Abnormalities of 5-hydroxytryptamine metabolism in irritable bowel syndrome

Background & Aims: 5-hydroxytryptamine-3 (5-HT 3 ) receptor antagonists improve symptoms in patients with diarrhea-predominant irritable bowel syndrome (D-IBS), 5-HT 4 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 P P P 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.