title: Involvement of CPI-17 downregulation in the dysmotility of the colon from dextran sodium sulphate-induced experimental colitis in a mouse model.
abstract: The mechanism of gastrointestinal dysmotility in inflammatory bowel disease has not been clarified. In this study, we examined the mechanism involved in the inflamed distal colon isolated from a mouse model of dextran sodium sulphate-induced ulcerative colitis (DSS-treated mouse). Although substance P-induced contraction was not changed, carbachol-induced contraction was reduced in the DSS-treated mouse colon. Pre-incubation with the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA) or the cyclooxygenase inhibitor indomethacin did not reverse the carbachol-induced contraction in the DSS-treated mouse colon. In semi-quantitative reverse transcription-polymerase chain reaction experiments and Western blot analysis, muscarinic M3 receptor expressions were not changed. The Ca2+ -sensitization of contractile elements induced by carbachol with GTP or GTPgammaS was reduced in the beta-escin-permeabilized DSS-treated mouse colon. Although the expression of proteins such as rhoA, ROCK1, ROCK2 or MYPT1 in smooth muscles was not changed, the expression of CPI-17, the functional protein involved in smooth muscle Ca2+ -sensitization, was significantly decreased in the DSS-treated mouse colon. These results suggest that the suppression of carbachol-induced contraction in mice with colitis is attributable at least partially to the increased activity of myosin phosphatase following the downregulation of CPI-17.
authors.affiliation: Department of Veterinary Pharmacology, Faculty of Agriculture, Yamaguchi University, Yamaguchi, Japan. k-sato@yamaguchi-u.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Sato
authors.forename: S
authors.initials: S
authors.lastname: Ohkura
authors.forename: Y
authors.initials: Y
authors.lastname: Kitahara
authors.forename: T
authors.initials: T
authors.lastname: Ohama
authors.forename: M
authors.initials: M
authors.lastname: Hori
authors.forename: M
authors.initials: M
authors.lastname: Sato
authors.forename: S
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Sasaki
authors.forename: T
authors.initials: T
authors.lastname: Hayashi
authors.forename: T
authors.initials: T
authors.lastname: Nasu
authors.forename: H
authors.initials: H
authors.lastname: Ozaki
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000633:toxicity; D015153:Blotting, Western; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009124:Muscle Proteins / Q000187:drug effects / Q000378:metabolism*; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D010750:Phosphoproteins / Q000187:drug effects / Q000378:metabolism*; D043587:Receptor, Muscarinic M3 / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000925:Anticoagulants; D018679:Cholinergic Agonists; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D010750:Phosphoproteins; C491520:Ppp1r14a protein, mouse; D043587:Receptor, Muscarinic M3; D002217:Carbachol; D016264:Dextran Sulfate