Release of arachidonic acid from human platelets. A key role for the potentiation of platelet aggregability in normal subjects as well as in those with nephrotic syndrome.
Low (nonaggregating) concentrations of collagen that potentiate platelet aggregation did not induce the formation of measurable amount of malondialdehyde (MDA) but released small but significant amounts of radioactivity from 14C-arachidonic acid-labeled platelets. A major portion of the radioactive compounds released by nonaggregating concentrations of collagen existed as arachidonic acid and a minor part as thromboxane B2. The nephrotic syndrome enhances platelet aggregability, and this effect is abolished by correcting hypoalbuminemia in vitro and in vivo by the addition of albumin, which is the main carrier for free fatty acids, including arachidonic acid. Human albumin (fatty acid free) inhibited collagen-induced aggregation, MDA formation, and release of the radioactivity from 14C-arachidonic acid-labeled platelets in normals as well as in those with nephrotic syndrome. These data support our hypothesis that the main mechanism responsible for the potentiation of platelet aggregation is the release of arachidonic acid from platelet membrane phospholipids via the activation of phospholipase A2. Furthermore, enhanced platelet aggregation in the nephrotic syndrome was at least partly attributable to an increased availability of arachidonic acid released secondary to hypoalbuminemia. Albumin inhibits aggregation probably by binding to released arachidonic acid preventing arachidonic acid from being metabolized to potent aggregating substances, endoperoxides and thromboxane A2. The mechanism of release of arachidonic acid may play a key role in the potentiation of platelet aggregability in normals as well as in pathologic conditions such as the nephrotic syndrome.
D000418:Albumins / Q000494:pharmacology; D001095:Arachidonic Acids / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism*; D008315:Malondialdehyde / Q000378:metabolism; D009404:Nephrotic Syndrome / Q000097:blood / Q000503:physiopathology*; D010974:Platelet Aggregation
D000418:Albumins; D001095:Arachidonic Acids; D008315:Malondialdehyde