The effect of levamisole on glycogen synthase and the metabolism of Litomosoides carinii.

The effects of the anthelmintic drug, levamisole, on glycogen metabolism in the adult filariid, Litomosoides carinii, were examined. Incubation of helminths for up to 6 hr in the presence of levamisole resulted in a fourfold increase in total worm glycogen levels. In accord with this observation, levamisole also produced an eightfold increase in the rate of incorporation of [14C]-glucose into [14C]-glycogen over a 6-hr incubation period. In contrast, levamisole had no significant effect on 14CO2 evolution or lactate formation from exogenous glucose indicating that glycolysis was not affected. Because levamisole stimulated the incorporation of [14C]-glucose into glycogen, its effects on glycogen synthase activity were determined. Glycogen synthase in L. carinii was found to exist in both glucose-6-phosphate dependent (D) and glucose-6-phosphate independent (I) forms. In vitro incubation of intact L. carinii for 2 hr in the presence of levamisole resulted in a significant increase in the activity ratio (activity in the absence of glucose-6-P divided by the activity in the presence of glucose-6-P). This suggests that levamisole may act to stimulate the conversion of the less active (D) form of the glycogen synthase to the more active (I) form.