Shape change induced in human platelets by platelet-activating factor. Correlation with the formation of phosphatidic acid and phosphorylation of a 40,000-dalton protein.
Washed human platelets that have been separated from plasma in the presence of prostacyclin are activated by the addition of platelet activating factor (PAF). Activation (shape change, serotonin release, and aggregation) correlates closely with the formation of phosphatidic acid and the phosphorylation of a 40,000-dalton protein. Platelet shape change, formation of phosphatidic acid, and protein phosphorylation precede aggregation and are induced at lower concentrations of PAF than those required to induce release of serotonin and platelet aggregation. Platelet shape change, formation of phosphatidic acid, and protein phosphorylation induced by PAF are not affected by trifluoperazine or indomethacin. This indicates that these responses are independent of the liberation of arachidonic acid from platelet phospholipids and the metabolism of arachidonic acid via cyclooxygenase and lipoxygenase. These responses are, however, inhibited by prostacyclin. Platelet shape change is the first measurable physiologic response to platelet agonists and may be associated with the stimulation of phospholipase C, inducing formation of 1,2-diacylglycerol and its phosphorylated product, phosphatidic acid. Transient formation of 1,2-diacylglycerol may also induce the specific activation of the protein kinase C that phosphorylates a 40,000-dalton protein.
D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D001798:Blood Proteins / Q000302:isolation & purification / Q000378:metabolism*; D011464:Epoprostenol / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008855:Microscopy, Electron, Scanning; D008970:Molecular Weight; D010712:Phosphatidic Acids / Q000097:blood*; D010766:Phosphorylation; D010972:Platelet Activating Factor / Q000502:physiology*; D014268:Trifluoperazine / Q000494:pharmacology
D001798:Blood Proteins; D010712:Phosphatidic Acids; D010972:Platelet Activating Factor; D014268:Trifluoperazine; D011464:Epoprostenol; D007213:Indomethacin