OBJECTIVETo evaluate the roles of enteric nervous system neurotransmitters, nitric oxide (NO), substance P (SP) and vasoactive intestinal polypeptide (VIP), and interstitial cells of Cajal (ICC) in the colon in slow transit constipation in rats.

METHODSThirty-two healthy Wistar rats were randomly assigned to control and constipated groups. In the constipated group, the rats were daily administered with diphenoxylate (8 mg/kg) to develop slow transit constipation, while the control rats were fed with water. The number and the weight of fecal granule and the body weight of rats were recorded every 5 days for 90 days. Transit functions of intestinal movement were examined by an activated charcoal suspension pushing test one week after stopping the administration of diphenoxylate. The levels of NO and SP in the colonic mucosa were measured by nitrate reductase methods and ELISA respectively. The distribution of VIP and ICC positive cells confirmed with symbolic c-kit+ cells in the colonic wall were observed by immunohistochemical methods.

RESULTSThe daily number of fecal granule in the constipated group was significantly less than that in the control group (P<0.01). The mean weight of each fecal granule in the constipated group was significantly higher than that in the control group (P<0.01). The discharge time of the first granule of black faeces in the constipated group (430.2+/- 132.1 min) was significantly longer than that in the control group (337.2+/- 74.7 min; P<0.05). There were no significant differences in NO and SP levels and the density of VIP positive cells in the distal colonic segment between the two groups. The number of c-kit+ cells in the distal colonic wall in the constipated group was significantly reduced compared with that in the control group (P<0.05).

CONCLUSIONSThe reduction of ICC number in the distal colon may be contributed to the pathogenesis of slow transit constipation in rats.