Thrombin and C-kinase activators potentiate calcium-stimulated arachidonic acid release in human platelets.
Human platelets were depleted of intracellular Ca2+ and then made selectively permeable to external Ca2+ by addition of the ionophore ionomycin. In this cell system a rapid release of arachidonic acid was seen in direct response to added Ca2+ at concentrations corresponding to cytosolic Ca2+ levels measured in thrombin-stimulated platelets. Thrombin and other activators of Ca2+/phospholipid-dependent protein kinase (C-kinase) potentiated the Ca2+-stimulated arachidonic acid release while exerting little or no effect in the absence of added Ca2+. Agents which increase (R59022) or decrease (isoquinolinesulphonylmethylpiperazine) the activation of C-kinase correspondingly enhanced or inhibited, respectively, the potentiation of arachidonic acid release caused by thrombin. These results support the hypothesis that arachidonic acid release in human platelets is regulated by a co-operative action between intracellular Ca2+ and C-kinase.
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology*; D004075:Diglycerides / Q000494:pharmacology; D004224:Diterpenes; D004357:Drug Synergism; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D010743:Phospholipids / Q000097:blood; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011744:Pyrimidinones / Q000494:pharmacology; D013729:Terpenes / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology*
D001095:Arachidonic Acids; D004075:Diglycerides; D004224:Diterpenes; D007546:Isoquinolines; D010743:Phospholipids; D010879:Piperazines; D011744:Pyrimidinones; D013729:Terpenes; D013844:Thiazoles; D016718:Arachidonic Acid; C011309:mezerein; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C038237:1-oleoyl-2-acetylglycerol; C047505:R 59022; D011493:Protein Kinase C; D013917:Thrombin; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium