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2010 Fiscal Year Final Research Report

Reseaarch on the function and development of new therapy for Ion channels in the lower urinary tract

Research Project

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Project/Area Number 20390423
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionUniversity of Yamanashi

Principal Investigator

TAKEDA Masayuki  University of Yamanashi, 大学院・医学工学総合研究部, 教授 (80197318)

Co-Investigator(Kenkyū-buntansha) ARAKI Isao  滋賀医科大学, 医学部, 准教授 (50252424)
ZAKOUJI Hidenori  山梨大学, 大学院・医学工学総合研究部, 助教 (60345717)
KOBAYASHI Hideki  山梨大学, 大学院・医学工学総合研究部, 助教 (50402053)
YOSHIYAMA Mitsuharu  山梨大学, 大学院・医学工学総合研究部, 医学研究員 (20422694)
TOMINAGA Makoto  大学共同利用機関法人自然科学研究機構(共通施設), 教授 (90260041)
FUKASAWA Mizuya  山梨大学, 医学部附属病院, 講師 (80252039)
MOCHIZUKI Tsutomu  山梨大学, 大学院・医学工学総合研究部, 医学研究員 (50377496)
SAWADA Norifumi  山梨大学, 医学部附属病院, 助教 (70402055)
TSUCHIDA Takayuki  山梨大学, 医学部附属病院, 講師 (30217327)
Project Period (FY) 2008 – 2010
Keywordsイオンチャネル / 膀胱上皮細胞 / 細胞内カルシウムイオン / TRP TRPV4
Research Abstract

In the urine storage phase, mechanical stretch stimulates bladder afferents. These urinary bladder afferent sensory nerves consist of small diameter Aδ- and C-fibers running in the hypogastic and pelvic nerves. Neuroanatomical studies have revealed a complex neuronal network within the bladder wall. The exact mechanisms that underline mechano-sensory transduction in bladder afferent terminals remain ambiguous ; however, a wide range of ion channels (e.g. TTX-resistant Na+ channels, Kv channels and hyperpolarization-activated cyclic nucleotidegated cation channels, degenerin/epithelial Na+ channel), and receptors (e.g. TRPV1, TRPM8, TRPA1, P2X2/3, etc.) have been identified at bladder afferent terminals and have implicated in the generation and modulation of afferent signals, which are elcited by a wide range of bladder stimulations including physiological bladder filling, noxious distension, cold, chemical irritation and inflammation. The mammalian transient receptor potential (TRP) family consists of 28 channels that can be subdivided into six different classes : TRPV (vanilloid), TRPC (canonical), TRPM (Melastatin), TRPP (Polycystin), TRPML (Mucolipin), and TRPA (Ankyrin). TRP channels are activated by a diversity of physical (voltage, heat, cold, mechanical stress) or chemical (pH, osmolality) stimuli and by binding of specific ligands, enabling them to act as multifunctional sensors at the cellular level. TRPV1, TRPV2, TRPV4, TRPM8, and TRPA1 have been described in different parts of the urogenital tract. Although only TRPV1 among TRPs has been extensively studied so far, more evidence is slowly accumulating about the role of other TRP channels, ion channels, and receptors in the pathophysiology of the urogenital tract, and may provide a new strategy for the treatment of bladder dysfunction.

  • Research Products

    (25 results)

All 2011 2010 2009 2008 Other

All Journal Article (16 results) (of which Peer Reviewed: 16 results) Presentation (7 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Characterization of muscarinic receptors in the human bladder mucosa: Direct quantification of subtypes using 4-DAMP mustard.2011

    • Author(s)
      Akira Yoshida, Masanao Seki, Sweety Nasrin, Atsushi Otsuka, Seiichiro Ozono, Masayuki Takeda, Keisuke Masuyama, Isao Araki, Frederick J Ehlert, shizuo Yamada
    • Journal Title

      Urology in press

    • Peer Reviewed
  • [Journal Article] Muscarinic receptor binding of Imidafenacin in human bladder mucosa and detrusor and parathyroid.2011

    • Author(s)
      Masanao Seki, Masaki Ogoda, Shiori Kuraoka, Atsushi Otsuka, Seiichiro Ozono, Masayuki Takeda, Keisuke Masuyama, Isao Araki, Shizuo Yamada
    • Journal Title

