Abstract

Platelet production of 12L-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and 8-(1-hydroxy-3-oxopropyl)-9, 12L-dihydroxy-5,10-heptadecadienoic acid (PHD), two metabolites of the prostaglandin cyclic endoperoxides PGG2 and PGH2, was found in this investigation to occur primarily in a platelet microsomal fraction consisting almost exclusively of membranes. To further localize the membrane site of platelet prostaglandin biosynthesis, the present study has used a cytochemical technique employing 3,3'-diaminobenzidine as an oxidizable substrate. The reaction product was found to localize in the platelet dense tubular system. Formation of the reaction product was inhibited by aminotriazole. In similar concentrations, aminotriazole inhibited collagen and arachidonic acid aggregation, the second wave of ADP and epinephrine aggregation, but failed to inhibit aggregation by PGG2 and A23187. A study of the mechanism of action of aminotriazole revealed inhibition of formation of HHT and PHD. The results localize platelet prostaglandin biosynthesis to the membranes of the dense tubular system.