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

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

doi:10.1111/j.1365-2982.2012.01890.x

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

Journal article

Peer reviewed

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

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

Neurogastroenterology and motility, Vol.24(5), pp.472-478

05/2012

DOI: 10.1111/j.1365-2982.2012.01890.x

PMID: 22304456

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Abstract

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. 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. 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. 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.

Up-Regulation

Intestinal Mucosa - metabolism

Ondansetron - pharmacology

Colon - physiology

Receptors, Serotonin, 5-HT4 - biosynthesis

Male

Pelvis - innervation

Dose-Response Relationship, Drug

Serotonin 5-HT4 Receptor Antagonists - pharmacology

Peripheral Nerves - physiology

Receptors, Serotonin, 5-HT3 - biosynthesis

Indoles - pharmacology

Receptors, Serotonin, 5-HT3 - drug effects

Rats

Gastrointestinal Transit - physiology

Serotonin Antagonists - pharmacology

Sulfonamides - pharmacology

Rats, Sprague-Dawley

Blotting, Western

Chromium Radioisotopes

Animals

Receptors, Serotonin, 5-HT3 - physiology

Serotonin 5-HT3 Receptor Antagonists - pharmacology

Enteric Nervous System - physiology

In Vitro Techniques

Denervation

Details

Title: Subtitle: Upregulation of mucosal 5-HT3 receptors is involved in restoration of colonic transit after pelvic nerve transection
Creators: I Gribovskaja-Rupp - Department of Surgery, Medical College of Wisconsin, Clement J Zablocki VA Medical Center, Milwaukee, WI, USA
T Takahashi
T Ridolfi
L Kosinski
K Ludwig
Resource Type: Journal article
Publication Details: Neurogastroenterology and motility, Vol.24(5), pp.472-478
Publisher: England
DOI: 10.1111/j.1365-2982.2012.01890.x
PMID: 22304456
ISSN: 1350-1925
eISSN: 1365-2982
Language: English
Date published: 05/2012
Academic Unit: Surgery
Record Identifier: 9984051570502771

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