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-HT3 and 5-HT4, 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 51Cr distribution. Mucosal 5-HT3 and 5-HT4 receptor expression was evaluated by Western blot. Intraluminal pressure increase was measured after 5-HT3 (ondansetron) or 5-HT4 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-HT3 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-HT4 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-HT3, but not 5-HT4, receptors.