Platelet and Blood Vessel Arachidonate Metabolism and Interactions

Abstract

A B S T R A C T Exogenous arachidonate addition to intact platelets, in the absence or the presence of blood vessel microsomes, results in the production of thromboxane B2 (the stable degradation product of thromboxane A2) 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,a (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 ['4C]arachidonate-labeled phospholipids, adhered to the blood vessel segments and released some thromboxane B2. The subsequent addition of thrombin facilitated the release of endogenous arachidonate and thromboxane, but no labeled 6-keto-PGF,, 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.

Synthesis of Prostacyclin from Platelet-derived Endoperoxides by Cultured Human Endothelial Cells

“…A similar effect was noted when thrombin was the stimulus. Monolayer experiments carried out in the presence of the thromboxane synthetase inhibitors imidazole and U54701 resulted in an increase in PGI2 production as reported by others (14)(15)(16). In the case of ionophore stimulation, counts in the 6-keto-PGF1,, TLC peak increased from 491 to 3,826 epm with imidazole, and to 4,177 cpm with U54701.…”

“…Although endothelial cells can synthesize PGI2 from endogenous precursors (17)(18)(19) or from exogenously provided endoperoxides (6) or arachidonate (1,6,16), PGI2 synthesis by endothelial cells from platelet-derived endoperoxides has been demonstrated only in the presence of thromboxane synthetase inhibitors (14)(15)(16). These results indicated to us that utilization of platelet endoperoxides for PGI2 synthesis by ASAtreated endothelial cells might be possible even in the absence of thromboxane synthetase inhibitors.…”

Metabolism and functional effects of plant-derived omega-3 fatty acids in humans

“…This may result in modulation of platelet aggregation, as this is partly regulated by AA and EPA-derived eicosanoids [255,256]. Consuming 18 g/d ALA for 23 days decreased collagen-induced platelet aggregation in healthy men compared to those consuming an LA-rich diet [150].…”

In vivo platelet aggregation in the rat: dependence on extracellular divalent cation and inhibition by nonsteroidal anti‐inflammatory drugs

“…Both PGI2 and TXA2 are produced from the prostaglandin endoperoxide PGH2. The hypothesis that blood vessels use platelet PGH2 for PGI2 synthesis is disputed by Needleman, Wyche & Raz (1979). Therefore unlike in vitro platelet aggregation studies using collagen, where the aggregation occurs as a direct result of platelet activiation, the in vivo effect of collagen-induced platelet aggregation may be due to several interactions occurring within the vascular system.…”