Differential effects of spermine on aggregation, inositol phosphate formation and protein phosphorylation in human platelets in response to thrombin, arachidonic acid and lysophosphatidic acid.
Platelet aggregation stimulated by thrombin, arachidonic acid or lysophosphatidic acid is associated with rapid phosphorylation of two platelet proteins, myosin light chain and a 47 kDa protein. The polyamine, spermine, inhibited platelet aggregation stimulated by all three agents. Spermine inhibited thrombin-stimulated phosphorylation of myosin light chain and the 47 kDa proteins as well as thrombin-induced production of the inositol phosphates and phosphatidic acid. In contrast, spermine did not inhibit phosphorylation of either protein or the formation of inositol phosphates and phosphatidic acid in response to arachidonic acid or lysophosphatidic acid. Although spermine has been demonstrated to inhibit both phosphatidylinositol-specific phospholipase C and calcium-dependent protein kinases in cell free systems, these results suggest that, in the intact platelet, spermine does not directly inhibit these enzymes. Inhibition of aggregation stimulated by arachidonic acid and lysophosphatidic acid is secondary to interference with platelet-platelet interaction but not with platelet activation. In contrast, spermine inhibits thrombin-induced platelet activation. This thrombin-specific inhibition may be related to interference with the binding of thrombin to its receptor or to its catalytic substrate on the cell surface.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D006801:Humans; D007295:Inositol Phosphates / Q000096:biosynthesis*; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008970:Molecular Weight; D009218:Myosins / Q000378:metabolism; D010712:Phosphatidic Acids / Q000378:metabolism; D010766:Phosphorylation; D010974:Platelet Aggregation / Q000187:drug effects*; D011494:Protein Kinases / Q000378:metabolism; D013096:Spermine / Q000494:pharmacology*; D013403:Sugar Phosphates / Q000096:biosynthesis*; D013917:Thrombin / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000378:metabolism
D001095:Arachidonic Acids; D007295:Inositol Phosphates; D008244:Lysophosphatidylcholines; D010712:Phosphatidic Acids; D013403:Sugar Phosphates; D016718:Arachidonic Acid; D013096:Spermine; D011494:Protein Kinases; D010738:Type C Phospholipases; D013917:Thrombin; D009218:Myosins; D002118:Calcium