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2007 Fiscal Year Final Research Report Summary

Functional analysis of acetylcholine receptor using muscarinic receptor knockout mice.

Research Project

Project/Area Number 18390073
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionDoshisha Women's College of Liberal Arts (2007)
The University of Tokyo (2006)

Principal Investigator

FUJII Takeshi  Doshisha Women's College of Liberal Arts, Faculty of Pharmaceutical Sciences, Associate Professor (80255380)

Co-Investigator(Kenkyū-buntansha) TAKATORI Yuki  Doshisha Women's College of Liberal Arts, Faculty of Pharmaceutical Sciences, Research Associate (90411090)
YAMADA Shizuo  University of Shizuoka, Faculty of Pharmaceutical Sciences, Professor (80106434)
TAKEUCHI Tadayoshi  Osaka Prefecture University, Grad Sch Life Env Sci, Professor (00171611)
MATSUI Minoru  Chiba Institute of Science, Faculty of Pharmacy, Associate Professor (50282611)
KAWASHIMA Koichiro  Musashino University, Faculty of Pharmacy, Visiting Professor (70095008)
Project Period (FY) 2006 – 2007
KeywordsPharmacology / Pharmaceutical Sciences / Neuroscience / Brain and Neuron / Bioactive molecule / Acetylcholine / Receptor
Research Abstract

Muscarinic acetylcholine receptor (mAChR) knockout (KO) mice, which were developed and supplied by Dr Matsui (Chiba Institute of Science), were used. Regulation of Immunological response: On the 14th day after immunization, serum antigen specific IgG_1 levels in M_1/M5-KO mice were significantly lower than those of wild-type mice. In addition, concanavalin A-induced ChAT, an ACh-synthesizing enzyme, interleukin-2 and c-fos mRNA expression in wild-type mice. These gene expressions were significantly reduced, in M_3 KO-mice, when compared with those of wild-type mice. These findings suggested that M_1/M_5 and M_3 mAChR may involved in regulation of lymphocyte function. Relaxation of Urinary bladder muscle: In wild-type mice, carbachol (CCh) relaxed noradrenaline-induced contraction in a dose-dependent manner. However, relaxation by CCh was decreased in M_3-KO mice, but not changed in M_2-KO mice. In addition, CCh-induced response was antagonized by indomethacin. In addition, PGE_2 induce … More d concentration dependent relaxation. These findings suggest that M_3 mAChR and PGE_2 are involved in relaxation of urinary bladder muscle. Changes in mAChR ligand properties: Characterization of mAChR binding activity in the bladder and submandibular gland after oral administration of oxybutynin (Oxy) and solifenacin (Sol) to M_2-KO mice was performed. There was little difference between bladder and submandibular gland of M_2-KO mice in in vitro mAChR binding activities of Oxy and Sol, suggesting equal affinity to the residual (predominantly M_3) mAChR in both tissues. In contrast, compared with that after oral Oxy, oral Sol exerted significantly greater binding activity to the bladder mAChR of M_2-KO mice, whereas oral Sol exhibited significantly smaller binding activity to the exocrine gland mAChR. These data indicate that oral Sol, unlikely oral, may exert greater binding to M_3 mAChR of bladder than exocrine gland under in vivo condition. Oral Sol may be advantageous for the treatment of overactive bladder, in terms of high selectivity to bladder. Less

  • Research Products

    (42 results)

All 2008 2007 2006 Other

All Journal Article (24 results) (of which Peer Reviewed: 12 results) Presentation (18 results)

  • [Journal Article] Basic and clinical aspects of non-neuronal acetylcholine:expression of and independent,non-neuronal cholinergic system in lymphocytes and its clinical significance in immunotherapy2008

    • Author(s)
      Fujii T
    • Journal Title

      Journal of Pharmacological Sciences 106

      Pages: 186-192

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Basic and clinical aspects of non-neuronal acetylcholine:overview of non-neuronal cholinergic systems and their biological significance2008

