Platelet-activating factor is a weak platelet agonist: evidence from normal human platelets and platelets with congenital secretion defects.
We have examined the effects of a novel platelet agonist, platelet activating factor (PAF), on human platelets. Irreversible aggregation and 14C-serotonin secretion in response to PAF (10(-5) M) was found to be dependent on both thromboxane production and secreted adenosine diphosphate (ADP). Liberation of arachidonic acid (AA) from membrane-bound phospholipids is a prerequisite step in platelet thromboxane production. Studies with 3H-AA-labeled platelets revealed that PAF (10(-5) M) was a weak stimulus for the mobilization of AA. In addition, PAF (10(-5) M) was found to be a weak inducer of thromboxane synthesis (mean = 6 pmol/10(8) platelets) as compared to thrombin 5 U/ml (mean = 177 pmol/10(8) platelets), measured using a radioimmunoassay for thromboxane B2. Formation of phosphatidic acid is an early step in stimulus-response coupling in platelets. Our studies indicate that PAF is a weak stimulus for phosphatidic acid formation as well. To obtain further insights into its action, we examined the effect of PAF on platelets from three groups of patients with congenital secretion defects: patients with the storage pool deficiency, those with impaired thromboxane synthesis due to impaired liberation of AA from phospholipids, and those with impaired secretion despite normal granule stores and thromboxane production. The response to PAF was impaired in all patients, providing further evidence that PAF-induced platelet activation is dependent on secreted ADP and thromboxane A2 synthesis, and occurs by mechanisms common to a number of agonists. Overall, these studies indicate that PAF is a weak platelet agonist.
D000241:Adenosine / Q000031:analogs & derivatives; D000255:Adenosine Triphosphate / Q000494:pharmacology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001791:Blood Platelet Disorders / Q000151:congenital*; D006801:Humans; D010972:Platelet Activating Factor / Q000502:physiology*; D010974:Platelet Aggregation; D012701:Serotonin / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology; D013931:Thromboxanes / Q000096:biosynthesis
D001095:Arachidonic Acids; D010972:Platelet Activating Factor; D013931:Thromboxanes; D016718:Arachidonic Acid; D012701:Serotonin; C010959:5'-(4-fluorosulfonylbenzoyl)adenosine; D000255:Adenosine Triphosphate; D013917:Thrombin; D000241:Adenosine