Elucidation of mechanisms for the generation of gut peristaltic reflex using various types of knockout mice.

2012 Fiscal Year Final Research Report

• Project/Area Number: 22380159
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Basic veterinary science/Basic zootechnical science
• Research Institution: Gifu University
• Principal Investigator: KOMORI Seiichi 岐阜大学, 応用生物科学部, 名誉教授 (70195866)
• Co-Investigator(Kenkyū-buntansha): UNNO Toshihiro 岐阜大学, 応用生物科学部, 教授 (90252121) ; KITAZAWA Takio 酪農学園大学, 獣医学部, 教授 (50146338) ; IINO Satoshi 福井大学, 医学部, 教授 (40242854) ; MATUYAMA Hayato 岐阜大学, 応用生物科学部, 准教授 (80345800) ; TANAHASHI Yasuyuki 京都産業大学, 総合生命科学部, 助教 (60582418)
• Research Collaborator: JURGEN Wess National Institute of Diabets and Digestive and Kidney Diseases. ; YAMADA Masahisa 沖縄科学技術研究基盤整備機構, コモンリソースグループ ; SAKAI Hiroki 岐阜大学, 応用生物科学部, 准教授 ; SAITOH Shouchirou 岐阜大学, 応用生物科学部, 准教授 ; ANDOH Kumiko 岐阜大学, 応用生物科学部, 学部学生 ; KIMURA Kaori 岐阜大学, 応用生物科学部, 学部学生 ; SUGIYAMA Kyoko 岐阜大学, 応用生物科学部, 学部学生 ; MATSUI Ryuusuke 岐阜大学, 応用生物科学部, 学部学生 ; KATSURADA Taisuke 岐阜大学, 応用生物科学部, 学部学生 ; NAITO Kiyiotada 岐阜大学, 応用生物科学部, 学部学生 ; SOBUE Yuki 岐阜大学, 応用生物科学部, 学部学生 ; NAGANO Hiroshi 岐阜大学, 応用生物科学部, 学部学生 ; WAKATA Tomohiro 岐阜大学, 応用生物科学部, 学部学生
• Project Period (FY): 2010 – 2012
• Keywords: 消化管 / 蠕動運動 / ノックアウトマウス / コリン作動性神経 / カハール間質細胞 / ムスカリン受容体 / 受容体サブタイプ

Research Abstract

The cholinergic neurons play an important rolein the generation and regulation of gut peristaltic reflex. Acetylcholine released from the cholinergic neurons act on muscarinic receptors in various neurons and smooth muscles to produce peristalsis. However, the precise roles of muscarinic receptor subtypes have not yet been elucidated. In the present study, we analyzed gut peristalsis in muscarinic receptor subtype knockout mice. The results suggest that M2 subtype of muscarinic receptor plays an essential role in the generation of peristalsis and that this subtype may be a useful target for the development of new drugs to treat for various intestinal disorders, such as irritable bowel syndrome.

Research Products

• [Journal Article] Evidence for M2and M3muscarinic receptor involvement in cholinergic excitatory junction potentials through synergistic activation of cation channels in the longitudinal muscle of mouse ileum (2013)
  • Author(s): Matsuyama, H., Tanahashi, Y., Kitazawa, T., Yamada, M., Komori, S., Unno, T
  • Journal Title: J. Pharmacol. Sci. Volume: 121 Pages: 227-236
  • DOI: DOI:10.1254/jphs. 12231FP
  • Peer Reviewed
• [Journal Article] A ganglionic stimulant, 1,1-dimethyl-4-phenylpiperazinium, caused both cholinergic and adrenergic responses in the isolated mouse atrium (2013)
  • Author(s): Ochi, K., Teraoka, H., Unno, T., Komori, S., Yamada, M., Kitazawa, T
  • Journal Title: Eur. J. Pharmacol. Volume: 704 Pages: 7-14
  • DOI: DOI:10.1016/j.ejphar.2013.02.019.
