Aggregation and inhibition of rat platelets, and the formation of endoperoxide metabolites.
In citrated rat platelets, arachidonic acid (AA) at 1 mM could not induce aggregation unlike human or rabbit platelets. However, preincubation of platelet rich plasma (PRP) prepared in sodium citrate with AA (1 mM) enhanced the aggregation induced by collagen suspension or adenosine diphosphate (ADP), and this enhancement was abolished by the preincubation of PRP with indomethacin. Arachidonic acid at a higher concentration (6 mM) induced aggregation; but it was not attenuated by preincubation of indomethacin indicating that this aggregation may not be augmented by prostaglandins (PGs) or their intermediates. The major product of endoperoxide metabolites formed during collagen-induced aggregation was thromboxane A2 (TXA2) as measured in terms of TXB2, the stable metabolite. Preincubation of citrated PRP with imidazole neither abolished the enhancement of ADP-induced or collagen-induced aggregation by AA (1mM), nor attenuated the aggregation induced by ADP or collagen alone; but imidazole inhibited the synthesis of TXB2 by more than 90%. In heparinized platelets, arachidonic acid at 0.25 mM induced the aggregation, and this was inhibited by preincubation of the PRP with indomethacin. Heparinized PRP was much more sensitive to aggregating agents than citrated PRP. This implied that aggregation of rat platelets is more dependent on calcium than human o rabbit platelets. Preincubation of heparinized PRP with imidazole inhibited AA-induced aggregation, and the inhibition was abolished by the preincubation of vitamin E. This result implied that inhibition of AA-induced aggregation by imidazole is due to products of platelet lipoxygenase rather than due to the inhibition of TXA2 synthesis.
D000818:Animals; D006493:Heparin / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D011449:Prostaglandin Endoperoxides / Q000096:biosynthesis*; D011453:Prostaglandins / Q000378:metabolism; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D013928:Thromboxane A2 / Q000096:biosynthesis; D013929:Thromboxane B2 / Q000037:antagonists & inhibitors; D014810:Vitamin E / Q000378:metabolism
D011449:Prostaglandin Endoperoxides; D011453:Prostaglandins; D014810:Vitamin E; D013929:Thromboxane B2; D013928:Thromboxane A2; D006493:Heparin; D011796:Quinacrine; D007213:Indomethacin