SERT and TPH-1 mRNA expression are reduced in irritable bowel syndrome patients regardless of visceral sensitivity state in large intestine.
Colorectal visceral hypersensitivity has been demonstrated in a subset of irritable bowel syndrome (IBS) patients. Serine protease and serotonergic signaling modulate gastrointestinal visceral sensitivity. We evaluated whether altered mucosal serine protease and serotonergic pathway components are related to rectal visceral hypersensitivity in IBS patients. Colorectal mucosal biopsies of 23 IBS patients and 15 controls were collected. Gene transcripts of protease-activated receptor (PAR)-2, trypsinogen IV, tryptophan hydroxylase (TPH)-1, and serotonin reuptake transporter (SERT) were quantified using real-time polymerase chain reaction. Substance P and 5-HT contents were measured by ELISA. The number of enterochromaffin cells, mast cells, and intraepithelial lymphocytes was determined using immunohistochemistry. Rectal visceral sensitivity was determined in IBS patients using barostat programmed for phasic ascending distension. Rectal hypersensitivity (+) and (-) IBS patients showed lower TPH-1 and SERT mRNA levels in the rectum compared with controls (P ≤ 0.05). Rectal hypersensitivity (+) IBS patients (n = 12) showed lower TPH-1 mRNA level in the sigmoid compared with controls (P = 0.015). No significant differences were observed in PAR-2 and trypsinogen IV expression between controls and IBS patients. Rectal substance P content was increased in IBS patients compared with controls (P = 0.045). No significant differences were found in transcript levels, cell counts, and substance P and 5-HT contents between rectal hypersensitivity (+) and (-) IBS patients. In conclusion, regardless of visceral hypersensitivity state, several serotonergic signaling components are altered in IBS patients.
Gastrointestinal Research Unit, Department of Gastroenterology, University Medical Centre Utrecht, Utrecht, The Netherlands. angelekerckhoffs@hotmail.com
Angèle P M
AP
Kerckhoffs
José J M
JJ
ter Linde
Louis M A
LM
Akkermans
Melvin
M
Samsom
D000328:Adult; D000368:Aged; D015536:Down-Regulation; D006801:Humans; D007420:Intestine, Large / Q000503:physiopathology*; D043183:Irritable Bowel Syndrome / Q000150:complications / Q000503:physiopathology*; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D044464:Receptor, PAR-2 / Q000235:genetics / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D014365:Tryptophan Hydroxylase / Q000235:genetics / Q000378:metabolism*; D059265:Visceral Pain / Q000209:etiology / Q000503:physiopathology*; D055815:Young Adult
D012333:RNA, Messenger; D044464:Receptor, PAR-2; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; C497467:TPH1 protein, human; D014365:Tryptophan Hydroxylase