  • Peer Reviewed
• [Journal Article] Age- dependent reduction of ghrelin- and motilin-induced contractile activity in the chicken gastrointestinal tract (2013)
  • Author(s): Kitazawa, K., Yoshida, A., Tamano, T., Teraoka, H., Kaiya, H
  • Journal Title: Peptides Volume: 43 Pages: 88-95
  • DOI: DOI:10.1016/j.ygcen. 2012.06.025.
  • Peer Reviewed
• [Journal Article] Immunohistochemical and functional studies for M3 muscarinic receptors and cyclooxygenase-2 expressed in the mouse atrium. (2012)
  • Author(s): Harada, N., Ochi, K., Yaosaka, N., Teraoka, H., Hiraga, T., Iwanaga, T., Unno, T., Komori, S., Yamada, M., Kitazawa, T.
  • Journal Title: Auton. Autacoid Pharmacol. Volume: 32 Pages: 41-52
  • DOI: DOI:10.1111/j.1474-8673.2012.00472. x
  • Peer Reviewed
• [Journal Article] Ghrelin does not affect gastrointestinal contractility in rainbow trout and goldfish in vitro. (2012)
  • Author(s): Kitazawa, T., Itoh, K., Yaosaka, N., Maruyama, K., Matsuda, K., Teraoka, H., Kaiya, H.
  • Journal Title: General Comp. Endocrinol. Volume: 178 Pages: 539-545
  • DOI: DOI:10.1016/j.ygcen.2012.06.025.
  • Peer Reviewed
• [Journal Article] Molecular identification of ghrelin receptor (GHS-R1a) and its functional role in the gastrointestinal tract of the guinea-pig. (2011)
  • Author(s): Kitazawa T., Nakamura T., Saeki A., Teraoka H., Hiraga T., Kaiya H
  • Journal Title: Peptides Volume: 32 Pages: 1876-1886
  • DOI: DOI:10.1016/j.peptides.2011.07.026
  • Peer Reviewed
• [Journal Article] Muscarinic receptor subtypes involved in regulation of colonic motility in mice: functional studies using muscarinic receptor-deficient mice (2011)
  • Author(s): Kondo, T., Nakajima, M., Teraoka, H., Unno, T., Komori, S., Yamada, M., Kitazawa, T
  • Journal Title: Eur. J. Pharmacol. Volume: 670 Pages: 236-243
  • DOI: DOI:10.1016/j.ejphar.2011.08. 03410.1016/j.ejphar.2011.08.034
  • Peer Reviewed
• [Journal Article] Interstitial cells of Cajal in the gastrointestinal musculature of W (jic) c-kit mutant mice (2011)
  • Author(s): Iino S., Horiguchi S., Horiguchi K
  • Journal Title: J Smooth Muscle Res. Volume: 47 Pages: 111-121
  • DOI: DOI:10.1540/jsmr.47.111
  • Peer Reviewed
• [Journal Article] Serotonin Augments Gut Pacemaker Activity via 5-HT3 receptors. (2011)
  • Author(s): Liu H.N., Ohya S., Nishizawa Y., Sawamura K., Iino S., Syed M.M., Goto K., Imaizumi Y., Nakayama S
  • Journal Title: PLoS ONE Volume: 6 Pages: e24928(10)
  • DOI: DOI:10.1371/journal.pone.002492 8
  • Peer Reviewed
• [Journal Article] Nitrergic inhibition of tachykininergic neuro-muscular transmission via cyclic GMP in the hamster ileum. (2011)
  • Author(s): Matsuyama, H., Unno, T., Komori, S., Takewaki T
  • Journal Title: J. Vet. Med. Sci. Volume: 73 Pages: 453-458
  • DOI: DOI:http://dx.DOI:.org/10.1292/jvms.10-0425
  • Peer Reviewed
• [Journal Article] Colon-specific contractile responses to tetrodotoxin in the isolated mouse gastrointestinal tract (2011)
  • Author(s): Okuno, Y, Kondo, T, Saeki, A, Uchida, E, Teraoka, H, Kitazawa, T
  • Journal Title: Auton. Autacoide Pharmacol Volume: 31 Pages: 20-30
  • DOI: DOI:10.1111/j.1474- 8673.2011.00462.x.
