A role for prostaglandins and thromboxanes in the exposure of platelet fibrinogen receptors.
Exposure of fibrinogen receptors by a variety of agonists is a prerequisite for platelet aggregation. Because the synthesis of prostaglandins and thromboxane A2 also occurs during platelet aggregation we wondered whether these agents participate in the exposure of platelet fibrinogen receptors. Therefore, we measured the binding of human 125I-fibrinogen to gel-filtered normal human platelets after prostaglandin and thromboxane synthesis had been inhibited by aspirin or indomethacin. The fibrinogen binding assay was performed at 37 degrees C but without stirring to prevent the formation of platelet aggregates. Platelet secretion, measured with [14C]serotonin, did not occur during the procedure. Aspirin or indomethacin inhibited fibrinogen binding stimulated by 10 microM epinephrine by 53%, and inhibited fibrinogen binding stimulated by 1-2 microM ADP by 37.1%. However, ADP at concentrations greater than 2 microM returned fibrinogen binding toward control values. Scatchard analysis demonstrated that aspirin decreased the number but not the affinity of the exposed fibrinogen receptors. To determine whether prostaglandins are capable of directly exposing fibrinogen receptors, prostaglandin H2 was used to stimulate platelets in the fibrinogen binding assay. Prostaglandin H2 exposed approximately 54,000 fibrinogen receptors/platelet and corrected the deficit in receptor exposure induced by aspirin. These studies demonstrate that platelet prostaglandins or thromboxane A2 can play a direct role in the exposure of platelet fibrinogen receptors. In addition, they suggest that the synthesis of prostaglandins and thromboxane A2 by stimulated platelets may be all that is required for optimal secondary platelet aggregation.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects*; D004837:Epinephrine / Q000494:pharmacology; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D010980:Platelet Membrane Glycoproteins; D011453:Prostaglandins / Q000494:pharmacology*; D011454:Prostaglandins A / Q000494:pharmacology; D011463:Prostaglandins H / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000187:drug effects*; D013931:Thromboxanes / Q000494:pharmacology*
D010980:Platelet Membrane Glycoproteins; D011453:Prostaglandins; D011454:Prostaglandins A; D011463:Prostaglandins H; D011956:Receptors, Cell Surface; D013931:Thromboxanes; D000244:Adenosine Diphosphate; D005340:Fibrinogen; D001241:Aspirin; D007213:Indomethacin; D004837:Epinephrine