ABSTRACT
Serotonin [5-HT] may play an important role in the regulation of colonic motility in humans. However, Meal ingestion is often associated with exacerbation of gastrointestinal symptoms in subjects with irritable bowel syndrome [IBS]. Abnormalities of 5-HT release after a meal might explain some of the postprandial symptoms associated with the irritable bowel syndrome [IBS]. To assess plasma serotonin [5-HT], 5-hydroxyindole acetic acid [5-HIAA] concentrations, 5-HT turnover, platelet 5-HT stores, and any relationship to symptomatology. In addition, to determine whether patients with different clinical manifestations of IBS have different mucosal disposition of 5-HT. After an overnight fast, 20 healthy female volunteers [aged 21- 46 years] [mean 29.3], and 39 female subjects with diarrhea predominant irritable bowel syndrome [d-IBS] [aged 20-48 years] [mean 31.4], were given a standard carbohydrate meal [457 Kcal]. Platelet depleted plasma 5-HT, and 5-HIAA concentrations for two hours [60 minute intervals] under fasting conditions, and then for a further four hours [30 minute intervals] after standard carbohydrate meal were assessed, together with fasting platelet 5- HT concentrations. IBS symptomatology, in particular abdominal pain and bloating, and urgency to defecate were assessed throughout the study. Colonic mucosal specimens ranging from the ascending colon to the rectum were obtained from patients with diarrhea-predominant and from subjects with normal bowel habit by endoscopic biopsy, the tissue concentrations of 5-HT and its major metabolite, 5-hydroxyindoleacetic acid, were determined by reversed-phase high-performance liquid chromatography with fluorescence detection. When related to fasting level, there was no statistically significant difference in postprandial plasma 5-HT concentrations between d-IBS and healthy subjects. However, when fasting levels were not taken into consideration, d-IBS subjects exhibited higher postprandial plasma 5-HT concentrations compared with healthy subjects [p = 0.040]. Furthermore, d-IBS subjects who exhibited postprandial symptomatology had higher levels of postprandial plasma 5-HT, whether assessed with respect to fasting baseline levels [p = 0.065] or not [p = 0.046], compared with dIBS subjects who did not report postprandial symptomatology. This appeared to be associated with a concomitant increase in plasma 5-HIAA [p = 0.162] but reduction in turnover [0.057]. Also, d-IBS subjects had higher platelet concentrations of 5-HT than healthy subjects [p = 0.009]. The mean mucosal 5-HT concentrations obtained from the rectum regions of the colon. In addition, the overall mean mucosal 5-HT concentrations obtained from patients with d-IBS were significantly [p = <0.05] lower than those obtained from the control subjects. No significant difference were observed in 5-HIAA concentrations among the two groups. These data suggest that postprandial symptomatology may be associated with increased platelet plasma 5-HT concentrations in female subjects with d-IBS. The increased release of 5-HT into plasma leads to depletion of mucosal 5-HT in subjects with d-IBS. The presence of increased platelet stores of 5-HT may act as a useful marker for the diagnosis and management of d-IBS