title: Monocyclic peroxides as inhibitors of arachidonic acid and prostaglandin endoperoxide analog initiated aggregation of human platelets.
abstract: Arachidonic acid initiates the irreveresible aggregation of human platelets on conversion to the bicyclic prostaglandin endoperoxides, PGG2 and PGH2. An enzyme in arterial walls catalyzes the conversion of PGG2 and PGH2 to PGX, which inhibits human platelet aggregation. Preincubation with monocyclic peroxides (3-(alpha-hydroxyethyl)-1,2-dioxane, 3-(alpha-hydroxypropyl)-1,2-dioxolane or 3-methyl-3-(hydroxymethyl)-1,2-dioxolane) completely inhibited arachidonic acid initiated aggregation. Similarly, two analogs of PGH2, (15S)-hydroxy-9 alpha, 11 alpha-(epoxymethano)prosta-5Z, 13E-dienoic and (15S)-hydroxy-11 alpha, 9 alpha-(epoxymethano)prosta-5Z, 13E-dienoic acids, initiated irreversible aggregation of platelets. but were completely blocked by the monocyclic peroxides. Aggregation initiated by ADP or epinephrine was also completely inhibited by the cyclic peroxides. Aggregation of human platelets appears initiated through an endoperoxide receptor which can combine with either the natural bicyclic prostaglandin peroxides or the synthetic monocyclic peroxides. Natural inhibitors, such as PGX, may well be monocyclic endoperoxides similar to the compounds studied here.
mesh_terms: D001095:Arachidonic Acids / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D010545:Peroxides / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*
chemical_list: D001095:Arachidonic Acids; D010545:Peroxides