ltered 5-Hydroxytryptamine Signaling in Patients With onstipation- and Diarrhea-Predominant Irritable Bowel yndrome

5 p P ackground & Aims: Evidence suggests that postpranial platelet-depleted plasma 5-hydroxytryptamine (5T) concentrations may be abnormal in irritable bowel yndrome (IBS). However, interpretation of the data has een hampered by the variable methodology and rather mall numbers used in previous studies. Therefore, the im of this study was to measure concentrations of latelet-depleted plasma 5-HT and its metabolite 5-HIAA nder fasting and fed conditions in a large group of atients with diarrhea-predominant (d-) and constipaion-predominant (c-) IBS, compared with controls. The atio of plasma 5-HIAA:5-HT and platelet stores was also ssessed. Methods: Twenty-nine c-IBS patients (aged, 9–53 years), 55 d-IBS patients (aged, 19–52 years), nd 35 healthy volunteers (aged, 18–46 years) had latelet-depleted plasma 5-HT/5-HIAA concentrations easured using reverse-phase, high-performance liquid hromatography with fluorimetric detection before and fter a standard meal. Results: d-IBS patients had raised latelet-depleted plasma 5-HT concentrations under asting and fed conditions (P < .05). However, the postrandial relative to fasting concentration was similar to ontrols. In contrast, c-IBS patients failed to show an ncrease in platelet-depleted plasma 5-HT concentration ith meal ingestion compared with controls (P < .01). -IBS was associated with decreased 5-HIAA (P < .01) ut normal 5-HIAA:5-HT ratio and d-IBS with normal -HIAA concentrations but reduced 5-HIAA:5-HT ratio (P .005). C-IBS but not d-IBS patients had increased latelet 5-HT. Conclusions: These results support the oncept that d-IBS is characterized by reduced 5-HT euptake, whereas impaired release may be a feature of -IBS. These results also provide a rational basis for urrent pharmacologic approaches involving modulation f different 5-HT receptors in cand d-IBS.