Abnormalities of 5-hydroxytryptamine metabolism in irritable bowel syndrome.
OBJECTIVE
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 < .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.
Dunlop
Simon P
SP
Division of Gastroenterology, University Hospital, Nottingham NG7 2UH, UK.
Coleman
Nicholas S
NS
Blackshaw
Elaine
E
Perkins
Alan C
AC
Singh
Gulzar
G
Marsden
Charles A
CA
Spiller
Robin C
RC
D000328:Adult; D015415:Biomarkers / Q000032:analysis; D001707:Biopsy, Needle; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D004032:Diet; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000473:pathology; D043183:Irritable Bowel Syndrome / Q000175:diagnosis* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010528:Peristalsis / Q000502:physiology; D011336:Probability; D011379:Prognosis; D012016:Reference Values; D012680:Sensitivity and Specificity; D012701:Serotonin / Q000032:analysis / Q000378:metabolism*; D012720:Severity of Illness Index
D015415:Biomarkers; D012701:Serotonin