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Transient receptor potential ankyrin 1 agonists improve intestinal transit in a murine model of postoperative ileus.

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  • معلومة اضافية
    • المصدر:
      Publisher: Blackwell Scientific Publications Country of Publication: England NLM ID: 9432572 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2982 (Electronic) Linking ISSN: 13501925 NLM ISO Abbreviation: Neurogastroenterol Motil Subsets: MEDLINE
    • بيانات النشر:
      Original Publication: Osney Mead, Oxford, UK : Blackwell Scientific Publications, c1994-
    • الموضوع:
      Disease Models, Animal*; Gastrointestinal Transit/*drug effects ; Gastrointestinal Transit/*physiology ; Ileus/*drug therapy ; TRPA1 Cation Channel/*agonists ; TRPA1 Cation Channel/*physiology; Acrolein/analogs & derivatives ; Acrolein/pharmacology ; Acrolein/therapeutic use ; Amides/pharmacology ; Amides/therapeutic use ; Animals ; Cells, Cultured ; Dose-Response Relationship, Drug ; Ileus/physiopathology ; Male ; Mice ; Mice, 129 Strain ; Mice, Inbred C57BL ; Naphthoquinones/pharmacology ; Naphthoquinones/therapeutic use ; Organ Culture Techniques
    • نبذة مختصرة :
      Background: Stimulation of transient receptor potential ankyrin 1 (TRPA1), which abundantly expressed in enterochromaffin cells (ECC), has been reported to exert apparently contradictory results in in vitro contractility and in vivo gastrointestinal (GI) transit evaluations. The pharmaceutical-grade Japanese traditional medicine daikenchuto (TU-100) has been reported to be beneficial for postoperative ileus (POI) and accelerate GI transit in animals and humans. TU-100 was recently shown to increase intestinal blood flow via stimulation of TRPA1 in the epithelial cells of the small intestine (SI).
      Methods: The effects of various TRPA1 agonists on motility were examined in a manipulation-induced murine POI model, in vitro culture of SI segments and an ECC model cell line, RIN-14B.
      Key Results: Orally administered TRPA1 agonists, aryl isothiocyanate (AITC) and cinnamaldehyde (CA), TU-100 ingredients, [6]-shogaol (6S) and γ-sanshool (GS), improved SI transit in a POI model. The effects of AITC, 6S and GS but not CA were abrogated in TRPA1-deficient mice. SI segments show periodic peristaltic motor activity whose periodicity disappeared in TRPA1-deficient mice. TU-100 augmented the motility. AITC, CA and 6S increased 5-HT release from isolated SI segments and the effects of all these compounds except for CA were lost in TRPA1-deficient mice. 6S and GS induced a release of 5-HT from RIN-14B cells in a dose- and TRPA1-dependent manner.
      Conclusions & Inferences: Intraluminal TRPA1 stimulation is a potential therapeutic strategy for GI motility disorders. Further investigation is required to determine whether 5-HT and/or ECC are involved in the effect of TRPA1 on motility.
      (© 2016 The Authors. Neurogastroenterology & Motility Published by John Wiley & Sons Ltd.)
    • Contributed Indexing:
      Keywords: aryl isothiocyanate; daikenchuto; enterochromaffin cells; shogaol; γ-sanshool
    • الرقم المعرف:
      0 (12,13-dihydro-N-methyl-6,11,13-trioxo-5H-benzo(4,5)cyclohepta(1,2-b)naphthalen-5,12-imine)
      0 (Amides)
      0 (Naphthoquinones)
      0 (TRPA1 Cation Channel)
      0 (Trpa1 protein, mouse)
      504-97-2 (sanshool)
      7864XYD3JJ (Acrolein)
      SR60A3XG0F (cinnamaldehyde)
    • الموضوع:
      Date Created: 20160611 Date Completed: 20180131 Latest Revision: 20210702
    • الموضوع:
      20250114
    • الرقم المعرف:
      10.1111/nmo.12877
    • الرقم المعرف:
      27284001