Platelet activating factor (PAF) causes human platelet aggregation through the mechanism of membrane modulation.
Recent investigations have shown that human and canine platelets possess a new pathway for securing irreversible platelet aggregation independent of ADP secretion and prostaglandin synthesis. Platelet activating factor (PAF) is a potent aggregating agent for rabbit platelets and is also reputed to stimulate the cells by a completely independent pathway. Since the newly recognized mechanism in human and dog cells, termed membrane modulation, might be mediated by PAF, we evaluated the influence of this agent on human cells. Results of that study demonstrated that PAF did not activate platelets through an independent pathway and was not involved in the mechanism of membrane modulation. In the present investigation we have examined the possibility that PAF might act on human platelets through the mechanism of membrane modulation. Human platelets were made refractory to amounts of PAF routinely causing irreversible aggregation by prolonged incubation of C-PRP at 37 degrees C, by exposure to PGI2 or aspirin, or by aggregation-disaggregation of control or aspirin treated cells. Epinephrine at concentrations which did not cause aggregation turned on the mechanism of membrane modulation in refractory platelets and restored their sensitivity to PAF. Thus, PAF does not appear to activate human platelets through a unique, independent pathway. Rather, it usually causes irreversible aggregation of human cells through the mechanisms of ADP secretion and thromboxane synthesis or, as shown in this study, can be dependent on membrane modulation.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology; D006801:Humans; D010972:Platelet Activating Factor / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects*; D013929:Thromboxane B2 / Q000097:blood; D013997:Time Factors
D001095:Arachidonic Acids; D010972:Platelet Activating Factor; D016718:Arachidonic Acid; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; D011464:Epoprostenol; D001241:Aspirin; D004837:Epinephrine