Inhibitory effects of tryptophan pyrolysis products on human platelet aggregation through inhibition of prostaglandin endoperoxide synthetase

To determine the effects of the carcinogenic heterocyclic amines on the stimulus-reaction system in cells, the effects of several such amines, including 3-amino-1,4-dimethyl-5H-pyridol[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), on human platelet aggregation and of Trp-P-1 and Trp-P-2 on human polymorphonuclear leucocyte aggregation were investigated. Of the carcinogens studied, only Trp-P-1 and Trp-P-2 had potent inhibitory effects on human platelet aggregation induced by sodium arachidonate. The concentrations of Trp-P-1 and Trp-P-2 causing 50% inhibition of human platelet aggregation induced by sodium arachidonate were 15 and 25 μM, respectively. The heterocyclic amines examined had no significant effects on human polymorphonuclear leucocyte aggregation. Moreover, radiochemical studies of arachidonate metabolism showed that Trp-P-1 and Trp-P-2 inhibited, in a dose-dependent manner, the formation of cyclooxygenase products in platelets induced by sodium arachidonate. These results indicate that Trp-P-1 and Trp-P-2 have potent inhibitory effects on prostaglandin endoperoxide synthetase in the stimulus-reaction system of human platelets.