were perfused through the preparation. At a levamisole concentration of 0.42 mM, the period of contraction lasted only about 6 min and was followed by a period of relaxation. During this relaxation period, there was an activation of glycogen synthase (EC 2.4.1.11), as evidenced by a decrease in the Ka values of glucose 6-phosphate for glycogen synthase to 0.26 mM from control values of 0.50 mM. The glycogen phosphorylase (EC 2.4.1.1) activity ratio decreased from 0.85 to 0.65, which indicated an inactivation of this enzyme. Concomitant with this activation of glycogen synthase and inactivation of phosphorylase there was an increased synthesis of glycogen. In addition, the presence of levamisole prevented both the serotonin-induced cyclic AMP accumulation and the activation of the cyclic AMP-dependent protein kinase (EC 2.7.1.37). However, levamisole did not significantly affect the changes in glycogen synthase and phosphorylase brought about by perfusion with the neurostimulator acetylcholine. Collectively, the data indicated that levamisole caused a transient muscle contraction followed by muscle relaxation, and the muscle relaxation effect appeared to be the result of a levamisole-inhibited cyclic AMP-mediated pathway of glycogen utilization.