title: Carbachol ameliorates lipopolysaccharide-induced intestinal epithelial tight junction damage by down-regulating NF-κβ and myosin light-chain kinase pathways.
abstract: Carbachol is a cholinergic agonist that protects the intestines after trauma or burn injury. The present study determines the beneficial effects of carbachol and the mechanisms by which it ameliorates the lipopolysaccharide (LPS)-induced intestinal barrier breakdown. Rats were injected intraperitoneally with 10 mg/kg LPS. Results showed that the gut barrier permeability was reduced, the ultrastructural disruption of tight junctions (TJs) was prevented, the redistribution of zonula occludens-1 and claudin-2 proteins was partially reversed, and the nuclear factor-kappa beta (NF-κβ) and myosin light-chain kinase (MLCK) activation in the intestinal epithelium were suppressed after carbachol administration in LPS-exposed rats. Pretreatment with the α7 nicotinic acetylcholine receptor (α7nAchR) antagonist α-bungarotoxin blocked the protective action of carbachol. These results suggested that carbachol treatment can protect LPS-induced intestinal barrier dysfunction. Carbachol exerts its beneficial effect on the amelioration of the TJ damage by inhibiting the NF-κβ and MLCK pathways in an α7nAchR-dependent manner.
authors.affiliation: Department of Anesthesia, Critical Care Medicine & Emergency Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jianguo
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D018679:Cholinergic Agonists / Q000494:pharmacology*; D019610:Cytoprotection; D015536:Down-Regulation; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors*; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D019108:Tight Junctions / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D018679:Cholinergic Agonists; D008070:Lipopolysaccharides; D016328:NF-kappa B; D002217:Carbachol; D009219:Myosin-Light-Chain Kinase