Article Text

Download PDFPDF
Divergent changes to muscarinic and serotonergic signalling following colitis
  1. R W Wells,
  2. M G Blennerhassett
  1. Gastrointestinal Diseases Research Unit, Queen’s University, Kingston, Ontario, Canada
  1. Correspondence to:
    Professor M G Blennerhassett
    Gastrointestinal Diseases Research Unit, Queen’s University, Hotel Dieu Hospital, 166 Brock St, Kingston, Ontario K7L 5G2, Canada;


Background: The altered motility of the inflamed intestine derives in part from changes to the contractility of the intestinal smooth muscle cell. While modifications to the muscarinic receptor system are identified, changes to 5-hydroxytryptamine (5-HT; serotonin) receptors that also mediate contraction are less well studied.

Methods: In the trinitrobenzene sulphonic acid model of rat colitis, we used receptor antagonists to identify changes in receptor utilisation that accompany the selective reversal of the impaired contractile response to acetylcholine (ACh) and 5-HT during colitis (day 4 (D4)) and following resolution of inflammation (day 36 (D36)).

Results: In isolated circular smooth muscle cells, challenged with ACh, the muscarinic 3 receptor (M3R) antagonists 4-DAMP and pF-HSD each showed a 50% decrease in antagonism on D4 while the M2R antagonist methoctramine more than doubled its potency, showing a decreased role of M3R and an increased role of M2R, respectively. These changes were fully reversed by D36. In contrast, the 5-HT2 receptor (5-HT2R) antagonist ketanserin was sharply decreased in effectiveness on D4, with a further decrease by D36, when the contribution of 5-HT2AR was only 22% of control. There were no changes in response to the 5-HT4R antagonist SDZ-205-557 at any time. Western blotting identified decreased expression of 5-HT2AR on D36 versus controls, further supporting the conclusion that the persistence of the impaired response to 5-HT was due to decreased expression of the excitatory 5-HT2AR.

Conclusions: Thus the lasting decrease in receptor expression and resulting impairment of the contractile response will compromise the capacity for an appropriate response to 5-HT, which may contribute to the intestinal dysfunction seen in post-enteritis syndromes.

  • 5-HT, 5-hydroxytryptamine (serotonin)
  • 5-HT#R, serotonin receptor #
  • ACh, acetylcholine
  • BSA, bovine serum albumin
  • CCh, carbachol
  • CSMC, circular smooth muscle cell
  • D0, D4, D36, days post initiation of colitis
  • DMSO, dimethylsulphoxide
  • HPSS, HEPES physiological salt solution
  • IBS, irritable bowel syndrome
  • IP3, inositol 1,4,5 trisphosphate
  • MPO, myeloperoxidase
  • M#R, muscarinic receptor #
  • TBS-T, Tris buffered saline with 0.25% Triton X-100
  • TNBS, trinitrobenzene sulphonic acid
  • acetylcholine
  • circular smooth muscle cell
  • contractility
  • intestine
  • serotonin

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Published online first 13 July 2005

  • Conflict of interest: None declared.