CC BY-NC-ND 4.0 · Planta Medica International Open 2022; 9(01): e72-e79
DOI: 10.1055/a-1712-8391
Original Papers

Daikenchuto, a Traditional Kampo Medicine, Facilitates Mucosal Hyperemic Responses through Activation of TRPA1- and TRPV1-Expressing Sensory Nerves in Rat Stomach

Masatoshi Yoshikubo
1   Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Josai International University, Togane, Chiba, Japan
,
Kimihito Tashima
1   Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Josai International University, Togane, Chiba, Japan
2   Center of Pharmacological Kampo Research, Josai International University, 1 Gumyo, Togane, Chiba, Japan
,
Masaki Raimura
1   Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Josai International University, Togane, Chiba, Japan
,
Yuto Watanabe
1   Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Josai International University, Togane, Chiba, Japan
,
Yukiko Noma
1   Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Josai International University, Togane, Chiba, Japan
,
Syunji Horie
1   Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Josai International University, Togane, Chiba, Japan
2   Center of Pharmacological Kampo Research, Josai International University, 1 Gumyo, Togane, Chiba, Japan
› Institutsangaben

Abstract

Daikenchuto is a traditional Kampo medicine used to treat cold sensations and dysmotility in the abdomen. This study investigated the roles of transient receptor potential ankyrin 1- and transient reporter potential vanilloid 1-expressing sensory nerves in daikenchuto-induced gastric mucosal blood flow by pharmacological and immunohistochemical analyses using male Sprague-Dawley rats. Gastric mucosal blood flow was measured in ex vivo stomachs using a laser Doppler flowmeter. Transient receptor potential ankyrin 1 activator allyl isothiocyanate or transient reporter potential vanilloid 1 activator capsaicin were applied for 10 min, and daikenchuto was applied for 10 or 30 min to the rat stomach. Transient reporter potential vanilloid 1 blocker N-(4-t-butylphenyl)-4-(3-chlopyridin-2-yl) tetrahydropyrazine-1(2H)-carboxamide and transient receptor potential ankyrin 1 blocker A-967079 were also administered intragastrically. Capsaicin and allyl isothiocyanate increased gastric mucosal blood flow immediately after the intragastric application, which was almost completely inhibited by N-(4-t-butylphenyl)-4-(3-chlopyridin-2-yl) tetrahydropyrazine-1(2H)-carboxamide and A-967079, respectively. Daikenchuto increased gastric mucosal blood flow in a concentration-dependent manner. A-967079 significantly inhibited the increase in gastric mucosal blood flow induced by daikenchuto. In contrast, N-(4-t-butylphenyl)-4-(3-chlopyridin-2-yl) tetrahydropyrazine-1(2H)-carboxamide inhibited the responses to daikenchuto only in the late phase but not in the initial phase. Interestingly, in the deafferentation of capsaicin-sensitive sensory fiber in rats, the increased gastric mucosal blood flow induced by daikenchuto was only decreased in the late phase. Although transient receptor potential ankyrin 1- and transient reporter potential vanilloid 1-immunoreactive fibers were observed around the submucosal blood vessels of normal subjects, they were completely absent in the deafferentation of capsaicin-sensitive sensory fibers. Thus, daikenchuto increases gastric mucosal blood flow via transient receptor potential ankyrin 1- and transient reporter potential vanilloid 1-co-expressing sensory nerves in rat stomachs.

Supplementary Material



Publikationsverlauf

Eingereicht: 10. April 2021
Eingereicht: 23. September 2021

Angenommen: 19. Oktober 2021

Artikel online veröffentlicht:
07. März 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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  • References

