Prostaglandin endoperoxides. A new concept concerning the mode of action and release of prostaglandins.
Methods were developed for quantitative determination of the three major metabolites of arachidonic acid in human platelets, i.e., 12L-hydroxy-5,8,10,14-eicosatetraenoic acid (HETE), 12L-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and 8-(1-hydroxy-3-oxopropyl)-9,12L-dihydroxy-5,10-heptadecadienoic acid (PHD). Aggregation of washed platelets by thrombin was accompanied by release of 1163-2175 ng/ml of HETE, 1129-2430 ng/ml of HHT, and 998-2299 ng/ml of PHD. The amount of PGG(2) (prostaglandin G(2)) produced as calculated from the sum of the amounts of its metabolites (HHT and PHD) was 2477-5480 ng/ml. In contrast, the amounts of PGE(2) (prostaglandin E(2)) and PGF(2alpha) (prostaglandin F(2alpha)) released were approximately two orders of magnitude lower. In this system, the prostaglandins thus exert their biological action through the endoperoxides, which are almost exclusively metabolized to nonprostanoate structures and only to a small extent to the classical prostaglandins. Platelets from subjects given aspirin produced less than 5% of the above mentioned amounts of HHT and PHD, whereas the production of HETE was stimulated about 3-fold. This provides additional evidence for our earlier proposal [Hamberg, M., Svensson, J., Wakabayashi, T. & Samuelsson, B. (1974) Proc. Nat. Acad. Sci. USA 71, 345-349] that the anti-aggregating effect of aspirin is through inhibition of PGG(2) formation.
D001095:Arachidonic Acids / Q000031:analogs & derivatives / Q000378:metabolism*; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000097:blood; D005233:Fatty Alcohols / Q000097:blood; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D010545:Peroxides / Q000097:blood*; D010974:Platelet Aggregation; D011453:Prostaglandins / Q000096:biosynthesis*; D013917:Thrombin
D001095:Arachidonic Acids; D005231:Fatty Acids, Unsaturated; D005233:Fatty Alcohols; D010545:Peroxides; D011453:Prostaglandins; D013917:Thrombin; D001241:Aspirin; D007213:Indomethacin