Comparison of 5-hydroxytryptophan signaling pathway characteristics in diarrhea-predominant irritable bowel syndrome and ulcerative colitis.

OBJECTIVE

To study differences in the visceral sensitivity of the colonic mucosa between patients with diarrhea-predominant irritable bowel syndrome (IBS-D) and those with ulcerative colitis (UC) in remission and to relate these differences with changes in the 5-hydroxytryptophan (5-HT) signaling pathway.

METHODS

Gastrointestinal symptoms were used to determine the clinical symptom scores and rectal visceral sensitivity of patients with IBS-D and patients with UC in remission. Blood levels of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) were measured using an HPLC-electrochemical detection system. The levels of 5-HT 3 receptor (3R), 4R, and 7R mRNAs in colonic biopsy samples were detected using reverse transcription-polymerase chain reaction. The protein expression of TPH1 was analyzed by Western blot and immunohistochemistry.

RESULTS

Abdominal pain or discomfort, stool frequency, and the scores of these symptoms in combination with gastrointestinal symptoms were higher in the IBS-D and UC groups than in the control groups. However, no significant differences were observed between the IBS-D and UC remission groups. With respect to rectal visceral sensitivity, the UC remission and IBS-D groups showed a decrease in the initial perception threshold, defecating threshold and pain threshold. However, these groups exhibited significantly increased anorectal relaxation pressure. Tests examining the main indicators of the 5-HT signaling pathway showed that the plasma 5-HT levels, 5-HIAA concentrations, TPH1 expression in the colonic mucosa, and 5-HT3R and 5-HT5R expression were increased in both the IBS-D and the UC remission groups; no increases were observed with respect to 5-HT7R expression.

CONCLUSIONS

The IBS-D and UC groups showed similar clinical symptom scores, visceral sensitivity, and levels of serotonin signaling pathway indicators in the plasma and colonic mucosa. However, the pain threshold and 5-HT7R expression in the colonic mucosa were significantly different between these groups. The results reveal that (1) IBS-D and UC are related to visceral sensitivity pathogenesis and the clinical manifestations of these conditions and (2) the observed differences in visceral hypersensitivity are possibly due to differences in levels of the 5-HT7 receptor, a component of the 5-HT signaling pathway.