Lack of beneficial effect of a tachykinin receptor antagonist in experimental colitis

Regulatory Peptides
J L WallaceK A Sharkey

Abstract

Nerves within the wall of the intestine may contribute to inflammatory responses, such as those occurring in inflammatory bowel disease. Studies in an experimental model of colitis have demonstrated that neuromodulation, through chemical sympathectomy or administration of lidocaine, can markedly attenuate granulocyte infiltration and tissue injury. Given the many pro-inflammatory effects of substance P, we have evaluated the effects of a tachykinin receptor (NK-1) antagonist, RP 67580, in models of acute colitis in the rat and guinea pig. While administration of RP 67580 and a second NK-1 antagonist (CP-96,345-1) significantly reduced the infiltration of granulocytes into colonic tissue during the first 12 h after induction of colitis in the rat, repeated administration of RP 67580 over a three day period failed to significantly affect granulocyte recruitment or the severity of tissue injury. In contrast, lidocaine enemas were effective in reducing both indices of inflammation/injury. In the guinea pig, similar observations were made. These observations demonstrate that blockade of NK-1 receptors over a three day period failed to significantly modify the course of experimental colitis. It remains possible that the beneficial ef...Continue Reading

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Citations

Aug 7, 2001·British Journal of Pharmacology·L de GaravillaN W Bunnett
May 27, 2010·World Journal of Gastroenterology : WJG·Ugur DumanTuncay Yilmazlar
Aug 28, 2007·Pharmacology & Therapeutics·Anneke RijnierseAletta D Kraneveld
May 19, 2007·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·E S KimballP J Hornby
Apr 18, 2008·European Journal of Pharmacology·Aletta D KraneveldJohan Garssen
Oct 21, 1999·The Journal of Pharmacy and Pharmacology·J GoldhillN Selve
Dec 17, 2004·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·E S KimballP J Hornby
Nov 30, 2000·American Journal of Physiology. Gastrointestinal and Liver Physiology·A F StucchiJ M Becker
Jul 18, 2000·American Journal of Physiology. Gastrointestinal and Liver Physiology·M J MillerM Sandoval

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