title: Acetylcholine-related bowel dysmotility in homozygous mutant NCX/HOX11L.1-deficient (NCX-/-) mice-evidence that acetylcholine is implicated in causing intestinal neuronal dysplasia.
abstract: OBJECTIVE
  Homozygous mutant Ncx/Hox11L.1-deficient (Ncx-/-) mice develop mega-ileo-ceco-colon (mega-ICC) with a caliber change in the proximal colon. The authors investigated the mechanism of intestinal dysmotility in these mice.
  
  
  METHODS
  Five-week-old Ncx-/- mice with mega ICC were compared with age-matched BDF1 control mice. Jejunum, ileum, and colon were excised from all mice and 1.0-cm-long strips of each organ, each with a resting tension of 0.5g, were suspended in an organ bath filled with Tyrode's solution at 37 degrees C and bubbled with a mixture of 95% oxygen and 5% carbon dioxide. Contractile responses to acetylcholine chloride (ACh), histamine, serotonin, and barium chloride (BaCl2) were recorded isometrically.
  
  
  RESULTS
  For ACh, Ncx-/- mice had decreased distal colon circular muscle contraction only at lower doses and decreased distal colon longitudinal muscle contraction for all doses compared with controls (P <.05 or P <.01). In the proximal colon, Ncx-/- mice had increased circular muscle contraction only at higher doses and decreased longitudinal muscle contraction only at lower doses compared with controls (P <.01 or P <.05). ACh did not affect jejunum, and there were no significant effects on ileum. There was no response to histamine and serotonin by any part of the bowel, and the response to BaCl2 was the same for both Ncx-/- mice and controls.
  
  
  CONCLUSIONS
  Only ACh differentially affected muscle contraction in Ncx-/- mice in the proximal and distal colon. Thus, ACh is implicated in causing the bowel dysmotility seen in Ncx-/- mice and human IND.
authors.affiliation: Department of Pediatric Surgery, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Yanai
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Atsuyuki
authors.initials: A
authors.lastname: Yamataka
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Lane
authors.forename: Takeshi
authors.initials: T
authors.lastname: Miyano
authors.forename: Terumasa
authors.initials: T
authors.lastname: Hayakawa
authors.forename: Kazuko
authors.initials: K
authors.lastname: Satoh
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kase
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hatano
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D017609:Barium Compounds / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D003106:Colon / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005725:Ganglia, Autonomic / Q000002:abnormalities / Q000473:pathology; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D005801:Genes, Homeobox; D006627:Hirschsprung Disease / Q000209:etiology* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D006632:Histamine / Q000494:pharmacology; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D007077:Ileal Diseases / Q000151:congenital / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D007082:Ileum / Q000187:drug effects; D007583:Jejunum / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000503:physiopathology; D009474:Neurons / Q000473:pathology*; D012701:Serotonin / Q000494:pharmacology; D013368:Submucous Plexus / Q000002:abnormalities* / Q000473:pathology
chemical_list: D017609:Barium Compounds; D002712:Chlorides; D018398:Homeodomain Proteins; C107836:Tlx2 protein, mouse; C024986:barium chloride; D012701:Serotonin; D006632:Histamine; D000109:Acetylcholine