Thromboxane synthase inhibition causes re-direction of prostaglandin endoperoxides to prostaglandin D2 during collagen stimulated aggregation of human platelet rich plasma.
Prostanoid synthesis and release during collagen-induced aggregation of human platelet rich plasma (PRP) was studied using a novel gas chromatography/mass spectrometry assay technique. Aggregation was associated with the production of mainly thromboxane A2 (TXA2), measured as TXB2, and smaller amounts of the prostaglandins (PGs) D2, E2 and F2 alpha. UK 37,248 inhibited TXB2 formation by greater than 95% and increased the production of PGD2, PGE2 and PGF2 alpha twenty-fold. The relative amounts of these three prostanoids were not changed by UK 37,248. Even though high concentrations of PGD2 were formed, aggregation was not inhibited. In contrast, flurbiprofen inhibited aggregation, demonstrating that platelet aggregation produced by this concentration of collagen is cyclooxygenase dependent. These results support the proposal that the prostaglandin endoperoxides can induce aggregation alone, irrespective of the amount of PGD2 that is produced.
D001792:Blood Platelets / Q000378:metabolism*; D003094:Collagen / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D010974:Platelet Aggregation / Q000187:drug effects; D015230:Prostaglandin D2; D011449:Prostaglandin Endoperoxides / Q000097:blood*; D011457:Prostaglandins D / Q000097:blood* / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D016861:Cyclooxygenase Inhibitors; D007093:Imidazoles; D011449:Prostaglandin Endoperoxides; D011457:Prostaglandins D; D011458:Prostaglandins E; C029166:dazoxiben; D003094:Collagen; D013930:Thromboxane-A Synthase; D015232:Dinoprostone; D015230:Prostaglandin D2