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Cited by 38Gastrointestinal motility and disordersIon Channels and ReceptorsNeuropeptides and Animal Physiology

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

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Tsuchiya, K., Kubota, K., Ohbuchi, K., Kaneko, A., Ohno, N., Mase, A., Matsushima, H., Yamamoto, M. +3 more·2016·Neurogastroenterology & Motility
DOI 10.1111/nmo.12877
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Abstract

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.

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  1. Story GM, Peier AM, Reeve AJ, Eid SR, Mosbacher J, Hricik TR, Earley TJ, Hergarden AC et al. ANKTM1, a TRP-like channel expressed in noci- ceptive neurons, is activated by cold temperatures. Cell 2003; 112: 819-29.
  2. Julius D. TRP channels and pain. Annu Rev Cell Dev Biol 2013; 29: 355-84.
  3. Holzer P. Transient receptor potential (TRP) channels as drug targets for diseases of the digestive system. Phar- macol Ther 2011; 131: 142-70.
  4. Cattaruzza F, Spreadbury I, Miranda- Morales M, Grady EF, Vanner S, Bun- nett NW. Transient receptor potential ankyrin-1 has a major role in mediat- ing visceral pain in mice. Am J Phys- iol Gastrointest Liver Physiol 2010; 298: G81-91.
  5. Mitrovic M, Shahbazian A, Bock E, Pabst MA, Holzer P. Chemo-nocicep- tive signalling from the colon is enhanced by mild colitis and blocked by inhibition of transient receptor potential ankyrin 1 channels. Br J Pharmacol 2010; 160: 1430-42.
  6. Vermeulen W, De Man JG, De Schep- per HU, Bult H, Moreels TG, Pelck- mans PA, De Winter BY. Role of TRPV1 and TRPA1 in visceral hyper- sensitivity to colorectal distension during experimental colitis in rats. Eur J Pharmacol 2013; 698: 404-12.
  7. Yang J, Li Y, Zuo X, Zhen Y, Yu Y, Gao L. Transient receptor potential ankyrin- 1 participates in visceral hyperalgesia following experimental colitis. Neu- rosci Lett 2008; 440: 237-41.
  8. Christianson JA, Bielefeldt K, Malin SA, Davis BM. Neonatal colon insult alters growth factor expression and TRPA1 responses in adult mice. Pain 2010; 151: 540-9.
  9. Engel MA, Leffler A, Niedermirtl F, Babes A, Zimmermann K, Filipovi c MR, Izydorczyk I, Eberhardt M et al. TRPA1 and substance P mediate col- itis in mice. Gastroenterology 2011; 141: 1346-58.
  10. Kimball ES, Prouty SP, Pavlick KP, Wallace NH, Schneider CR, Hornby PJ. Stimulation of neuronal receptors, neuropeptides and cytokines during experimental oil of mustard colitis. Neurogastroenterol Motil 2007; 19: 390-400.
  11. Li C, Zhu Y, Shenoy M, Pai R, Liu L, Pasricha PJ. Anatomical and func- tional characterization of a duodeno- pancreatic neural reflex that can induce acute pancreatitis. Am J Phys- iol Gastrointest Liver Physiol 2013; 304: G490-500.
  12. Kono T, Kaneko A, Omiya Y, Ohbu- chi K, Ohno N, Yamamoto M. Epithelial transient receptor potential ankyrin 1 (TRPA1)-dependent adre- nomedullin upregulates blood flow in rat small intestine. Am J Physiol Gastrointest Liver Physiol 2013; 304: G428-36.
  13. Kaji I, Karaki S, Kuwahara A. Effects of luminal thymol on epithelial trans- port in human and rat colon. Am J Physiol Gastrointest Liver Physiol 2011; 300: G1132-43.
  14. Kaji I, Yasuoka Y, Karaki S, Kuwahara A. Activation of TRPA1 by luminal stimuli induces EP4-mediated anion secretion in human and rat colon. Am J Physiol Gastrointest Liver Physiol 2012; 302: G690-701.
  15. Poole DP, Pelayo JC, Cattaruzza F, Kuo YM, Gai G, Chiu JV, Bron R, Furness JB et al. Transient receptor potential ankyrin 1 is expressed by inhibitory motoneurons of the mouse intestine. Gastroenterology 2011; 141: 565-75, 575 e561-564.
