Faculty Collaboration Database

Upregulation of mucosal 5-HT3 receptors is involved in restoration of colonic transit after pelvic nerve transection. Neurogastroenterol Motil 2012 May;24(5):472-8, e218

Date

02/07/2012

Pubmed ID

22304456

DOI

10.1111/j.1365-2982.2012.01890.x

Scopus ID

2-s2.0-84862811573 (requires institutional sign-in at Scopus site)   4 Citations

Abstract

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.

Author List

Gribovskaja-Rupp I, Takahashi T, Ridolfi T, Kosinski L, Ludwig K

Authors

Kirk A. Ludwig MD Chief, Professor in the Surgery department at Medical College of Wisconsin
Timothy J. Ridolfi MD, MS, FACS Associate Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Blotting, Western
Chromium Radioisotopes
Colon
Denervation
Dose-Response Relationship, Drug
Enteric Nervous System
Gastrointestinal Transit
In Vitro Techniques
Indoles
Intestinal Mucosa
Male
Ondansetron
Pelvis
Peripheral Nerves
Rats
Rats, Sprague-Dawley
Receptors, Serotonin, 5-HT3
Receptors, Serotonin, 5-HT4
Serotonin 5-HT3 Receptor Antagonists
Serotonin 5-HT4 Receptor Antagonists
Serotonin Antagonists
Sulfonamides
Up-Regulation