title: Mast cell degranulation inhibits motor patterns of human ileum and sigmoid colon in vitro: relevance for postoperative ileus.
abstract: BACKGROUND
  Local release of mast cell proteases during gastrointestinal surgery is associated with the inhibition of motility and postoperative ileus (POI). We determined whether activation of intramuscular mast cell affects the motor patterns of the human ileum and colon and whether proteases are involved.
  
  
  METHODS
  Motor response of ileal and colonic circular muscle strips was measured in organ bath. Mast cell degranulation was induced by compound 48/80 (c48/80; 25-675 μg/mL). Motor response was quantified as tone, rhythmic phasic contractions (RPCs) and contractions to electric field stimulation (EFS; 40 Hz), and bethanechol-evoked contractions. Ketotifen (10(-6) mol/L) and a protease inhibitor cocktail (P8340) were used to evaluate the role of mast cell mediators.
  
  
  RESULTS
  (a) c48/80 impaired the spontaneous and the electrically evoked motor response in small bowel and colonic strips (sigmoid colon EC50 : 460.0 μg/mL for RPCs and 8.9 μg/mL for electrically evoked contraction amplitudes) and bethanechol-evoked contractions. (b) Preincubation with ketotifen (10(-6) mol/L, 1 h) prevented the impairment of RPCs and EFS-evoked contractions in the sigmoid colon and ileum but not in the right colon. (c) Preincubation with P8340 also prevented the impairment of contractions in the sigmoid colon but not in the ileum or the right colon.
  
  
  CONCLUSIONS
  Mast cell degranulation by c48/80 inhibits the spontaneous and the nerve-mediated motor response in the human ileum and colon. The effect is partially mediated by mast cell proteases and could be relevant in the pathophysiology of POI.
authors.affiliation: CIBERehd, Centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas, Instituto de Salud Carlos III, Barcelona, Catalonia, Spain.|Department of Cell Biology, Physiology and Immunology, Veterinary School, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Rychter
authors.affiliation: Department of Surgery, Hospital de Mataró, Universitat Autónoma de Barcelona, Mataró, Catalonia, Spain.
authors.forename: O
authors.initials: O
authors.lastname: Ortega
authors.affiliation: Department of Cell Biology, Physiology and Immunology, Veterinary School, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Berdun
authors.affiliation: CIBERehd, Centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas, Instituto de Salud Carlos III, Barcelona, Catalonia, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Arenas
authors.affiliation: Department of Surgery, Hospital de Mataró, Universitat Autónoma de Barcelona, Mataró, Catalonia, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Lopez
authors.affiliation: Department of Surgery, Hospital de Mataró, Universitat Autónoma de Barcelona, Mataró, Catalonia, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Espin
authors.affiliation: CIBERehd, Centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas, Instituto de Salud Carlos III, Barcelona, Catalonia, Spain.|Department of Cell Biology, Physiology and Immunology, Veterinary School, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Vergara
authors.affiliation: CIBERehd, Centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas, Instituto de Salud Carlos III, Barcelona, Catalonia, Spain.|Department of Surgery, Hospital de Mataró, Universitat Autónoma de Barcelona, Mataró, Catalonia, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Clavé
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015550:Cell Degranulation; D012809:Colon, Sigmoid / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000502:physiology*; D045823:Ileus / Q000150:complications / Q000503:physiopathology; D066298:In Vitro Techniques; D007665:Ketotifen / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D011183:Postoperative Complications; D011480:Protease Inhibitors / Q000494:pharmacology; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology*
chemical_list: D011480:Protease Inhibitors; D003189:p-Methoxy-N-methylphenethylamine; D007665:Ketotifen
keywords: intestinal manipulation; ketotifen; mast cells; motor patterns; postoperative ileus; proteases