    • Author(s)
      Kawashima K
    • Journal Title

      Journal of Pharmacological Sciences 106

      Pages: 167-173

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Basic and clinical aspects of non-neuronal acetylcholine : Overview of Non-neuronal cholinergic system and its biological significance.2008

    • Author(s)
      Kawashima K
    • Journal Title

      J. Fharmacol. Sci. 106

      Pages: 167-173

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] in immunotherapy. Basic and clinical aspects of non-neuronal acetylcholine : Expression of an independent, non-neruronal cholinergic system in lymphocytes and its clinical significance in immunotherapy.2008

    • Author(s)
      Fujii T
    • Journal Title

      J. Pharmacol. Sci. 106

      Pages: 186-192

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Muscarinic receptor knockout mice confirm involvement of M_3 receptor in endothelium-dependent vasodilation in mouse arteries.2008

    • Author(s)
      Beny J-L
    • Journal Title

      J. Cardiovasc. fharmacol. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] M_2 and M_3 muscarinic receptors are involved in enteric nerve-mediated contraction of the mouse ileum:findings obtained using muscarinic receptor knockout mouse2007

    • Author(s)
      Takeuchi T
    • Journal Title

      American Journal of Physiology Gastrointestinal and Liver Physiology 292

      Pages: G154-G164

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Upregulated PAR-2-mediated salivary secretion in mice deficient in muscarinic acetylcholine receptor subtypes2007

    • Author(s)
      Nishiyama T
    • Journal Title

      Journal of Pharmacology and Experimental Therapeutics 320

      Pages: 516-524

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Tonic enhancement of endocannabinoid-mediated retrograde suppression of inhibition by cholinergic interneuron activity in the striatum2007

    • Author(s)
      Narushima M
    • Journal Title

      Journal of Neuroscience 27

      Pages: 496-506

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Alternative poly(A) site-selection regulates the production of alternatively splicedvesl-1/homer1 isoforms that encode postsynaptic scaffolding proteins2007

    • Author(s)
      Niibori Y
    • Journal Title

      Neuroscience Research 57

      Pages: 399-410

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Neuronally released acetylcholine acts on the M2 muscarinic receptor to oppose the relaxant effect of isoproterenol on cholinergic contractions in mouse urinary bladder2007

    • Author(s)
      Ehlert FJ
    • Journal Title

      Journal of Pharmacology and Experimental Therapeutics 322

      Pages: 631-637

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Diminished antigen-specific IgG1 and interleukin-6 production and acetylcholinesterase expression in combined M1 and M5 muscarinic acetylcholine receptor knockout mice2007

    • Author(s)
      Fujii YX
    • Journal Title

      Journal of Neuroimmunology 188

      Pages: 80-85

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Diminished antigen-specific IgG, and interleukin-6 production and acetylcholinesterase expression in combined M_1 and M_5 muscarinic acetylcholine receptor knockout mice.2007

    • Author(s)
      Fujii YX
    • Journal Title

      J. Neurvimmanol. 185

      Pages: 80-85

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] M_2 and M_3 muscarinic receptors are involved in enteric nerve-mediated contraction of the mouse ileum : findings obtained using muscarinic receptor knockout mouse.2007

    • Author(s)
      Takeuchi T
    • Journal Title

      Am. J. Physiol. Gastrointest. Liver Physiol 292

      Pages: G154-G164

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Upregulated PAR-2-mediated salivary secretion in mice deficient in muscarinic acetylcholine receptor subtypes.2007

    • Author(s)
      Nishiyama T
    • Journal Title

      J. Marmacol. Exp. Than 320

      Pages: 516-524

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Tonic enhancement of endocannabinoid-mediated retrograde suppression of inhibition by cholinergic interneuron activity in the striatum.2007

    • Author(s)
      Narushima M
    • Journal Title

      J. Neurosci. 27

      Pages: 496-506

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Alternative poly(A) site-selection regulates the production of alternatively spliced ves1-1/homerl isoforms that encode postsynaptic scaffolding proteins.2007

