Inositol 1,4,5-trisphosphate induces aggregation and release of 5-hydroxytryptamine from saponin-permeabilized human platelets.
Inositol 1,4,5-trisphosphate induces aggregation and the release of [3H]5-hydroxytryptamine from human platelets rendered permeable with saponin. This action of inositol 1,4,5-trisphosphate is associated with a significant formation of thromboxane B2, activation of phospholipase C, and phosphorylation of 20,000- and 40,000-dalton proteins, which are the substrates for myosin light chain kinase and protein kinase C, respectively. All of these responses are blocked by the cyclooxygenase inhibitors indomethacin and aspirin and the dual cyclooxygenase and lipoxygenase inhibitor 3-amino-1-[m-(trifluoromethyl)phenyl]-2-pyrazoline (BW 755C). These data indicate that platelet activation by inositol 1,4,5-trisphosphate is initiated by the mobilization of Ca2+, which leads to phospholipase A2 activation. The thromboxanes and endoperoxides that are subsequently generated then induce activation via cell surface receptors.
Watson
S P
SP
Ruggiero
M
M
Abrahams
S L
SL
Lapetina
E G
EG
D000255:Adenosine Triphosphate / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects*; D002463:Cell Membrane Permeability / Q000187:drug effects; D003593:Cytoplasm / Q000378:metabolism; D004075:Diglycerides / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000494:pharmacology*; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology; D010712:Phosphatidic Acids / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism*; D013403:Sugar Phosphates / Q000494:pharmacology*
D004075:Diglycerides; D007295:Inositol Phosphates; D010703:Phorbol Esters; D010712:Phosphatidic Acids; D012503:Saponins; D013403:Sugar Phosphates; C044297:1,2-didecanoylglycerol; D012701:Serotonin; D015240:Phorbol 12,13-Dibutyrate; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin