Serotonin transporter function and expression are reduced in mice with TNBS-induced colitis

Neurogastroenterol Motil. 2005 Aug;17(4):565-74. doi: 10.1111/j.1365-2982.2005.00673.x.


Regulated release of serotonin (5-HT) from enterochromaffin (EC) cells activates neural reflexes that are involved in gut motility, secretion, vascular perfusion and sensation. The 5-HT-selective reuptake transporter (SERT) terminates serotonergic signalling in the intestinal mucosa. The aim of this investigation was to determine whether mucosal 5-HT content, release, and/or reuptake are altered in a murine model of immune cell-mediated colitis. Experiments were conducted 6 days after colitis was induced by 2,4,6-trinitrobenzene sulfonic acid, a time point when macroscopic and histological damage scores indicated significant inflammation. During inflammation, SERT transcript levels and immunoreactivity were reduced, and the uptake of [3H] 5-HT was impaired. Increases in mucosal 5-HT content and the number of 5-HT-immunoreactive mast cells in the lamina propria were also detected in the inflamed region, whereas EC cell numbers did not change. Mucosal 5-HT released under basal and stimulated conditions was unchanged in animals with colitis. These data suggest that murine colitis alters 5-HT signalling by increasing 5-HT availability through decreased 5-HT uptake by mucosal epithelial cells. These findings support the concept that altered 5-HT signalling could be a contributing factor in altered gut function and sensitivity in inflammatory bowel disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Colitis / chemically induced
  • Colitis / metabolism*
  • Colitis / pathology
  • Disease Models, Animal
  • Enterochromaffin Cells / metabolism
  • Immunohistochemistry
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Mast Cells / metabolism
  • Membrane Glycoproteins / metabolism*
  • Membrane Transport Proteins / metabolism*
  • Mice
  • Nerve Tissue Proteins / metabolism*
  • RNA, Messenger / analysis
  • Serotonin / metabolism*
  • Serotonin Plasma Membrane Transport Proteins
  • Transcription, Genetic
  • Trinitrobenzenesulfonic Acid / toxicity


  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • RNA, Messenger
  • Serotonin Plasma Membrane Transport Proteins
  • Slc6a4 protein, mouse
  • Serotonin
  • Trinitrobenzenesulfonic Acid