The distribution and metabolism of arachidonic acid in rabbit platelets during aggregation and its modification by drugs.
1 Gas chromatographic and radio-isotope labelling techniques have been used to establish the origin of the arachindonic acid used by the platelet cyclo-oxygenase for the synthesis of pro-aggregatory prostaglandin endoperoxide derivatives. 2 Measurements of total platelet arachidonate content indicated that more than 95% is esterified in the phosphatide fraction of the cells. 3 During aggregation by collagen or thrombin as much as 80% of the total platelet arachidonate may be liberated and transformed by the platelet enzymes into hydroxyacids and other more polar compounds. 4 The phosphatidylethanolamine, phosphatidylcholine and phosphatidylinositol fractions are major sources of the arachidonate thus used. 5 Indomethacin, which prevents platelet aggregation by inhibiting the cyclo-oxygenase, did not affect this release of arachidonate from the phosphatides but did prevent the transformation of arachidonate to endoperoxide derivatives. 6 Mepacrine, a drug which possesses weak anti-phospholipase activity in platelets, also prevents aggregation by collagen or thrombin, but seems to do so by preventing substrate release from the phosphatide fraction. 7 It is suggested that phospholipase A2 plays a key role in the initial events during platelet aggregation induced by collagen.
D000818:Animals; D001095:Arachidonic Acids / Q000097:blood*; D001792:Blood Platelets / Q000032:analysis / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D002250:Carbon Radioisotopes; D055598:Chemical Phenomena; D002621:Chemistry; D002849:Chromatography, Gas; D003094:Collagen / Q000494:pharmacology; D005227:Fatty Acids / Q000097:blood; D006868:Hydrolysis; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008055:Lipids / Q000097:blood; D008297:Male; D010713:Phosphatidylcholines / Q000378:metabolism; D010740:Phospholipases / Q000097:blood; D010743:Phospholipids / Q000097:blood; D010758:Phosphorus / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects*; D011796:Quinacrine / Q000494:pharmacology; D011817:Rabbits; D013917:Thrombin / Q000494:pharmacology
D001095:Arachidonic Acids; D002250:Carbon Radioisotopes; D005227:Fatty Acids; D008055:Lipids; D010713:Phosphatidylcholines; D010743:Phospholipids; D010758:Phosphorus; D003094:Collagen; D010740:Phospholipases; D013917:Thrombin; D011796:Quinacrine; D007213:Indomethacin