  16. Kono T, Kanematsu T, Kitajima M. Exodus of Kampo, traditional Japanese medicine, from the comple- mentary and alternative medicines: is it time yet? Surgery 2009; 146: 837- 40.
  17. Manabe N, Camilleri M, Rao A, Wong BS, Burton D, Busciglio I, Zinsmeister AR, Haruma K. Effect of daikenchuto (TU-100) on gastroin- testinal and colonic transit in humans. Am J Physiol Gastrointest Liver Physiol 2010; 298: G970-5.
  18. Shimada M, Morine Y, Nagano H, Hatano E, Kaiho T, Miyazaki M, Kono T, Kamiyama T et al. Effect of TU-100, a traditional Japanese medi- cine, administered after hepatic resec- tion in patients with liver cancer: a multi-center, phase III trial (JFMC40- 1001). Int J Clin Oncol 2015; 20: 95- 104.
  19. Akamaru Y, Takahashi T, Nishida T, Omori T, Nishikawa K, Mikata S, Yamamura N, Miyazaki S et al. Effects of daikenchuto, a Japanese herb, on intestinal motility after total gastrectomy: a prospective random- ized trial. J Gastrointest Surg 2015; 19: 467-72.
  20. Katsuno H, Maeda K, Kaiho T, Kunieda K, Funahashi K, Sakamoto J, Kono T, Hasegawa H et al. Clinical efficacy of Daikenchuto for gastroin- testinal dysfunction following colon surgery: a randomized, double-blind, multicenter, placebo-controlled study (JFMC39-0902). Jpn J Clin Oncol 2015; 45: 650-6.
  21. Satoh K, Hayakawa T, Kase Y, Ishige A, Sasaki H, Nishikawa S, Kurosawa S, Yakabi K et al. Mechanisms for contractile effect of Dai-kenchu-to in isolated guinea pig ileum. Dig Dis Sci 2001; 46: 250-6.
  22. Tokita Y, Yuzurihara M, Sakaguchi M, Satoh K, Kase Y. The pharmaco- logical effects of Daikenchuto, a tra- ditional herbal medicine, on delayed gastrointestinal transit in rat postop- erative ileus. J Pharmacol Sci 2007; 104: 303-10.
  23. de Backer O, Blanckaert B, Leybaert L, Lefebvre RA. A novel method for the evaluation of intestinal transit and contractility in mice using fluo- rescence imaging and spatiotemporal motility mapping. Neurogastroen- terol Motil 2008; 20: 700-7.
  24. Paolillo M, Preda S, Corona GL, Schinelli S. Measurement of 5-hydro- xytryptamine and 5-hydroxyindolea- cetic acid in cultured rat mesencephalic neurons by high-per- formance liquid chromatography with electrochemical detection. J Chromatogr 1993; 613: 231-7.
  25. Kikuchi D, Shibata C, Imoto H, Naitoh T, Miura K, Unno M. Intra- gastric Dai-Kenchu-To, a Japanese herbal medicine, stimulates colonic motility via transient receptor poten- tial cation channel subfamily V mem- ber 1 in dogs. Tohoku J Exp Med 2013; 230: 197-204.
  26. Tokita Y, Yamamoto M, Satoh K, Nishiyama M, Iizuka S, Imamura S, Kase Y. Possible involvement of the transient receptor potential vanilloid type 1 channel in postoperative adhe- sive obstruction and its prevention by a kampo (traditional Japanese) medi- cine, daikenchuto. J Pharmacol Sci 2011; 115: 75-83.
  27. Satoh K, Hashimoto K, Hayakawa T, Ishige A, Sasaki H, Nishikawa S, Kurosawa S, Yakabi K et al. Mecha- nism of atropine-resistant contrac- tion induced by Dai-kenchu-to in guinea pig ileum. Jpn J Pharmacol 2001; 86: 32-7.
  28. Kono T, Kaneko A, Hira Y, Suzuki T, Chisato N, Ohtake N, Miura N, Watanabe T. Anti-colitis and -adhe- sion effects of daikenchuto via endogenous adrenomedullin enhancement in Crohn's disease mouse model. J Crohns Colitis 2010; 4: 161-70.
  29. De Winter BY, Boeckxstaens GE, De Man JG, Moreels TG, Herman AG, Pelckmans PA. Effect of adrenergic and nitrergic blockade on experimen- tal ileus in rats. Br J Pharmacol 1997; 120: 464-8.
