THE DISTRIBUTION AND METABOLISM OF ARACHIDONIC ACID IN RABBIT PLATELETS DURING AGGREGATION AND ITS MODIFICATION BY DRUGS

Abstract

1Gas chromatographic and radio‐isotope labelling techniques have been used to establish the origin of the arachidonic acid used by the platelet cyclo‐oxygenase for the synthesis of pro‐aggregatory prostaglandin endoperoxide derivatives. 2Measurements of total platelet arachidonate content indicated that more than 95% is esterified in the phosphatide fraction of the cells. 3During 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. 4The phosphatidylethanolamine, phosphatidylcholine and phosphatidylinositol fractions are major sources of the arachidonate thus used. 5Indomethacin, 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. 6Mepacrine, 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. 7It is suggested that phospholipase A2 plays a key role in the initial events during platelet aggregation induced by collagen. 1977 British Pharmacological Society