Food-Derived Heterocyclic Amines as Potent Inhibitors of Catecholamine Metabolism

Abstract

Following the discovery of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine as a neurotoxin that produces symptoms similar to those of parkinsonism in humans,¹ many naturally-occurring or synthesized compounds have been proposed as putative neurotoxins. Among carboline derivatives, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-imethyl-5H-pyrido[4,3-b]indole (Trp-P-2) are produced by pyrolysis of tryptophan in food.² It was found from in vitro and acute in vivo experiments that Trp-P-1 and Trp-P-2 reduced DOPA formation in rat striatal tissue slices and were potent inhibitors of monoamine oxidse [MAO; monoamine: oxygen oxidoreductase (deaminating), EC 1.4.3.4].³ To examine chronic in vivo effects of Trp-P-1 and Trp-P-2 on catecholamine metabolism, was used a clonal rat pheochromocytoma cell line, PC12h, as a model of dopamine (DA) neurons. The cells were cultured in the presence of Trp-P-1 and Trp-P-2 for 6 days, and their effects on activity of the enzymes involved in catecholamine metabolism, such as tyrosine hydroxylase [TH; tyrosine tetra-hydropteridine: oxygen oxidoreductase (3-hydroxylase), EC 1.14.16.2] and aromatic L-aminoacid decarboxylase (AADC; aromatic L-aminoacid carboxy-lyase, EC 4.1.1.28), were examined. Using PC12h cells, we also examined whether these amines may be taken up into DA neurons selectively.