Decreased availability of intestinal dopamine in transmural colitis may relate to inhibitory effects of interferon-gamma upon L-DOPA uptake.
OBJECTIVE
The present study aimed to evaluate the relationship between intestinal inflammation, interferon-gamma (IFN-gamma) levels and intestinal levels of dopamine, its precursor l-3,4-dihydroxyphenylalanine (L-DOPA), and the activity of aromatic L-amino acid decarboxylase (AADC) activity along the digestive tract in a rat experimental model of colitis.


METHODS
Colitis was induced by rectal administration of 2,4,6-trinitrobenzene sulphonic acid (TNBS). Catechol derivatives were assayed by means of HPLC-EC.


RESULTS
It is shown that dopamine and noradrenaline levels in the distal colon (inflamed mucosa), but not in the ileum (non-inflamed mucosa), of TNBS-treated rats were markedly lower than in control animals. A slight decrease in L-DOPA tissue levels, no changes in AADC activity and an increase in plasma IFN-gamma levels accompanied this decrease in dopamine levels. Exposure of Caco-2 cells, a human intestinal epithelial cell line, to human IFN-gamma resulted in a concentration-dependent and long-lasting inhibition of L-DOPA uptake, which most likely explains the decrease in dopamine levels in the inflamed mucosa.


CONCLUSIONS
Changes in tissue levels of noradrenaline and dopamine in experimental colitis in the rat follow a similar pattern to that observed in patients with Crohn's disease and ulcerative colitis. In this model of experimental colitis, the decrease in dopamine levels is most likely explained by the inhibitory effect of IFN-gamma on L-DOPA uptake by intestinal epithelial cells.
Magro
F
F
Institute of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal.
Fraga
S
S
Ribeiro
T
T
Soares-da-Silva
P
P
D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism; D018938:Caco-2 Cells; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003092:Colitis / Q000378:metabolism*; D003106:Colon / Q000378:metabolism; D004298:Dopamine / Q000032:analysis*; D006801:Humans; D007082:Ileum / Q000378:metabolism; D007371:Interferon-gamma / Q000097:blood / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007980:Levodopa / Q000493:pharmacokinetics*; D008297:Male; D009638:Norepinephrine / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D014302:Trinitrobenzenesulfonic Acid
D007980:Levodopa; D007371:Interferon-gamma; D014302:Trinitrobenzenesulfonic Acid; D001142:Aromatic-L-Amino-Acid Decarboxylases; D004298:Dopamine; D009638:Norepinephrine