Dopamine formation, from its immediate precursor 3,4-dihydroxyphenylalanine, along the rat digestive tract.
The formation of dopamine, from L-3,4-dihydroxyphenylalanine (L-dopa), in fragments of non-glandular and glandular stomach, duodenum, jejunum, ileum and proximal and distal colon of the rat was examined. The deamination of newly-formed dopamine into 3,4-dihydroxyphenylacetic acid (dopac) was also studied. The synthesis of dopamine in tissues incubated with 500 microM L-dopa for 20 min in conditions of catechol-O-methyltransferase (Comt) inhibition was found to be in the duodenum, jejunum and ileum 2-fold that in the proximal colon, 6-fold that in the glandular stomach and 120-fold that in the non-glandular stomach and distal colon. The formation of dopac in these tissues followed the pattern of amine formation. In the jejunum, the formation of dopamine and dopac was found to be dependent on the concentration of L-dopa (50 to 5000 microM) used. In another set of experiments, it was found that the formation of dopamine in jejunal segments loaded with increasing concentrations of L-dopa (50, 100 and 500 microM) was a time-dependent process. The rate constant (k) of formation of dopamine as a function of time was found to be similar (0.050 +/- 0.005) with either concentration of L-dopa; the rate constant of dopac formation in these experiments was, in contrast, found to be greater at the highest concentrations of L-dopa (100 and 500 microM). Aromatic L-amino acid decarboxylase (Aaad) activity determined in homogenates of the jejunal mucosa was found to be twice that observed in homogenates of the remaining jejunal wall (muscular).(ABSTRACT TRUNCATED AT 250 WORDS)
Vieira-Coelho
M A
MA
Department of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal.
Soares-da-Silva
P
P
D000818:Animals; D004064:Digestive System / Q000378:metabolism*; D004295:Dihydroxyphenylalanine / Q000378:metabolism*; D004298:Dopamine / Q000096:biosynthesis*; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism; D007583:Jejunum / Q000378:metabolism; D007980:Levodopa / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D007980:Levodopa; D004295:Dihydroxyphenylalanine; D004298:Dopamine; D009638:Norepinephrine