Prostaglandin biosynthesis in platelets: demonstration and role of prostaglandin H2 leads to E2 isomerase.
Double-labeled [3H/14C]-prostaglandin endoperoxide H2 was used to assess the presence in platelets of enzymatic activity for conversion of the endoperoxides to prostaglandin E2. This enzymatic activity (prostaglandin H2 leads to E2 isomerase) involves the selective removal of a hydrogen from the C-9 carbon atom of the endoperoxide molecule and is subject to an isotope discriminatory effect against tritium-labeled molecules. Rabbit washed platelet suspension was pre-incubated for 1 min, with imidazole (1 mM) to inhibit thromboxane A2 generation and [3H/14C]--prostaglandin H2 was added. Analysis of the [3H] and [14C] radioactive products in incubations with native vs. heat denatured platelets indicated that native platelets convert the endoperoxide enzymatically to mainly prostaglandin E2. Thus, although arachidonic acid released endogenously or added exogenously to platelets is converted mainly to thromboxane B2 and 120H-17:3 acid, platelets appear to possess prostaglandin H2 leads to E2 isomerase activity which becomes manifested when thromboxane synthetase activity is inhibited.
D000818:Animals; D001095:Arachidonic Acids / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007535:Isomerases / Q000378:metabolism*; D011449:Prostaglandin Endoperoxides / Q000097:blood*; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E; D011463:Prostaglandins H / Q000097:blood*; D011817:Rabbits; D013929:Thromboxane B2 / Q000097:blood
D001095:Arachidonic Acids; D007093:Imidazoles; D011449:Prostaglandin Endoperoxides; D011453:Prostaglandins; D011458:Prostaglandins E; D011463:Prostaglandins H; D013929:Thromboxane B2; D007535:Isomerases