Increase in neurokinin-1 receptor-mediated colonic motor response in a rat model of irritable bowel syndrome.
OBJECTIVE
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 micromol/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 N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 micromol/L) augmented the NK1R agonist-induced contraction only in normal rat colon.


CONCLUSIONS
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.
La
Jun-Ho
JH
Department of Physiology, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
Kim
Tae-Wan
TW
Sung
Tae-Sik
TS
Kim
Hyn-Ju
HJ
Kim
Jeom-Yong
JY
Yang
Il-Suk
IS
D019342:Acetic Acid; D000818:Animals; D003092:Colitis / Q000139:chemically induced; D003106:Colon / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D005769:Gastrointestinal Motility / Q000502:physiology; D043183:Irritable Bowel Syndrome / Q000473:pathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000502:physiology*
D018040:Receptors, Neurokinin-1; D019342:Acetic Acid; D019331:NG-Nitroarginine Methyl Ester