  • 1 Manabe N, Camilleri M, Rao A, Wong B, Burton D, Busciglio L, Zinsmeister AR, Haruma K. Effect of daikenchuto (TU-100) on human gastrointestinal and colonic transit. Am J Physiol Gastrointest Liver Physiol 2010; 298: G970-G975
  • 2 Katsuno H, Maeda K, Kaiho T, Kunieda K, Funahashi K, Sakamoto J, Kono T, Hasegawa H, Furukawa Y, Imazu Y, Morita S, Watanabe M. Clinical efficacy of Daikenchuto for gastrointestinal dysfunction following colon surgery: a randomized, double-blind, multicenter, placebo-controlled study (JFMC39-0902). Jpn J Clin Oncol 2015; 45: 650-656
  • 3 Takayama S, Seki T, Watanabe M, Monma Y, Sugita N, Konno S, Iwasaki K, Takeda T, Yambe T, Yoshizawa M, Nitta S, Yaegashi N. The herbal medicine Daikenchuto increases blood flow in the superior mesenteric artery. Tohoku J Exp Med 2009; 219: 319-330
  • 4 Kono T, Koseki T, Chiba S, Ebisawa Y, Chisato N, Iwamoto J, Kasai S. Colonic vascular conductance increased by daikenchuto via calcitonin gene-related peptide and receptor-activity modifying protein 1. J Surg Res 2008; 150: 78-84
  • 5 Satoh K, Kase Y, Hayakawa T, Murata P, Ishige A, Sasaki H. Dai-kenchu-to enhances accelerated small intestinal movement. Biol Pharm Bull 2001; 24: 1122-1126
  • 6 Kikuchi D, Shibata C, Imoto H, Naitoh T, Miura K, Unno M. Intragastric Dai-Kenchu-To, a Japanese herbal medicine, stimulates colonic motility via transient receptor potential cation channel subfamily V member 1 in dogs. Tohoku J Exp Med 2013; 230: 197-204
  • 7 Mochiki E, Yanai M, Ohno T, Kuwano H. The effect of traditional Japanese medicine (Kampo) on gastrointestinal function. Surg Today 2010; 40: 1105-1111
  • 8 Kono T, Kaneko A, Omiya Y, Ohbuchi K, Ohno N, Yamamoto M. Epithelial transient receptor potential ankyrin 1 (TRPA1)-dependent adrenomedullin upregulates blood flow in rat small intestine. Am J Physiol 2013; 304: G428-G436
  • 9 Matsumoto J, Takeuchi K, Ueshima K, Okabe S. Role of capsaicin-sensitive afferent neurons in mucosal blood flow response of rat stomach induced by mild irritants. Dig Dis Sci 1992; 37: 1336-1344
  • 10 Raimura M, Tashima K, Matsumoto K, Tobe S, Chino A, Namiki T, Terasawa K, Horie S. Neuronal nitric oxide synthase-derived nitric oxide is involved in gastric mucosal hyperemic response to capsaicin in rats. Pharmacology 2013; 92: 60-70
  • 11 Wang S, Dai Y, Kogure Y, Yamamoto S, Zhang W, Noguchi K. Etodolac activates and desensitizes transient receptor potential ankyrin 1. Journal of Neurosci Res 2013; 91: 1591-1598
  • 12 Kono T, Shimada M, Yamamoto M, Kaneko A, Oomiya Y, Kubota K, Kase Y, Lee K, Uezono Y. Complementary and synergistic therapeutic effects of compounds found in Kampo medicine: analysis of daikenchuto. Front Pharmacol 2015; 6
  • 13 Kubota K, Ohtake N, Ohbuchi K, Mase A, Imamura S, Sudo Y, Miyano K, Yamamoto M, Kono T, Uezono Y. Hydroxy-α sanshool induces colonic motor activity in rat proximal colon: a possible involvement of KCNK9. Am J Physiol 2015; 308: G579-G590
  • 14 Tomohiro D, Mizuta K, Fujita T, Nishikubo Y, Kumamoto E. Inhibition by capsaicin and its related vanilloids of compound action potentials in frog sciatic nerves. Life Sci 2013; 92: 368-378
  • 15 Matsushita A, Ohtsubo S, Fujita T, Kumamoto E. Inhibition by TRPA1 agonists of compound action potentials in the frog sciatic nerve. Biochem Biophys Res Commun 2013; 434: 179-184