  30. Lubbers T, Buurman W, Luyer M. Controlling postoperative ileus by vagal activation. World J Gastroen- terol 2010; 16: 1683-7.
  31. de Jonge WJ, The FO, van der Coelen D,Bennink RJ, Reitsma PH, vanDeventer SJ, vanden Wijngaard RM, Boeckxstaens GE. Mast cell degranulation during abdominal sur- gery initiates postoperative ileus in mice. Gastroenterology 2004; 127: 535-45.
  32. de Jonge WJ, van den Wijngaard RM, The FO, ter Beek ML, Bennink RJ, Tytgat GN, Buijs RM, Reitsma PH et al. Postoperative ileus is main- tained by intestinal immune infil- trates that activate inhibitory neural pathways in mice. Gastroenterology 2003; 125: 1137-47.
  33. Kalff JC, Carlos TM, Schraut WH, Billiar TR, Simmons RL, Bauer AJ. Surgically induced leukocytic infiltrates within the rat intestinal muscularis mediate postoperative ileus. Gastroenterology 1999; 117: 378-87.
  34. Schwarz NT, Kalff JC, Turler A, Engel BM, Watkins SC, Billiar TR, Bauer AJ. Prostanoid production via COX-2 as a causative mechanism of rodent post- operative ileus. Gastroenterology 2001; 121: 1354-71.
  35. van Bree SH, Nemethova A, van Bovenkamp FS, Gomez-Pinilla P, Elbers L, Di Giovangiulio M, Matteoli G, vanVliet J et al. Novel method for studying postoperative ileus in mice. Int J Physiol Pathophysiol Pharmacol 2012; 4: 219-27.
  36. Wehner S, Behrendt FF, Lyutenski BN, Lysson M, Bauer AJ, Hirner A, Kalff JC. Inhibition of macrophage function prevents intestinal inflam- mation and postoperative ileus in rodents. Gut 2007; 56: 176-85.
  37. Schmidt J, Stoffels B, Nazir A, Deha- ven-Hudkins DL, Bauer AJ. Alvi- mopan and COX-2 inhibition reverse opioid and inflammatory components of postoperative ileus. Neurogas- troenterol Motil 2008; 20: 689-99.
  38. Stoffels B, Schmidt J, Nakao A, Nazir A, Chanthaphavong RS, Bauer AJ. Role of interleukin 10 in murine postoperative ileus. Gut 2009; 58: 648-60.
  39. The FO, de Jonge WJ, Bennink RJ, van den Wijngaard RM, Boeckxstaens GE. The ICAM-1 antisense oligonu- cleotide ISIS-3082 prevents the devel- opment of postoperative ileus in mice. Br J Pharmacol 2005; 146: 252-8.
  40. Liu X, Wu T, Chi P. Inhibition of MK2 shows promise for preventing postoperative ileus in mice. J Surg Res 2013; 185: 102-12.
  41. van Bree SH, Gomez-Pinilla PJ, van de Bovenkamp FS, Di Giovangiulio M, Farro G, Nemethova A, Cailotto C, deJonge WJ et al. Inhibition of spleen tyrosine kinase as treatment of postoperative ileus. Gut 2013; 62: 1581-90.
  42. Wehner S, Straesser S, Vilz TO, Pan- telis D, Sielecki T, dela Cruz VF, Hirner A, Kalff JC. Inhibition of p38 mitogen-activated protein kinase pathway as prophylaxis of postopera- tive ileus in mice. Gastroenterology 2009; 136: 619-29.
  43. Moore BA, Manthey CL, Johnson DL, Bauer AJ. Matrix metallopro- teinase-9 inhibition reduces inflam- mation and improves motility in murine models of postoperative ileus. Gastroenterology 2011; 141: 1283-92, 1292 e1281-1284.
  44. De Backer O, Elinck E, Blanckaert B, Leybaert L, Motterlini R, Lefebvre RA. Water-soluble CO-releasing molecules reduce the development of postoperative ileus via modulation of MAPK/HO-1 signalling and reduc- tion of oxidative stress. Gut 2009; 58: 347-56.
  45. Moore BA, Otterbein LE, Turler A, Choi AM, Bauer AJ. Inhaled carbon monoxide suppresses the develop- ment of postoperative ileus in the murine small intestine. Gastroen- terology 2003; 124: 377-91.
  46. The FO, Boeckxstaens GE, Snoek SA, Cash JL, Bennink R, Larosa GJ, vanden Wijngaard RM, Greaves DR et al. Activation of the cholinergic anti-inflammatory pathway amelio- rates postoperative ileus in mice. Gastroenterology 2007; 133: 1219-28.