  • Peer Reviewed
• [Journal Article] Ouabain exacerbates botulinum neurotoxin-induced muscle paralysis via progression of muscle atrophy in mice. (2010)
  • Author(s): Fujikawa, R., Muroi, Y., Unno, T., Ishii, T
  • Journal Title: J. Toxicol. Sci. Volume: 35 Pages: 795-805
  • DOI: DOI:http://dx.DOI:.org/10.2131/jts.35.795
  • Peer Reviewed
• [Journal Article] Properties of acetylcholine-induced relaxation of smooth muscle isolated from the proximal colon of the guinea-pig (2010)
  • Author(s): Kodama, Y., Iino, S., Shigemasa, Y., Suzuki, H.
  • Journal Title: J. Smooth Muscle Res. Volume: 46 Pages: 185-200
  • DOI: DOI:http://dx.DOI:.org/ 10.1540/ jsmr.46.185
  • Peer Reviewed
• [Journal Article] Muscarinic receptor subtypes mediating Ca2+sensitization of intestinal smooth muscle contraction; studies with mutant mice lacking the receptor subtypes (2010)
  • Author(s): Suguro, M., Matsuyama, H., Unno, T., Tanahashi, Y., Kitazawa, T., Yamada, M., Komori. S
  • Journal Title: J. Vet. Med. Sci Volume: 72 Pages: 443-451
  • DOI: DOI:http://dx.DOI:.org/ 10.1292/jvms.09-0458
  • Peer Reviewed
• [Journal Article] Downregulation of msh-like 2 (msx2) and neurotrophic tyrosine kinase receptor type 2 (ntrk2) in the developmental gut of KIT mutant mice (2010)
  • Author(s): Horiguchi, S., Horiguchi, K., Nojyo, Y., Iino, S
  • Journal Title: Biochem. Biophy. Res. Comm. Volume: 396 Pages: 774-779
  • DOI: DOI:10.1016/j.bbrc.2010.05. 030.
  • Peer Reviewed
• [Presentation] Involvement of M2 or M3 muscarinic receptor-coupled signall- ing molecules in the activation of muscarinic cation channels in mouse ileal smooth muscle cells (2013)
  • Author(s): 海野年弘他
  • Organizer: 第86回日本薬理学会総会
  • Place of Presentation: 福岡
  • Year and Date: 20130321-23
• [Presentation] Muscarinic regulation of ATP sensitive K+ channels in mouse ileal smooth muscles (2013)
  • Author(s): 棚橋靖行他
  • Organizer: 第86回日本薬理学会総会
  • Place of Presentation: 福岡
  • Year and Date: 20130321-23
• [Presentation] Interstitial cells of Cajal in c-Kit mutant mice. (2012)
  • Author(s): Iino, S.他
  • Organizer: The 7th international symposium on ICC
  • Place of Presentation: Florence (Italy)
  • Year and Date: 20120902-05
• [Presentation] Interstitial cells of Cajal in c-Kit signal deficient W-sash mutant mice (2012)
  • Author(s): Iino, S.他
  • Organizer: The 14th International Congress of Histochemistry and Cytochemistry
  • Place of Presentation: Kyoto (Japan)
  • Year and Date: 20120826-29
• [Presentation] Morphologicaland functional properties of fibroblast-like cells in the gastrointestinal musculature (2012)
  • Author(s): Iino S.他
  • Organizer: 第89回 日本生理学会総会
  • Place of Presentation: 松本
  • Year and Date: 2012-03-30
• [Presentation] A gabglion stimulant, 1,1 dimethyl-4 phenyl- piperazinium iodide (DMPP) stimulates both cholinergic and adrenergic neurons in isolated atrium of the mouse (2012)
  • Author(s): Ochi K.他(Unno T)
  • Organizer: 第85回日本薬理学会年会
