Exogenous ATP antagonizes the actions of phospholipase A2, local anesthetics, Ca2+ ionophore A23187, and lithium on glucose-1,6-bisphosphate levels and the activities of phosphofructokinase and phosphoglucomutase in rat muscle

Abstract

ATP, added externally to the incubation medium of rat diaphragm muscles, abolished the decrease in the levels of glucose-1,6-bisphosphate (Glc-1,6-P2), the powerful regulator of carbohydrate metabolism, induced by phospholipase A2, local anesthetics, Ca2+ ionophore A23187, or lithium. Concomitantly to the changes in Glc-1,6-P2, the potent activator of phosphofructokinase (the rate-limiting enzyme in glycolysis) and phosphoglucomutase, the activities of these enzymes were reduced by the myotoxic agents and restored by exogenous ATP, when assayed under conditions in which these enzymes are sensitive to regulation by Glc-1,6-P2. These findings suggest that ATP may have broad therapeutic action, as it may stimulate the impaired glycolysis in muscle induced by various drugs and conditions which cause muscle weakness or damage.