  47. Endo M, Hori M, Ozaki H, Oikawa T, Hanawa T. Rikkunshito, a Kampo medicine, ameliorates post-operative ileus by anti-inflammatory action. J Pharmacol Sci 2014; 124: 374-85.
  48. Lubbers T, Luyer MD, de Haan JJ, Hadfoune M, Buurman WA, Greve JW. Lipid-rich enteral nutrition reduces postoperative ileus in rats via activation of cholecystokinin- receptors. Ann Surg 2009; 249: 481-7.
  49. Stoffels B, Turler A, Schmidt J, Nazir A, Tsukamoto T, Moore BA, Schnurr C, Kalff JC et al. Anti-inflammatory role of glycine in reducing rodent postoperative inflammatory ileus. Neurogastroenterol Motil 2011; 23: 76-87, e78.
  50. Tan S, Yu W, Lin Z, Chen Q, Shi J, Dong Y, Duan K, Bai X et al. Anti- inflammatory effect of ginsenoside Rb1 contributes to the recovery of gastrointestinal motility in the rat model of postoperative ileus. Biol Pharm Bull 2014; 37: 1788-94.
  51. Wehner S, Meder K, Vilz TO, Alte- held B, Stehle P, Pech T, Kalff JC. Preoperative short-term parenteral administration of polyunsaturated fatty acids ameliorates intestinal inflammation and postoperative ileus in rodents. Langenbecks Arch Surg 2012; 397: 307-15.
  52. Zhang B, Cao A, Zhou J, Hu Z, Wu D. Effect of jatrorrhizine on delayed gas- trointestinal transit in rat postopera- tive ileus. J Pharm Pharmacol 2012; 64: 413-9.
  53. Bartho L, Nordtveit E, Szombati V, Benko R. Purinoceptor-mediated, capsaicin-resistant excitatory effect of allyl isothiocyanate on neurons of the guinea-pig small intestine. Basic Clin Pharmacol Toxicol 2013; 113: 141-3.
  54. Capasso R, Aviello G, Romano B, Borrelli F, De Petrocellis L, Di Marzo V, Izzo AA. Modulation of mouse gastrointestinal motility by allyl isothiocyanate, a constituent of cru- ciferous vegetables (Brassicaceae): evidence for TRPA1-independent effects. Br J Pharmacol 2012; 165: 1966-77.
  55. Penuelas A, Tashima K, Tsuchiya S, Matsumoto K, Nakamura T, Horie S, Yano S. Contractile effect of TRPA1 receptor agonists in the isolated mouse intestine. Eur J Pharmacol 2007; 576: 143-50.
  56. Doihara H, Nozawa K, Kawabata- Shoda E, Kojima R, Yokoyama T, Ito H. Molecular cloning and character- ization of dog TRPA1 and AITC stimulate the gastrointestinal motil- ity through TRPA1 in conscious dogs. Eur J Pharmacol 2009; 617: 124-9.
  57. Kim MJ, Son HJ, Song SH, Jung M, Kim Y, Rhyu MR. The TRPA1 ago- nist, methyl syringate suppresses food intake and gastric emptying. PLoS ONE 2013; 8: e71603.
  58. Doihara H, Nozawa K, Kawabata- Shoda E, Kojima R, Yokoyama T, Ito H. TRPA1 agonists delay gastric emp- tying in rats through serotonergic pathways. Naunyn Schmiedebergs Arch Pharmacol 2009; 380: 353-7.
  59. Kojima R, Nozawa K, Doihara H, Keto Y, Kaku H, Yokoyama T, Itou H. Effects of novel TRPA1 receptor agonist ASP7663 in models of drug- induced constipation and visceral pain. Eur J Pharmacol 2014; 723: 288-93.
  60. Someya S, Nagao M, Shibata C, Tanaka N, Sasaki H, Kikuchi D, Miyachi T, Naitoh T et al. Intra- colonic administration of the TRPA1 agonist allyl isothiocyanate stimu- lates colonic motility and defecation in conscious dogs. J Gastrointest Surg 2015; 19: 1342-9.
  61. Cho HJ, Callaghan B, Bron R, Bravo DM, Furness JB. Identification of enteroendocrine cells that express TRPA1 channels in the mouse intes- tine. Cell Tissue Res 2014; 356: 77-82.
