Original articles
Abnormalities of 5-hydroxytryptamine metabolism in irritable bowel syndrome

Presented in abstract form at the American Gastroenterology Association meeting, New Orleans, Louisiana May, 2004.
https://doi.org/10.1016/S1542-3565(04)00726-8Get rights and content

Background & Aims: 5-hydroxytryptamine-3 (5-HT3) receptor antagonists improve symptoms in patients with diarrhea-predominant irritable bowel syndrome (D-IBS), 5-HT4 agonists help those with constipation-predominant IBS (C-IBS). These data suggest excess or deficiency in 5-HT in D-IBS or C-IBS, respectively. Mucosal 5-HT-containing enterochromaffin cells (EC) are increased in postinfectious IBS (PI-IBS). Our aim was to define the postprandial release of 5-HT in PI-IBS and C-IBS patients and to relate this to mucosal 5-HT turnover. Methods: Fifteen PI-IBS patients with diarrhea-predominant symptoms, 15 C-IBS patients, and 15 healthy controls underwent serial (platelet-poor) plasma 5-HT measurement for 3 hours after a standard 520-kcal meal. Rectal biopsy specimens were assayed for 5-HT and its metabolite 5-hydroxindoleacetic acid (5-HIAA). Colonic transit was measured using radio-opaque markers. Results: Colonic transit was prolonged in C-IBS patients (mean ± SEM) (49.4 ± 3.8 h) compared with PI-IBS (26.7 ± 4.5) and control patients (34.1 ± 4.5) (P < .02). Release of 5-HT assessed by area under the curve (AUC) of platelet-poor plasma 5-HT from 0 to 180 minutes postprandially was significantly lower in C-IBS patients (2593 ± 309 mmol/L · min) compared with P-IBS (5623 ± 721) and control patients (4822 ± 598) (P < .001). PI-IBS patients showed significantly higher peak postprandial plasma 5-HT values (median, range) (71.7, 43.4–125.3) ng/L compared with C-IBS patients (31.2, 15.2–40.5) and control patients (43.6, 26.7–50.1) (P < .01). Mucosal 5-HT turnover as assessed by mucosal 5-HIAA/5-HT ratio was decreased in both C-IBS and PI-IBS patients, .14 (.01–.6) and .21 (.02–2.5), respectively, compared with control patients 1.12 (.17–3.1) (P < .002). Conclusions: C-IBS patients show impaired postprandial 5-HT release whereas PI-IBS patients have higher peak levels, abnormalities that may be related to their different symptoms.

Section snippets

IBS patients and healthy controls

Thirty patients who met the Rome II criteria for IBS23 and who had completed a full negative evaluation for other diseases in the University Hospital, Nottingham Gastroenterology Outpatient Clinic were included. Over the duration of the study 133 IBS patients were seen. After applying the exclusions listed later there were 51 eligible patients, of whom 30 chose to take part. The most common reason for not participating was inability to take time off from work. The evaluation included a detailed

Demographics and bowel symptoms

The age range within each of the 3 groups was similar (range, 18–59 y) and there were no significant differences among the groups. As shown, C-IBS patients had less frequent, harder stools whereas the PI-IBS patients had more frequent, looser stools, but the frequency of abdominal pain was similar in both IBS groups (P = .4) (Table 1). There were significantly more men in the PI-IBS group and, consequently, the mean weight was highest in this group. There was a trend for bloating to be more

Discussion

This study directly compared postprandial 5-HT release and mucosal 5-HT metabolism in various subtypes of IBS. Our most significant finding was uniformly decreased postprandial levels of plasma 5-HT in C-IBS patients. This decreased release was associated with significantly delayed transit. In an attempt to define the causes of this decreased release we examined mucosal EC cells within a rectal biopsy specimen. We found that C-IBS patients tended to have increased amounts of 5-HT per cell when

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