Low concentrations of sodium azide specifically inhibit a thromboxane A2 pathway in human platelets.
Sodium azide completely inhibits the serotonin release induced by ADP, arachidonic acid and the thromboxane A2 mimetic U46619, but does not have any effect on the activation by PMA. Collagen and thrombin are inhibited when used at low concentrations, but not at high concentration. This pattern of activation suggests that the inhibition by azide is not a metabolic inhibition. The antagonism of U46619-induced secretion was further studied and was shown to be non-competitive. It is selective for certain components of the U46619 stimulus-response coupling: aggregation, serotonin secretion and the activation of protein kinase C are completely or almost completely inhibited by 300 microM sodium azide. Shape change, calcium elevation, cytoplasmic alkalinization and phosphorylation of myosin light chain are only partially modified. This suggests that azide may specifically inhibit one of the different forms of thromboxane A2 receptors present in platelets.
Rubinstein
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Department of Medical Biology, University of Tennessee Medical Center, Knoxville 37920.
Urso
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Carroll
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D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001081:Apyrase / Q000494:pharmacology; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001386:Azides / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D003094:Collagen / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects; D011450:Prostaglandin Endoperoxides, Synthetic / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D012636:Secretory Rate / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism*; D019810:Sodium Azide; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors*
D001386:Azides; D011450:Prostaglandin Endoperoxides, Synthetic; D016718:Arachidonic Acid; D012701:Serotonin; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D003094:Collagen; D019810:Sodium Azide; D011493:Protein Kinase C; D009219:Myosin-Light-Chain Kinase; D013917:Thrombin; D001081:Apyrase; D013755:Tetradecanoylphorbol Acetate; D001241:Aspirin; D002118:Calcium