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 (original) (raw)

1987, Biochemical Medicine and Metabolic Biology

Experiments in our laboratories as well as in those of others have revealed that glucose 1,6-bisphosphate (Glc-1,6-P*) is a powerful regulator of carbohydrate metabolism (for reviews, see Refs. l-3). The unique feature of Glc-1,6-P, is that it acts as an intracellular signal which controls the activities of several key enzymes in carbohydrate metabolism. Its intracellular concentration is controlled by different physiological and pathological conditions, leading to concomitant changes in the activities of the key enzymes which are modulated by this regulator. The intracellular levels of Glc-1,6-P* are controlled by cyclic nucleotides (4-6) and by Ca*+ (6,7). Glc-l,6-P2 was found to be involved in the mechanism of action of several hormones and pharmacologic agents (4,6,8-13). Its concentration also changes during starvation (14), anoxia, or ischemia (15,16), during differentiation (6) and growth (17-19), and in senescence (20). The intracellular levels of Glc-1,6-P, in muscle are markedly decreased in muscular dystrophy (14,21,22), as well as by treatment of normal muscle with phospholipase A2 (23), local anesthetics (lo), Ca*+ ionophore A23187 (7) and lithium (ll), leading to a marked reduction in glycolysis. All these compounds are known to induce muscle damage or weakness similar to that occurring in muscular dystrophy (24-29). ATP is a drug used in the therapy of myopathies ("Adenotriphos," Rona, UK). The mechanism of action of ATP is not known.