3-amino-1-4-dimethyl-5h-pyrido(4-3-b)indole and indatraline

3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), which is a tryptophan pyrolysate formed during cooking, induces apoptosis in rat splenocytes, thymocytes, and hepatocytes. In this study, we investigated whether Trp-P-1 is transported into these cells and causes apoptosis. Trp-P-1 was immediately incorporated into rat splenocytes, thymocytes, and hepatocytes in a dose- and time-dependent manner. Dopamine and serotonin significantly competed with the uptake of Trp-P-1 into these cells, and nomifensine and indatraline, which are inhibitors of dopamine- and serotonin-transporters, respectively, markedly suppressed the uptake of Trp-P-1. On the other hand, amino acids including tryptophan did not compete with Trp-P-1. Inhibition of monoamine transporters using nomifensine and indatraline partially suppressed Trp-P-1-induced cell death in these cells. In hepatocytes, the inhibition of transporters prevented Trp-P-1-induced morphological changes and activation of caspase-3. These results demonstrated that Trp-P-1 is incorporated into the cells through monoamine transporters and induces apoptosis.

Topics: Animals; Apoptosis; Binding, Competitive; Biological Transport; Carbolines; Caspase 3; Caspases; Cells, Cultured; Dopamine Uptake Inhibitors; Enzyme Activation; Hepatocytes; Indans; Male; Membrane Transport Modulators; Membrane Transport Proteins; Methylamines; Nomifensine; Rats; Rats, Wistar; Selective Serotonin Reuptake Inhibitors; Spleen; Thymus Gland; Time Factors