  • 16 Davis JB, Gray J, Gunthorpe MJ, Hatcher JP, Davey PT, Overend P, Harries MH, Latcham J, Clapham C, Atkinson K, Hughes SA, Rance K, Grau E, Harper AJ, Pugh PL, Rogers DC, Bingham S, Randall A, Sheardown SA. Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia. Nature 2000; 405: 183-187
  • 17 Kosugi M, Nakatsuka T, Fujita T, Kuroda Y, Kumamoto E. Activation of TRPA1 channel facilitates excitatory synaptic transmission in substantia gelatinosa neurons of the adult rat spinal cord. J Neurosci 2007; 27: 4443-4451
  • 18 Behrendt HJ, Germann T, Gillen C, Hatt H, Jostock R. Characterization of the mouse cold-menthol receptor TRPM8 and vanilloid receptor type-1 VR1 using a fluorometric imaging plate reader (FLIPR) assay. Br J Pharmacol 2004; 141: 737-745
  • 19 Horie S, Yamamoto H, Michael GJ, Uchida M, Belai A, Watanabe K, Priestley JV, Murayama T. Protective role of vanilloid receptor type 1 in HCl-induced gastric mucosal lesions in rats. Scand J Gastroenterol 2004; 39: 303-312
  • 20 Horie S, Michael GJ, Priestley JV. Co-localization of TRPV1-expressing nerve fibers with calcitonin-gene-related peptide and substance P in fundus of rat stomach. Inflammopharmacology 2005; 13: 127-137
  • 21 Horie S, Raimura M, Matsumoto K, Namiki T, Terasawa K, Priestley JV, Tahima K. Cooperative effects of neuronal nitric oxide synthase and endothelial nitric oxide synthase on gastric hyperemic response to intragastric capsaicin. In: Mozsik G, Abdel-Salam OME, Takeuchi K, eds. Capsaicin-Sensitive Neural Afferentation and the Gastrointestinal Tract: From Bench To Bedside 2014; 4: 103-124
  • 22 Kondo T, Obata K, Miyoshi K, Sakurai J, Tanaka J, Miwa H, Noguchi K. Transient receptor potential A1 mediates gastric distention-induced visceral pain in rats. Gut 2009; 58: 1342-1352
  • 23 Esplugues JV, Ramos EG, Gil L, Esplugues J. Influence of capsaicin-sensitive afferent neurons on the acid secretory responses of the stomach in vivo. Br J Pharmacol 1990; 100: 491-496
  • 24 Takeuchi K, Ishihara Y, Okada M, Niida H, Okabe S. A continuous monitoring of mucosal integrity and secretory activity in rat stomach: a preparation using a lucite chamber. Jpn J Pharmacol 1989; 49: 235-244
  • 25 Tashima K, Nakashima M, Kagawa S, Kato S, Takeuchi K. Gastric hyperemic response induced by acid back-diffusion in rat stomachs following barrier disruption-relation to vanilloid type-1 receptors. Med Sci Monit 2002; 8: BR157-BR163
  • 26 Christoph T, Gillen C, Mika J, Grünweller A, Schäfer MK, Schiene K, Frank R, Jostock R, Bahrenberg G, Weihe E, Erdmann VA, Kurreck J. Antinociceptive effect of antisense oligonucleotides against the vanilloid receptor VR1/TRPV1. Neurochem Int 2007; 50: 281-290
  • 27 Pomonis JD, Harrison JE, Mark L, Bristol DR, Valenzano KJ, Walker K. N-(4-Tertiarybutylphenyl)-4-(3-cholorphyridin-2-yl) tetrahydropyrazine-1 (2H)-carbox-amide (BCTC), a novel, orally effective vanilloid receptor 1 antagonist with analgesic properties: II. in vivo characterization in rat models of inflammatory and neuropathic pain. J Pharmacol Exp Ther 2003; 306: 387-393
  • 28 Yonei Y, Holzer P, Guth PH. Laparotomy-induced gastric protection against ethanol injury is mediated by capsaicin-sensitive sensory neurons. Gastroenterology 1990; 99: 3-9