title: Control of platelet glycogenolysis; Activation of phosphorylase kinase by calcium.
abstract: An apparent enigma during platelet aggregation is that increased glycogenolysis occurs despite a fall in cyclic AMP levels; Activation by a classical cascade is therefore unlikely, and an alternative stimulus for phosphorylase a formation was sought. It was found that low levels of Ca-2+ markedly activate phosphorylase b kinase from human platelets, with a Ka of 0i muM Ca-2+, which is similar to that for the skeletal muscle enzyme; The kinase activity is unstable, and on enzyme ageing is a 50% loss in activity with the Ka decreasing to 0.33 muM Ca-2+. In unstilulated platelets, phosphorylase a was 13.3% of toal measured activity, and glycogen synthetase I was 32.3%. Aggregation induced by ADP did not change the percentage of I synthetase, while increasing that for phosphorylase a. Dibutyryl cyclic AMP did, as expected, increase the percentage of both phosphorylated enzymes; These findings suggest that the natural activator of platelet glycogenolysis during aggregation is Ca-2+, which directly stimulates phosphorylase b kinase without altering glycogen synthetase activity. The cyclic AMP-dependent protein kinase does not appear to be involved;
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000249:Adenosine Monophosphate / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology*; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D006003:Glycogen / Q000097:blood*; D006006:Glycogen Synthase / Q000097:blood; D006801:Humans; D007700:Kinetics; D010764:Phosphorylase Kinase / Q000097:blood*; D006005:Phosphorylases / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects
chemical_list: D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D003994:Bucladesine; D006003:Glycogen; D006005:Phosphorylases; D006006:Glycogen Synthase; D010764:Phosphorylase Kinase; D002118:Calcium