LOCALIZATION OF PLATELET PROSTAGLANDIN PRODUCTION IN PLATELET DENSE TUBULAR SYSTEM

  • 1 January 1976
    • journal article
    • research article
    • Vol. 83  (2) , 283-298
Abstract
Platelet [human] production of 12L-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and 8-(1-hydroxy-3-oxopropyl)-9, 12L-dihydroxy-5,10-heptadecadienoic acid (PHD), 2 metabolites of the prostaglandin [PG] cyclic endoperoxides PGG2 and PGH2, occurred primarily in a platelet microsomal fraction consisting almost exclusively of membranes. To further localize the membrane site of platelet prostaglandin biosynthesis, a cytochemical technique employing 3,3''-diaminobenzidine as an oxidizable substrate was used. The reaction product was localized 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 2nd wave of ADP and epinephrine aggregation, but failed to inhibit aggregation by PGG2 and A23187 [2-[(3.beta., 9.alpha., 11.beta.-trimethyl)-8-(2-pyrrolecarboxymethyl)-,1,7-dioxaspiro[6.6] undecyl-2.beta.-methyl]-5-methylami nobenzoxazole-4-carboxylic acid]. A study of the mechanism of action of aminotriazole revealed inhibition of formation of HHT and PHD. The results localized platelet prostaglandin biosynthesis to the membranes of the dense tubular system.