Upregulation of mucosal 5-HT3 receptors is involved in restoration of colonic transit after pelvic nerve transection.

BACKGROUND: Colonic dysfunction occurs after pelvic autonomic nerve damage. The enteric nervous system can compensate. We investigated the role of mucosal serotonin receptors, 5-HT(3) and 5-HT(4) , in the colonic motility restoration over 2 weeks after parasympathetic pelvic nerve transection in a rat model. METHODS: Male Sprague-Dawley rats underwent pelvic nerve transection or sham operation. Colonic transit was expressed as the geometric center of (51) Cr distribution. Mucosal 5-HT(3) and 5-HT(4) receptor expression was evaluated by Western blot. Intraluminal pressure increase was measured after 5-HT(3) (ondansetron) or 5-HT(4) receptor antagonist (GR125487) administration in vitro in sham and denervated distal colons. KEY RESULTS: At 2 weeks, colonic transit in the denervated group was 30% slower compared to the sham group (P < 0.01). At 1 and 2 weeks, 5-HT(3) receptor expression was increased two-fold in the denervated group, compared to shams (P < 0.05). A three-fold smaller dose of ondansetron was required in denervated tissues to inhibit intraluminal pressure rise than in sham colons (P < 0.01). There was no difference in the expression of 5-HT(4) receptor or the response to GR125487 in denervated vs sham colons. CONCLUSIONS & INFERENCES: Colonic motility was restored to approximately 70% normal over 1 week without further improvement at 2 weeks. Enteric nervous system compensated by upregulating mucosal 5-HT(3,) but not 5-HT(4,) receptors.

Effects of autonomic nerve stimulation on colorectal motility in rats.

BACKGROUND: Several disease processes of the colon and rectum, including constipation and incontinence, have been associated with abnormalities of the autonomic nervous system. However, the autonomic innervation to the colon and rectum are not fully understood. The aims of this study were to investigate the effect of stimulation of vagus nerves, pelvic nerves (PN) and hypogastric nerves (HGN) on colorectal motility in rats. METHODS: Four strain gauge transducers were implanted on the proximal colon, mid colon, distal colon and rectum to record circular muscle contractions in rats. Electrical stimulation was administered to the efferent distal ends of the cervical vagus nerve, PN and HGN. Motility index (MI) was evaluated before and during stimulation. KEY RESULTS: Electrical stimulation (5-20 Hz) of the cervical vagus elicited significant contractions in the mid colon and distal colon, whereas less pronounced contractions were observed in the proximal colon. Pelvic nerves stimulation elicited significant contractions in the rectum as well as the mid colon and distal colon. Atropine treatment almost completely abolished the contractions induced by vagus nerve and PN stimulation. Hypogastric nerves stimulation caused relaxations in the rectum, mid colon and distal colon. The relaxations in response to HGN stimulation were abolished by propranolol. CONCLUSIONS & INFERENCES: Vagal innervation extends to the distal colon, while the PN has projections in the distribution of the rectum through the mid colon. This suggests a pattern of dual parasympathetic innervation in the left colon. Parasympathetic fibers regulate colorectal contractions via muscarinic receptors. The HGN mainly regulates colorectal relaxations via beta-adrenoceptors.