    • Author(s)
      Niibori Y
    • Journal Title

      Neurosci. Res. 57

      Pages: 399-410

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Neuronally released acetylcholine acts on the M_2 muscarinic receptor to oppose the relaxant effect of isoproterenol on cholinergic contractions in mouse urinary bladder.2007

    • Author(s)
      Eillert FJ
    • Journal Title

      J. fharmacol. Exp. Ther. 322

      Pages: 631-637

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Involvement of M_2 muscarinic receptors in relaxant response of circular muscle of mouse gastric antrum2006

    • Author(s)
      Takeuchi T
    • Journal Title

      Neurogastroenterology and Motility 18

      Pages: 226-233

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Opposing functions of spinal m2,m3,and m4 receptor subtypes in regulation of GABAergic inputs to dorsal horn neurons revealed by muscarinic receptor knockout mice2006

    • Author(s)
      Zhang HM
    • Journal Title

      Molecular Pharmacology 69

      Pages: 1048-1055

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Differential coupling of muscarinic M_1,M_2 and M_3 receptors to phosphoinositide hydrolysis in urinary bladder and longitudinal muscle of the ileum of the mouse2006

    • Author(s)
      Tran JA
    • Journal Title

      Journal of Pharmacology and Experimental Therapeutics 318

      Pages: 649-656

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Involvement of M_2 muscarinic receptors in relaxant response of circular muscle of mouse gastric antrum.2006

    • Author(s)
      Takeuchi T
    • Journal Title

      Neurogastroenterol. Motil 18

      Pages: 226-233

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Opposing functions of spinal m2, m3, and m4 receptor subtypes in regulation of GABAergic inputs to dorsal horn neurons revealed by muscarinic receptor knockout mice.2006

    • Author(s)
      Zhang HM
    • Journal Title

      Mol. Pharmacol. 69

      Pages: 1048-1055

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Differential coupling of muscarinic M_1, M_2 and M_3 receptors to phosphoinositide hydrolysis in urinary bladder and longitudinal muscle of the ileum of the mouse.2006

    • Author(s)
      Tran JA
    • Journal Title

      J. Pharmacol. Exp. Ther 318

      Pages: 649-656

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Muscarinic receptor knockout mice confirm involvement of M_3 receptor in endothelium-dependent vasodilation in mouse arteries

    • Author(s)
      Beny J-L
    • Journal Title

      Journal of Cardiovascular Pharmacology (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Presentation] 神経外コリン作動系2008

    • Author(s)
      藤井 健志
    • Organizer
      第3回 医工薬産学公連携フォーラム
    • Place of Presentation
      京都
    • Year and Date
      2008-02-01
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Non-neuronal cholinergic systems in lymphocytes.2008

    • Author(s)
      Fujii T
    • Organizer
      3rd Forum of Medicine, Technology and Pharmacy in Kyoto
    • Place of Presentation
      Kyoto
    • Year and Date
      2008-02-01
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] マウス膀胱括約筋でのムスカリン受容体活性化による弛緩機構2007

    • Author(s)
      河崎 哲也
    • Organizer
      第49回日本平滑筋学会総会
    • Place of Presentation
      橿原
    • Year and Date
      2007-07-05
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Relaxation mechanisms of mouse urinary bladder muscle via muscarinic acetylcholine receptor.2007

    • Author(s)
      Kawasaki T
    • Organizer
      49th Annual Meeting of JapaneseSociety
    • Place of Presentation
      Kashihara
    • Year and Date
      2007-07-05
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] マウス膀胱括約筋におけるムスカリン受容体を介した弛緩機構の解明2007

    • Author(s)
      河崎 哲也
    • Organizer
      第111回日本薬理学会近畿部会
    • Place of Presentation
      名古屋
    • Year and Date
      2007-06-15
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Relaxation mechanisms of the sphincter muscle via muscarinic acetylcholine receptor in mouse urinary bladder.2007

