Platelet and blood vessel arachidonate metabolism and interactions.
Exogenous arachidonate addition to intact platelets, in the absence or the presence of blood vessel microsomes, results in the production of thromboxane B(2) (the stable degradation product of thromboxane A(2)) only. Prostaglandin (PG) endoperoxides are released from intact platelets only when thromboxane synthetase is inhibited. Thus, addition of exogenous arachidonate to imidazole-pretreated platelets in the presence of bovine aorta microsomes (source of prostacyclin synthetase) results predominantly in the synthesis of 6-keto-PGF(1alpha) (the stable degradation product of prostacyclin). Strips of intact aorta were removed from aspirin-treated rabbits, thus the isolated blood vessels were unable to convert endogenous or exogenous arachidonate to prostacyclin. Human platelets, with [(14)C]arachidonate-labeled phospholipids, adhered to the blood vessel segments and released some thromboxane B(2). The subsequent addition of thrombin facilitated the release of endogenous arachidonate and thromboxane, but no labeled 6-keto-PGF(1alpha) was detectable. There is therefore no direct chemical evidence of PG-endoperoxide release from human platelets during either aggregation or adhesion, which therefore precludes the possibility that blood vessels use platelet PG-endoperoxide for prostacyclin synthesis. Imidazole inhibited the thromboxane synthetase in the labeled platelets, and thereafter thrombin stimulation resulted in the release of platelet-derived, labeled PG-endoperoxides that were converted to labeled prostacyclin by the vascular prostacyclin synthetase. The latter result suggests a potential antithrombotic therapeutic benefit might be achieved using an effective thromboxane synthetase inhibitor.
D000818:Animals; D001095:Arachidonic Acids / Q000097:blood / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism*; D001808:Blood Vessels / Q000378:metabolism*; D002417:Cattle; D011464:Epoprostenol / Q000096:biosynthesis / Q000097:blood; D006801:Humans; D066298:In Vitro Techniques; D008861:Microsomes / Q000378:metabolism; D011463:Prostaglandins H / Q000097:blood / Q000378:metabolism; D011817:Rabbits; D013929:Thromboxane B2 / Q000096:biosynthesis / Q000097:blood
D001095:Arachidonic Acids; D011463:Prostaglandins H; D013929:Thromboxane B2; D011464:Epoprostenol