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.


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
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.
Department of Surgery, Medical College of Wisconsin, Clement J Zablocki VA Medical Center, Milwaukee, WI, USA.
I
I
Gribovskaja-Rupp
T
T
Takahashi
T
T
Ridolfi
L
L
Kosinski
K
K
Ludwig
D000818:Animals; D015153:Blotting, Western; D002860:Chromium Radioisotopes; D003106:Colon / Q000502:physiology*; D003714:Denervation; D004305:Dose-Response Relationship, Drug; D017615:Enteric Nervous System / Q000502:physiology; D005772:Gastrointestinal Transit / Q000502:physiology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D017294:Ondansetron / Q000494:pharmacology; D010388:Pelvis / Q000294:innervation; D010525:Peripheral Nerves / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044406:Receptors, Serotonin, 5-HT3 / Q000096:biosynthesis* / Q000187:drug effects / Q000502:physiology; D044422:Receptors, Serotonin, 5-HT4 / Q000096:biosynthesis; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000494:pharmacology; D058832:Serotonin 5-HT4 Receptor Antagonists / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D015854:Up-Regulation
D002860:Chromium Radioisotopes; D007211:Indoles; D044406:Receptors, Serotonin, 5-HT3; D058831:Serotonin 5-HT3 Receptor Antagonists; D058832:Serotonin 5-HT4 Receptor Antagonists; D012702:Serotonin Antagonists; D013449:Sulfonamides; D044422:Receptors, Serotonin, 5-HT4; D017294:Ondansetron; C082871:GR 113808