      LUTS in press

    • Peer Reviewed
  • [Journal Article] Solifenacin as add-on therapy for overactive bladder symptoms ? ASSIST, randomized controlled study - Urology2011

    • Author(s)
      Osamu Yamaguchi, Hidehiko Kakizaki, Yukio Homma, Masayuki Takeda, Osamu Nishizawa, Momokazu Gotoh, Osamu Yokoyama, Narihito Seki, Masaki Yoshida on behalf of the ASSIT Study Group
    • Journal Title

      randomized controlled study - Urology

    • Peer Reviewed
  • [Journal Article] The Japanese Naftopidil Neurogenic Lower Urinary Tract Dysfunction Study Group.2011

    • Author(s)
      Masayuki Takeda, Yukio Homma, Isao Araki, Hidehiro Kakizaki, Tomonori Yamanishi, Takashi Yokota, Momokazu Gotoh, Yasuhiko Igawa, Narihito Seki, Mineo Takei, Masaki Yoshida, Kimio Sugaya, Osamu Nishizawa.
    • Journal Title

      PREDICTIVE FACTORS FOR THE EFFECT OF ALPHA1- D/A ADRENOCEPTOR ANTAGONIST, NAFTOPIDIL, ON SUBJECTIVE AND OBJECTIVE PARAMETERS IN PATIENTS WITH NEUROGENIC LOWER URINARY TRACT DYSFUNCTION. BJU Int.

    • Peer Reviewed
  • [Journal Article] Functional roles of TRPV1 channels in lower urinary tract irritated by acetic acid2010

    • Author(s)
      Mitsuharu Yoshiyama, Isao Araki, Hideki Kobayashi, Hidenori Zakoji, Masayuki Takeda
    • Journal Title

      in-vivo evaluations on the sex difference in decerebrate unanesthetized mice Am J Physiol Regul Integr Comp Physiol 298

      Pages: 1351-1359

    • Peer Reviewed
  • [Journal Article] The TRPV4 cation channel mediates stretch-evoked Ca2^+ influx and ATP release in primary urothelial cell cultures.2009

    • Author(s)
      Mochizuki T, Sokabe T. Araki I, Fujishita K, Shibasaki K, Uchida K, Naruse K, Koizumi S, Takeda M, Tominaga M
    • Journal Title

      J.Biological Chemistry 284

      Pages: 21257-21264

    • Peer Reviewed
  • [Journal Article] Sex differences in the expression profile of acid-sensing ion channels in the mouse urinary bladder: a possible involvement in irritative bladder symptoms.2009

    • Author(s)
      Kobayashi, H., Yoshiyama, M., Zakoji, H., Takeda, M., Araki, I.
    • Journal Title

      BJU Int. 104

      Pages: 1746-1751

    • Peer Reviewed
  • [Journal Article] Suppression of NF-kappaB by cyclosporin a and tacrolimus (FK506) via induction of the C/EBP family : implication for unfolded protein response2009

    • Author(s)
      Du, S., Hiramatsu, N., Hayakawa, K.,Kasai, A., Okamura, M., Huang, T., Yao, J.,Takeda, M., Araki, I., Sawada, N., Paton,A.W., Paton, J.C., Kitamura, M.
    • Journal Title

      J.Immunol. 182

      Pages: 7201-7211

    • Peer Reviewed
  • [Journal Article] Differential expression profile of cold (TRPA1) and cool (TRPM8) receptors in human urogenital organs.2008

    • Author(s)
      Du S, Araki I, Kobayashi H, Zakoji H, Sawada N, Takeda M
    • Journal Title

      Urology 72

      Pages: 450-455

    • Peer Reviewed
  • [Journal Article] Involvement of hypoxia-triggered endoplasmic stress in outlet obstruction-induced apoptosis in the urinary bladder.2008

    • Author(s)
      Sawada N, Yao J, Hayakawa K, Araki I, Takeda M, Kitamura M
    • Journal Title

      Laboratory Investigation 88

      Pages: 553-563

    • Peer Reviewed
  • [Journal Article] Differential impact of lower urinary tract symptoms on geriatric and disease-specific quality of life in men and women.2008