    • Author(s)
      Kawashi T
    • Organizer
      111th Kink Regional Meeting of Japanese Pharmacological Society
    • Place of Presentation
      Nagoya
    • Year and Date
      2007-06-15
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] ムスカリン性受容体M2欠損マウスを用いた過活動性膀胱治療薬のムスカリン性受容体結合動態の解析2007

    • Author(s)
      Luvasandorj O
    • Organizer
      第80回日本薬理学会年会
    • Place of Presentation
      名古屋
    • Year and Date
      2007-03-16
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] 膀胱選択的ムスカリン受容体拮抗薬コハク酸ソリフェナシン(ベシケア◎)の基礎と臨床2007

    • Author(s)
      山田 静雄
    • Organizer
      第80回日本薬理学会年会
    • Place of Presentation
      名古屋
    • Year and Date
      2007-03-16
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Characterization of muscarinic receptor(mR) binding oral administration of anticholinergic agents in muscarinic M_2 knockout mice.2007

    • Author(s)
      Luvasandorj O
    • Organizer
      80th Annual Meeting of Japanese Pharmacological Society
    • Place of Presentation
      Nagoya
    • Year and Date
      2007-03-16
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Muscarinic receptor binding characteristics of novel anticholinergic agents directed toward the therapy of overactive bladder.2007

    • Author(s)
      Yamada S
    • Organizer
      80th Annual Meeting of Japanese Pharmacological Society
    • Place of Presentation
      Nagoya
    • Year and Date
      2007-03-16
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] リンパ球における非神経性AChの発現と免疫治療における臨床的意義2007

    • Author(s)
      藤井 健志
    • Organizer
      第80回日本薬理学会年会
    • Place of Presentation
      名古屋
    • Year and Date
      2007-03-15
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] 非神経性アセチルコリンの病態生理学的意義:概説2007

    • Author(s)
      川島 紘一郎
    • Organizer
      第80回日本薬理学会年会
    • Place of Presentation
      名古屋
    • Year and Date
      2007-03-15
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Pathological significance of non-neuronal acetylcholine : an overview.2007

    • Author(s)
      Kawashima K
    • Organizer
      80th Annual Meeting of Japanese Pharmacological Society
    • Place of Presentation
      Nagoya
    • Year and Date
      2007-03-15
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Expression of non-neuronal acetylcholine in lymphocytes and its clinical significance in immunotherapy.2007

    • Author(s)
      Fujii T
    • Organizer
      80th Annual Meeting of Japanese Pharmacological Society
    • Place of Presentation
      Nagoya
    • Year and Date
      2007-03-15
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Roles of Lymphocyte function-associated antigen-1 (LFA-1)in regulation of Lymphocytic cholinergic activity2006

    • Author(s)
      藤井 健志
    • Organizer
      2nd International Symposium on Non-neuronal Acetylcholine
    • Place of Presentation
      ドイツ・マインツ
    • Year and Date
      2006-09-02
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Roles of lymphocyte function-associated antigen-1(LFA-1) in regulation of lymphocytic cholinergic activity.2006

    • Author(s)
      Fujii T
    • Organizer
      2nd International Symposium on Non-neuronal Acetylcholine
    • Place of Presentation
      Mainz, Germany
    • Year and Date
      2006-09-02
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] T 細胞におけるムスカリンおよびニコチン受容体を介するカルシウムシグナル2006

    • Author(s)
      藤井 健志
    • Organizer
      第29回日本神経科学会年会
    • Place of Presentation
      京都
    • Year and Date
      2006-07-21
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Ca^<2+> signals via muscarinic and nicotinic receptors in T cells.2006

    • Author(s)
      Fujii T
    • Organizer
      29th Annual Meeting of the Japanese Neuroscience Society
    • Place of Presentation
      Kyoto
    • Year and Date
      2006-07-21
    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2010-02-04  

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