  • Place of Presentation: 京都
  • Year and Date: 2012-03-16
• [Presentation] Role of T type Ca2+channels in myenteric AH neurons of the guinea-pig ileum. (2012)
  • Author(s): Hayato M., NguyenT., Unno T., Komori S., Thacker M., Pontell L., Hunne B., Nurgali K., Furness J
  • Organizer: 第85回日本薬理学会年会
  • Place of Presentation: 京都
  • Year and Date: 2012-03-15
• [Presentation] Neuronal M_1muscarinic receptor mediates inhibition of mouse colonic motility through activation of nitrergic nerves (2012)
  • Author(s): Kondo K.他(Unno T)
  • Organizer: 第85回日本薬理学会年会
  • Place of Presentation: 京都
  • Year and Date: 2012-03-14
• [Presentation] マウス胎生期消化管におけるc-Kit 受容体型チロシンキナーゼ発現の解析 (2011)
  • Author(s): 飯野哲他
  • Organizer: 第52回日本組織細胞化学会総会
  • Place of Presentation: 金沢
  • Year and Date: 2011-09-24
• [Presentation] c-Kit を発現しない Wsh ミュータントマウスにおけるカハール介在細胞. (2011)
  • Author(s): 飯野哲他
  • Organizer: 第52回日本組織細胞化学会総会
  • Place of Presentation: 金沢
  • Year and Date: 2011-09-24
• [Presentation] 過活動膀胱モデルマウスの膀胱における神経刺激収縮反応の変化 (2011)
  • Author(s): 海野年弘他
  • Organizer: 第152回日本獣医学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2011-09-20
• [Presentation] モルモット回腸の筋層間神経細胞における T-型電位依存性 Ca2+チャネルの役割. (2011)
  • Author(s): 松山勇人他
  • Organizer: 第152回日本獣医学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2011-09-20
• [Presentation] マウス消化管筋層における線維芽細胞様細胞の組織学的検討 (2011)
  • Author(s): 飯野哲他
  • Organizer: 第53回日本平滑筋学会総会
  • Place of Presentation: 東京
  • Year and Date: 2011-08-04
• [Presentation] c-Kit 遺伝子異常を持つ W ミュータントマウスにおける消化管カハール介在細胞 (2011)
  • Author(s): 飯野哲他
  • Organizer: 第53回日本平滑筋学会総会
  • Place of Presentation: 東京
  • Year and Date: 2011-08-03
• [Presentation] ICC and fibroblast-like cells: Interstitial cells in the gastrointestinal musculature (2011)
  • Author(s): Iino S.他
  • Organizer: 第116回 日本解剖学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2011-03-30
• [Presentation] ハムスター小腸のタキキニン作動性神経-平滑筋間の情報伝達に対するNO作動性神経による抑制機構 (2011)
  • Author(s): 松山勇人他
  • Organizer: 第151回日本獣医学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2011-03-30
• [Presentation] Role of M3 muscarinic receptor-coupled signalling molecule in the activation of muscarinic cation channels in mouse ileal smooth muscle cells (2011)
  • Author(s): Unno, T.他
  • Organizer: 第84回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-03-23
• [Presentation] マウス回腸平滑筋細胞のムスカリン作動性陽イオンチャネルの活性化におけるM3受容体サブタイプに連関した情報伝達分子の役割 (2010)
  • Author(s): 海野年弘他
  • Organizer: 第150回日本獣医学会学術集会
  • Place of Presentation: 帯広
  • Year and Date: 2010-09-16
• [Presentation] マウス回腸縦走筋標本におけるムスカリン作動性収縮に対するカハール細胞の役割 (2010)
  • Author(s): 棚橋靖行他
  • Organizer: 第150回日本獣医学会学術集会
  • Place of Presentation: 帯広
  • Year and Date: 2010-09-16
• [Presentation] c-Kit 遺伝子異常を持つ W ミュータントマウスにおける消化管カハール介在細胞 (2010)
  • Author(s): 飯野哲他
  • Organizer: 第51回日本組織細胞化学会総会
  • Place of Presentation: 東京
  • Year and Date: 2010-09-04
• [Remarks]
  • URL: http://www1.gifu-u.ac.jp/~pharmaco/index.htm