Increase in glucose 1,6-bisphosphate levels, activation of phosphofructokinase and phosphoglucomutase, and inhibition of glucose 1,6-bisphosphatase in muscle induced by trifluoperazine.
Injection of trifluoperazine (TFP) to rats induced a significant rise in the level of glucose 1,6-bisphosphate (Glc-1,6-P2) in muscle. This increase in Glc-1,6-P2, the potent activator of phosphofructokinase and phosphoglucomutase, was accompanied by a marked activation of both enzymes, when assayed in the absence of exogenous Glc-1,6-P2 under conditions in which these enzymes are sensitive to regulation by endogenous Glc-1,6-P2. Glucose-1,6-bisphosphatase (the enzyme that degrades Glc-1,6-P2) was markedly inhibited following the injection of TFP, which may account for the rise in the Glc-1,6-P2 level. Previous results from this laboratory have revealed that muscle damage or weakness is characterized by a decrease in Glc-1,6-P2 levels, leading to a marked reduction in the activities of phosphoglucomutase and phosphofructokinase (the rate-limiting enzyme in glycolysis). The present results suggest that TFP treatment may have a beneficial effect on the depressed glycolysis in muscle weakness or damage.
D000818:Animals; D019298:Glucose-6-Phosphate / Q000031:analogs & derivatives*; D005958:Glucosephosphates / Q000378:metabolism*; D006019:Glycolysis; D009132:Muscles / Q000187:drug effects / Q000201:enzymology*; D010732:Phosphofructokinase-1 / Q000378:metabolism*; D010733:Phosphoglucomutase / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D051381:Rats; D014268:Trifluoperazine / Q000494:pharmacology*
D005958:Glucosephosphates; D014268:Trifluoperazine; D019298:Glucose-6-Phosphate; C016473:glucose-1,6-bisphosphate; D010732:Phosphofructokinase-1; C014818:glucose 1,6-diphosphate phosphatase; D010744:Phosphoric Monoester Hydrolases; D010733:Phosphoglucomutase