Impaired synthesis or cellular storage of norepinephrine, dopamine, and 5-hydroxytryptamine in human inflammatory bowel disease.
The present study was aimed at evaluating the extent of dysfunction of the enteroendocrine and enteric nervous system, as indicated by changes in tissue levels of monoamines (dopamine, DA; norepinephrine, NE; 5-hydroxytryptamine, 5-HT) and their precursors and metabolites in the colonic mucosa of patients afflicted with ulcerative colitis (UC, N = 21) and Crohn's disease (CD, N = 22). In CD, but not in UC, NE tissue levels in both the noninflamed and inflamed colonic mucosa were markedly lower than in control subjects (N = 16). In the inflamed mucosa of CD and in UC patients levels of L-DOPA were twice those in controls. DA levels in the inflamed mucosa of CD and UC patients were markedly lower than in controls. This resulted in significant reductions in DA/L-DOPA tissue ratios, a rough measure of L-amino acid decarboxylase activity. 5-HT levels in the inflamed mucosa of CD and UC patients were markedly lower than in controls. In conclusion, intestinal cellular structures responsible for the synthesis and storage of DA, NE, and 5-HT may have been affected by the associated inflammatory process in both CD and UC.
Magro
F
F
Institute of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal.
Vieira-Coelho
M A
MA
Fraga
S
S
Serrão
M P
MP
Veloso
F Tavarela
FT
Ribeiro
Tomé
T
Soares-da-Silva
P
P
D003093:Colitis, Ulcerative / Q000378:metabolism; D003106:Colon / Q000378:metabolism; D003424:Crohn Disease / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D015212:Inflammatory Bowel Diseases / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*
D012701:Serotonin; D004298:Dopamine; D009638:Norepinephrine