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. 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 days, and used for experiments 7 days 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 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.