  62. Zhang Y. Allyl isothiocyanate as a cancer chemopreventive phytochem- ical. Mol Nutr Food Res 2010; 54: 127-35.
  63. Antipenko AY, Spielman AI, Kirch- berger MA. Interactions of 6-gingerol and ellagic acid with the cardiac sarcoplasmic reticulum Ca 2+ -ATPase. J Pharmacol Exp Ther 1999; 290: 227- 34.
  64. Bautista DM, Sigal YM, Milstein AD, Garrison JL, Zorn JA, Tsuruda PR, Nicoll RA, Julius D. Pungent agents from Szechuan peppers excite sensory neurons by inhibiting two-pore potas- sium channels. Nat Neurosci 2008; 11: 772-9.
  65. Dossou KS, Devkota KP, Morton C, Egan JM, Lu G, Beutler JA, Moaddel R. Identification of CB1/CB2 ligands from Zanthoxylum bungeanum. J Nat Prod 2013; 76: 2060-4.
  66. Nievergelt A, Marazzi J, Schoop R, Altmann KH, Gertsch J. Ginger phenylpropanoids inhibit IL-1beta and prostanoid secretion and disrupt arachidonate-phospholipid remodel- ing by targeting phospholipases A2. J Immunol 2011; 187: 4140-50.
  67. Riera CE, Menozzi-Smarrito C, Affolter M, Michlig S, Munari C, Robert F, Vogel H, Simon SA et al. Compounds from Sichuan and Mele- gueta peppers activate, covalently and non-covalently, TRPA1 and TRPV1 channels. Br J Pharmacol 2009; 157: 1398-409.
  68. Ueno N, Hasebe T, Kaneko A, Yama- moto M, Fujiya M, Kohgo Y, Kono T, Wang CZ et al. TU-100 (Daikench- uto) and ginger ameliorate anti-CD3 antibody induced T cell-mediated murine enteritis: microbe-indepen- dent effects involving Akt and NF- kappaB suppression. PLoS ONE 2014; 9: e97456.
  69. Kubota K, Ohtake N, Ohbuchi K, Mase A, Imamura S, Sudo Y, Miyano K, Yamamoto M et al. Hydroxy-alpha- sanshool induces colonic motor activ- ity in rat proximal colon: a possible involvement of KCNK9. Am J Physiol Gastrointest Liver Physiol 2015; 308: G579-90.
  70. Iwabu J, Watanabe J, Hirakura K, Ozaki Y, Hanazaki K. Profiling of the compounds absorbed in human plasma and urine after oral adminis- tration of a traditional Japanese (kampo) medicine, daikenchuto. Drug Metab Dispos 2010; 38: 2040-8.

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Authors
Tsuchiya, K., Kubota, K., Ohbuchi, K., Kaneko, A., Ohno, N., Mase, A., Matsushima, H., Yamamoto, M., Miyano, K., Uezono, Y., & Kono, T.
Affiliations
  • Tsumura Research Institute (Japan) (JP)
  • National Cancer Center Research Institute (JP)
  • Hokkaido University (JP)
Corresponding author
Kono, T.
ORCID
Venue
Neurogastroenterology & Motility
Publisher
Wiley
Published
2016-06-10
Volume
28
Issue
12
Pages
1792-1805
ISSN
  • 1350-1925 (ISSN-L)
  • 1365-2982
DOI
10.1111/nmo.12877
OpenAlex
W2417808178
Cited by
38
References
1
Citations by year
2026: 4 · 2025: 2 · 2024: 3 · 2023: 5 · 2022: 6 · 2021: 3 · 2020: 4 · 2019: 4 · 2018: 4 · 2017: 3
FWCI
4.01
Type
journal article
Language
en
Open access
Licence
Locations
  • Neurogastroenterology & Motility (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
Hokkaido University
Topics
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
  • Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords
TRPA1 agonists, postoperative ileus, intestinal transit, Daikenchuto, cinnamaldehyde, 6-shogaol, enterochromaffin cells, serotonin release, small intestine motility, peristalsis, gastrointestinal motility disorders
MeSH terms
TRPA1 Cation Channel, Acrolein, Amides, Animals, Cells, Cultured, Disease Models, Animal, Dose-Response Relationship, Drug, Gastrointestinal Transit, Male, Mice, Inbred C57BL, Naphthoquinones, Organ Culture Techniques, Ileus, Mice, Mice, 129 Strain

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