Protection from DNBS-induced colitis by the tachykinin NK1 receptor antagonist SR140333 in rats

Inflammation is known to be associated with changes in tachykinin expression both in human and animal models: substance P and NK1 receptor expression are increased in patients with inflammatory bowel disease, and similar changes are reported in experimental models of inflammation. We investigated the effect of the tachykinin NK1 receptor antagonist SR140333 (10 mg/kg orally) on 2,4-dinitrobenzene sulfonic acid (DNBS)induced colitis in rats. Colonic damage was assessed by means of macroscopic and microscopic scores, myeloperoxidase activity (MPO) and TNF-alpha tissue levels on day 6 after induction of colitis. An enzyme immunoassay technique was used to measure colonic substance P levels. DNBS administration impaired body weight gain and markedly increased all inflammatory parameters as well as colonic tissue levels of substance P. Treatment with SR140333 significantly counteracted the impairment in body weight gain, decreased macroscopic and histological scores and reduced colonic myeloperoxidase activity and TNF-alpha tissue levels. Colonic tissue levels of substance P were also reduced by SR140333, although this effect did not reach statistical significance. In conclusion, treatment with SR140333 protects from DNBS-induced colitis in rats. These results suggest a role for NK1 receptors and substance P in the development of intestinal inflammation and indicate tachykinin receptors. as a potential pharmacological target in the treatment of inflammatory bowel disease. (C) 2008 Elsevier B.V. All rights reserved.