Impaired gastrocolonic response and peristaltic reflex in slow-transit constipation: role of 5-HT3 pathways

Abstract

Colonic motility is modulated by the 5-hydroxytryptamine (5-HT)3-dependent gastrocolonic response and 5-HT3-independent peristaltic reflex. We compared descending colon tone responses to antral distension, duodenal lipid perfusion, and colonic distension after double-blind placebo or granisetron in 13 healthy volunteers and nine slow-transit constipated patients. Antral distension (100–300 ml) and duodenal lipids (3 kcal/min) evoked increases in colon tone in volunteers, which were blunted in constipated patients ( P < 0.05). Granisetron (10 μg/kg) reduced responses to antral distension and lipids in volunteers and to lipids in constipated patients ( P < 0.05). The ascending contraction of the peristaltic reflex was blunted in constipated patients ( P < 0.05), whereas descending responses were similar. Granisetron did not modify the peristaltic reflex. Colonic responses to bethanechol were similar in patients and volunteers. In conclusion, antral distension- and duodenal lipid-activated gastrocolonic responses and ascending contractions of the peristaltic reflex are impaired with slow-transit constipation with loss of both 5-HT3-dependent and -independent function. Thus abnormalities of neural reflex modulation of colonic motor function may play pathophysiological roles in slow-transit constipation.