Food-Derived Heterocyclic Amines as Potent Inhibitors of Catecholamine Metabolism
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 188.8.131.52].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 184.108.40.206] and aromatic L-aminoacid decarboxylase (AADC; aromatic L-aminoacid carboxy-lyase, EC 220.127.116.11), were examined. Using PC12h cells, we also examined whether these amines may be taken up into DA neurons selectively.
KeywordsTyrosine Hydroxylase Heterocyclic Amine Minimal Sample Preparation Tyrosine Hydroxylase Activity Catecholamine Metabolism
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