[Synthesis of thromboxane A2: limiting stages of primary thrombocyte aggregation in humans initiated by arachidonic acid and its metabolic products]

A photocolorimetric method has been employed for kinetic investigation of aggregation of human platelets under the effects of arachidonic acid (AA) and the products of its metabolism in the platelets. The platelet aggregation was induced by AA and prostaglandin (PG)H2, the precursors of thromboxane (Tx). The initial rate of aggregation depended on AA and PGH2, concentrations. The nature of the influence of selective inhibitors of PGH-synthetase (indomethacin) and PGH-convertase (imidazole) on the rate of aggregation is suggestive of the rate-limiting type of enzymatic reactions of AA conversion into TxA2. Addition to the platelet suspension of solubilized PGH-convertase accelerates the PGH2-induced aggregation. Analysis of platelet aggregation processes induced by AA and PGH2 demonstrated that the enzymatic synthesis of TxA2 is one of the rate-limiting steps within the framework of molecular modifications responsible for the platelet aggregate formation.