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Isolated ileal or colonic segments in anesthetized rats were pretreated with nicotine bitartrate or other pharmacological agents before intraluminal injection of toxin A. After 3 hours, the treated segments were removed and inflammation was assessed. Nicotine biphasically inhibited toxin A colitis but not ileitis. Pretreatment with the nicotinic receptor antagonist, hexamethonium, blocked the effects of nicotine. Pretreating the colonic segments with hexamethonium before toxin A administration resulted in more inflammation than seen with toxin A alone, suggesting that a tonic nicotinic anti-inflammatory condition exists in the colon. Nicotine also inhibited toxin A-induced increased colonic concentrations of the TRPV1 (transient receptor potential vanilloid subtype 1) agonist, leukotriene B<jats:sub>4<\/jats:sub>(LTB<jats:sub>4<\/jats:sub>), and release of the proinflammatory neuropeptide, substance P. Pretreatment with nicotine did not protect against direct TRPV1-mediated colitis caused by intraluminal capsaicin. Nicotinic cholinergic receptors tonically protect the colon against inflammation and nicotine inhibits toxin A colitis but not toxin A ileitis in rats in part by inhibition of toxin A-induced activation of TRPV1 by endogenous TRPV1 agonists such as LTB<jats:sub>4<\/jats:sub>.<\/jats:p>","DOI":"10.1155\/2016\/4705065","type":"journal-article","created":{"date-parts":[[2016,1,11]],"date-time":"2016-01-11T16:01:55Z","timestamp":1452528115000},"page":"1-10","source":"Crossref","is-referenced-by-count":3,"title":["Nicotine Inhibits<i>Clostridium difficile<\/i>Toxin A-Induced Colitis but Not Ileitis in Rats"],"prefix":"10.1155","volume":"2016","author":[{"given":"Steven R.","family":"Vigna","sequence":"first","affiliation":[{"name":"Departments of Cell Biology & Medicine, Duke University Medical Center, Durham, NC 72210, USA"},{"name":"Durham VA Medical Center, Durham, NC 27705, 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