Premium
Transient receptor potential ankyrin 1 agonists improve intestinal transit in a murine model of postoperative ileus
Author(s) -
Tsuchiya K.,
Kubota K.,
Ohbuchi K.,
Kaneko A.,
Ohno N.,
Mase A.,
Matsushima H.,
Yamamoto M.,
Miyano K.,
Uezono Y.,
Kono T.
Publication year - 2016
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.12877
Subject(s) - transient receptor potential channel , motility , chemistry , pharmacology , medicine , biology , receptor , biochemistry , microbiology and biotechnology
Background Stimulation of transient receptor potential ankyrin 1 ( TRPA 1), 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 TRPA 1 in the epithelial cells of the small intestine ( SI ). Methods The effects of various TRPA 1 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 TRPA 1 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 TRPA 1‐deficient mice. SI segments show periodic peristaltic motor activity whose periodicity disappeared in TRPA 1‐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 TRPA 1‐deficient mice. 6S and GS induced a release of 5‐ HT from RIN ‐14B cells in a dose‐ and TRPA 1‐dependent manner. Conclusions & Inferences Intraluminal TRPA 1 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 TRPA 1 on motility.