title: Non-neuronal, but atropine-sensitive ileal contractile responses to short-chain fatty acids: age-dependent desensitization and restoration under inflammatory conditions in mice.
abstract: Intestinal epithelial cells sense short-chain fatty acids (SCFAs) to secrete non-neuronal acetylcholine (ACh). However, the roles of luminalSCFAs and epithelialACh under normal and pathological conditions remain unknown. We examined ileal contractile responses toSCFAs at different ages and their mucosal cholinergic alterations under inflammatory conditions. Ileal contractile responses toSCFAs in 1-day-old pups to 7-week-old mice were compared using an isotonic transducer, and responses to an intraperitoneal injection of lipopolysaccharide (LPS) were analyzed in 7-week-old mice. ThemRNAexpression levels of aSCFAactivate free fatty acid receptor, acetylcholinesterase (AChE), choline acetyltransferase (Chat), and choline transporter-like protein 4 (CTL4) were measured using real-time quantitativeRT-PCRAChE was analyzed by histochemical and optical enzymatic assays. Atropine-sensitive ileal contractile responses toSCFAs occurred in all 1-day-old pups, but were frequently desensitized after the weaning period. These contractile responses were not inhibited by tetrodotoxin and did not appear when the mucosal layer had been scraped off. Contractile desensitization in 7-week-old mice was abolished in the presence of theAChE inhibitor, eserine, which was consistent with increasedAChE activity after weaning. Ileal contractions toSCFAs in adult mice were restored byLPS, which significantly increased the epithelialmRNAexpression of Chat andCTL4. Atropine-sensitive ileal contractile responses toSCFAs constitutively occur in the newborn period, and are desensitized during developmental stages following the up-regulated expression ofAChE in the villous mucosa, but are restored under inflammatory conditions possibly via the release of epithelialACh.
authors.affiliation: Laboratory of Histology and Cytology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan Laboratory of Physiology, School of Food and Nutritional Sciences, Graduate Division of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka, Japan Meiji Dairies Research Chair, Creative Research Institution, Hokkaido University, Sapporo, Japan yajimama@cris.hokudai.ac.jp.
authors.forename: Masako
authors.initials: M
authors.lastname: Yajima
authors.affiliation: Laboratory of Histology and Cytology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kimura
authors.affiliation: Laboratory of Physiology, School of Food and Nutritional Sciences, Graduate Division of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Karaki
authors.affiliation: Laboratory of Histology and Cytology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Nio-Kobayashi
authors.affiliation: Meiji Dairies Research Chair, Creative Research Institution, Hokkaido University, Sapporo, Japan Department of Animal Science, Graduate School of Natural Science and Technology, Okayama University, Okayama, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tsuruta
authors.affiliation: Laboratory of Physiology, School of Food and Nutritional Sciences, Graduate Division of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Atsukazu
authors.initials: A
authors.lastname: Kuwahara
authors.affiliation: Laboratory of Histology and Cytology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan Meiji Dairies Research Chair, Creative Research Institution, Hokkaido University, Sapporo, Japan.
authors.forename: Takaji
authors.initials: T
authors.lastname: Yajima
authors.affiliation: Laboratory of Histology and Cytology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Iwanaga
mesh_terms: D019342:Acetic Acid / Q000494:pharmacology; D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000235:genetics / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D002795:Choline O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005227:Fatty Acids / Q000494:pharmacology*; D058851:GPI-Linked Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D008807:Mice, Inbred BALB C; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D011422:Propionates / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: D002800:Cholinesterase Inhibitors; D005227:Fatty Acids; C506481:Ffar2 protein, mouse; D058851:GPI-Linked Proteins; D008070:Lipopolysaccharides; D026901:Membrane Transport Proteins; D011422:Propionates; D043562:Receptors, G-Protein-Coupled; C482199:lipopolysaccharide, E coli O55-B5; D001285:Atropine; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; C548245:Ache protein, mouse; C029658:propionic acid; D000109:Acetylcholine; D019342:Acetic Acid
keywords: Acetylcholinesterase; age; ileal contraction; inflammatory condition; non‐neuronal acetylcholine; short‐chain fatty acids