Platelet dysfunction in uremia. II. Correction by arachidonic acid of the impaired exposure of fibrinogen receptors by adenosine diphosphate or collagen.
Previous studies showed that platelets from patients with uremia have a marked decrease in their aggregation response to adenosine diphosphate (ADP) and collagen as single agents or as a pair. It is known that small amounts of arachidonic acid can enhance the sensitivity of platelets to concentrations of ADP or collagen that do not cause aggregation when used singly. Stimulation of platelets by certain agonists induces the formation of fibrinogen receptors on the platelet surface. The binding of fibrinogen that follows is essential for platelet aggregation. The platelet membrane glycoprotein IIb-IIIa complex appears to be the site of the fibrinogen receptor. Therefore, we investigated the binding of iodine 125-labeled fibrinogen to uremic platelets exposed to ADP, collagen, or arachidonic acid as single agents and as pairs. When aggregation and binding were studied in response to ADP, collagen, or the combination of ADP with collagen, uremic platelets had reduced aggregation and bound abnormally low amounts of fibrinogen. In contrast, platelets from patients with uremia bound as much 125I-fibrinogen and aggregated as well as controls when ADP or collagen were used in combination with low concentrations of arachidonic acid. Studies with a monoclonal antibody (B 79.7) suggested that the number of glycoprotein IIb-IIa molecules is the same in uremic and normal platelets. We conclude that uremia impairs the exposure of fibrinogen receptors on platelets in response to ADP or collagen without affecting the glycoprotein IIb-IIa complex quantitatively. Correction by arachidonic acid of the impaired aggregation and exposure of fibrinogen receptors by ADP or collagen suggests that abnormal release of endogenous arachidonic acid plays a role in the dysfunction of platelets in uremia.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D001667:Binding, Competitive; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D003094:Collagen / Q000494:pharmacology; D005260:Female; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014511:Uremia / Q000097:blood*
D001095:Arachidonic Acids; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D005340:Fibrinogen; D003094:Collagen