The modulation by serum albumin of rabbit platelet aggregation in response to exogenous sodium arachidonate.
This work presents a quantitative study of the modulation of platelet responsiveness to sodium arachidonate by serum albumin. Rabbit platelets suspended in protein-free buffer containing dextran aggregate reversibly in response to micromolar amounts of ADP and sodium arachidonate. The optimal concentration of arachidonate for aggregation response is 5 microM. Inhibition occurs at higher concentrations and is not related to thromboxane A2 formation since arachidonate inhibits ADP-induced aggregation of aspirin-treated platelets. Thin-layer chromatographic studies show that, at the high arachidonate levels sufficient to almost completely abolish platelet aggregation, the synthesis of thromboxane A2 persists. Albumin relieves the inhibition caused by excess arachidonate, whether the stimulus is arachidonate itself or ADP. This effect is due to arachidonate binding and is optimal at fatty acid/protein ratios near 4; no stimulation of platelets was observed at ratios less than 2. The optimal concentration of arachidonate for stimulation of platelet aggregation occurs in the range where albumin buffers the free arachidonate concentration most effectively, hence the extremely narrow range of total arachidonate concentrations effective for platelet response seen in the absence of albumin is enormously broadened in the presence of albumin. Albumin inhibits conversion of arachidonate to thromboxane A2 and hydroxy acids, especially at ratios of arachidonate/albumin below 10. Bilirubin (an albumin ligand) has no effect on albumin modulation of platelet response until the bilirubin/protein ratio exceeds 2. Palmitate progressively displaces arachidonate from albumin and affects the range of effective arachidonate concentrations but not the maximum response.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D011817:Rabbits; D012701:Serotonin / Q000097:blood; D012709:Serum Albumin / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000097:blood
D001095:Arachidonic Acids; D012709:Serum Albumin; D016718:Arachidonic Acid; D012701:Serotonin; D013928:Thromboxane A2