Effect of glycogenolytic agents on glycogen synthase activity in polymorphonuclear leukocytes. Evidence for a Ca2+-mediated regulation of glycogen synthase activity.
Human polymorphonuclear leukocytes were found to respond to the beta-receptor activators, adrenalin and isoproterenol, with a rapid transient increase in cyclic AMP, activation of cyclic AMP-dependent protein kinase, phosphorylase kinase, deactivation of glycogen synthase and glycogen breakdown. This response was unaffected by the presence of 10 mM EGTA. Incubation of leukocytes with phorbol myristate acetate, which stimulates the hexose monophosphate shunt by a Ca2+ mediated mechanism, resulted in activation of phosphorylase without affecting cyclic AMP-dependent protein kinase or phosphorylase kinase activity, thus indicating a Ca2+-mediated activation of phosphorylase. This was, however, unaffected by EGTA. Prolonged incubation with phorbol myristate acetate was found to result in a parallel activation of phosphorylase and glycogen synthase secondary to a pronounced depletion of cellular glycogen. Addition of glucose to polymorphonuclear leukocytes resulted in total conversion of phosphorylase a to the b form and activation of glycogen synthase, however, when EGTA was included, the response to glucose was greatly amplified, thus indicating the synthase conversion is regulated by Ca2+ sensitive mechanisms which do not involve phosphorylase kinase. Addition of adrenalin to cells previously activated by glucose resulted in an increase in the concentration of cyclic AMP and activation of cyclic AMP-dependent protein kinase but deactivation of synthase was not effectuated under these conditions.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology*; D000242:Cyclic AMP / Q000097:blood / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D006003:Glycogen / Q000097:blood; D006006:Glycogen Synthase / Q000097:blood*; D006801:Humans; D009504:Neutrophils / Q000201:enzymology*; D010764:Phosphorylase Kinase / Q000097:blood; D010762:Phosphorylase a / Q000097:blood; D011494:Protein Kinases / Q000097:blood; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D006003:Glycogen; D000242:Cyclic AMP; D010762:Phosphorylase a; D006006:Glycogen Synthase; D011494:Protein Kinases; D010764:Phosphorylase Kinase; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium