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Involvement of CPI-17 downregulation in the dysmotility of the colon from dextran sodium sulphate-induced experimental colitis in a mouse model
- Source :
- Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. 19(6)
- Publication Year :
- 2007
-
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.
- Subjects :
- medicine.medical_specialty
RHOA
Physiology
Blotting, Western
GTPgammaS
Down-Regulation
Muscle Proteins
Cholinergic Agonists
Inflammatory bowel disease
chemistry.chemical_compound
Mice
Downregulation and upregulation
Internal medicine
Myosin
Medicine
Animals
Colitis
Enzyme Inhibitors
Gastrointestinal dysmotility
Receptor, Muscarinic M3
Mice, Inbred BALB C
biology
Endocrine and Autonomic Systems
business.industry
Reverse Transcriptase Polymerase Chain Reaction
Dextran Sulfate
Gastroenterology
Intracellular Signaling Peptides and Proteins
Anticoagulants
Muscle, Smooth
medicine.disease
Phosphoproteins
Ulcerative colitis
digestive system diseases
Disease Models, Animal
Endocrinology
chemistry
Immunology
biology.protein
Carbachol
Female
business
Gastrointestinal Motility
Muscle Contraction
Subjects
Details
- ISSN :
- 13501925
- Volume :
- 19
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society
- Accession number :
- edsair.doi.dedup.....a51fd869f9a4e3a1b135c0c85972d16a