Increase in neurokinin-1 receptor-mediated colonic motor response in a rat model of irritable bowel syndrome

Jun-Ho La, Tae Wan Kim, Tae Sik Sung, Hyn Ju Kim, Jeom Yong Kim, Il Suk Yang

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Abstract

Aim: Irritable bowel syndrome (IBS) is a functional bowel disorder. Its major symptom is bowel dysmotility, yet the mechanism of the symptom is poorly understood. Since the neurokinin-1 receptor (NK1R)-mediated signaling in the gut is important in the control of normal bowel motor function, we aimed to investigate whether the NK1R-mediated bowel motor function was altered in IBS, using a rat IBS model that was previously reported to show colonic dysmotility in response to restraint stress. Methods: IBS symptoms were produced in male Sprague-Dawley rats by inducing colitis with acetic acid. Rats were left to recover from colitis for 6 d, and used for experiments 7 d post-induction of colitis. Motor activities of distal colon were recorded in vitro. Results: The contractile sensitivity of isolated colon to a NK1R agonist [Sar9,Met(O2 11]-substance P (1-30 nmol/L) was higher in IBS rats than that in normal rats. After the enteric neurotransmission was blocked by tetrodotoxin (TTX, 1 μmol/L), the contractile sensitivity to the NK1R agonist was increased in normal colon but not in IBS rat colon. The NK1R agonist-induced contraction was not different between the two groups when the agonist was challenged to the TTX-treated colon or the isolated colonic myocytes. A nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME, 100 μmol/L) augmented the NK1R agonist-induced contraction only in normal rat colon. Conclusion: These results suggest that the NK1R-meidated colonic motor response is increased in IBS rats, due to the decrease in the nitrergic inhibitory neural component.

Original languageEnglish (US)
Pages (from-to)237-241
Number of pages5
JournalWorld Journal of Gastroenterology
Volume11
Issue number2
StatePublished - Jan 14 2005
Externally publishedYes

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Keywords

  • Irritable bowel sydrome
  • Neurokinin-1 receptor

ASJC Scopus subject areas

  • Gastroenterology

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