Effects of heterocyclic amines in food on dopamine metabolism in nigro-striatal dopaminergic neurons.

We investigated the effects of 14 heterocyclic amines in food on nigro-striatal dopaminergic neurons. Among 14 compounds tested, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) caused substantial decreases in 3,4-dihydroxy-phenylalanine (DOPA) formation in striatal tissue slice system. When Trp-P-1 or Trp-P-2 was unilaterally infused in the rat striatum by an in vivo micro-dialysis technique, both compounds produced a transient increase of dopamine (DA) and continuous decreases in the metabolites, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in the perfusate. This suggests that the two compounds inhibit monoamine oxidase (MAO) in vivo. Indeed they were found to be very potent inhibitors of MAO in vitro. Systemic administration of Trp-P-1 to C57 Black mice caused a marked decrease of DOPAC content and a significant increase of DA in the striatum, indicating inhibition of MAO in vivo. These results suggest that Trp-P-1 and Trp-P-2 contained in food could alter the metabolism of DA in the brain.