    • Author(s)
      Araki I, Tsuchida T, Nomura T, Fukasawa M, Takihana Y, Koyama Y, Takeda M.
    • Journal Title

      Urologia Internationalis 81

      Pages: 60-65

    • Peer Reviewed
  • [Journal Article]

    • Peer Reviewed
  • [Journal Article]

    • Peer Reviewed
  • [Journal Article]

    • Peer Reviewed
  • [Journal Article]

    • Peer Reviewed
  • [Journal Article]

    • Peer Reviewed
  • [Presentation] GPJ4:Platelet derived growth factor-mediated upregulation of connexin 43 in bladder smooth mscle cells : A possible role in urinary bladder overactivity2010

    • Author(s)
      Norifumi SAWADA, LI Kai, Jian YAO, Hiroshi Nakagomi, Tatsuya Miyamoto, Satoru Kira, Hideki Kobayashi, Takayuki Tsuchida, Masanori KITAMURA, Masayuki Takeda
    • Organizer
      The 5th Pan-PacificContience Society Meeting
    • Place of Presentation
      Korea
    • Year and Date
      2010-09-03
  • [Presentation] The TRPV4 cation channel mediates stretchi-evoked CA2^+ influx and ATP release in primary urothelial cell cultures using original culture cell stretch system2010

    • Author(s)
      Tsutomu Mochizuki, Hiroshi Nakagomi, Tatsuya Miyamoto, Isao Araki, Mitsuharu Yoshiyama, Masayuki Takeda
    • Organizer
      AUA 2010
    • Place of Presentation
      U.S.A.
    • Year and Date
      2010-05-30
  • [Presentation] Symposium : Male LUTS2009

    • Author(s)
      Masayuki Takeda
    • Organizer
      Chairs : The 4th Pan-Pacific Continence Society Meeting
    • Place of Presentation
      Fukuoka
    • Year and Date
      2009-09-10
  • [Presentation] PDGF-mediated regulation of connexin43 expression in bladder smooth muscle cells2009

    • Author(s)
      Norifumi SAWADA, Jian YAO, Nobuhiko HIRAMATSUE, Hideki Kobayashi, Hidenori Zakoji, Tsutomu Mochizuki, Masanori KITAMURA, Isao Araki, Masayuki Takeda
    • Organizer
      The 4th Pan-Pacific Continence Society Meeting
    • Place of Presentation
      Fukuoka
    • Year and Date
      2009-09-10
  • [Presentation] LUTS in 2008 Co-chairs : Masayuki Takeda2008

    • Author(s)
      Masayuki Takeda, Session I.
    • Organizer
      The 3rd Pan-Pacific Continence Society Meeting
    • Place of Presentation
      Taiwan
    • Year and Date
      2008-09-27
  • [Presentation] High incidence of non-detected tumor (pT0) after neoadjuvant endocrine treatment and radical prostatectomy was not correlated with lower incidence of psa recurrence in localized prostatic carcinoma in yamanashi2008

    • Author(s)
      Takashi Yamagishi, Hidenori Zakoji, Mizuya Fukasawa, Teruhisa Nomura, Takayuki Tsuchida, Yoshio Takihana, Isao Araki, Masayuki Takeda
    • Organizer
      Japan
    • Place of Presentation
      U.S.A.
    • Year and Date
      2008-05-20
  • [Presentation] The expression of prostaglandin E2 receptors (EP1, 2, 3, and 4) in the human urinary bladder epithelium of normal and bladder outlet obstruction.2008

    • Author(s)
      Jiang Yuan Jun, Hideki Kobayashi, Norifumi SAWADA, Mitsuharu Yoshiyama, Tsutomu Mochizuki, Hidenori Zakoji, Isao Araki, Masayuki Takeda
    • Organizer
      -A novel mechanism in the E10afferent hyperactivity of bladder-,AUA2008
    • Place of Presentation
      U.S.A.
    • Year and Date
      2008-05-20
  • [Book] Health Publication Ltd2009

    • Author(s)
      C.HFry, A.JKanai, A.Roosen, Masayuki Takeda, D.N.Wood
    • Total Pages
      116-166
    • Publisher
      INCONTINENCE
  • [Remarks] ホームページ等

    • URL

      http://www.uro-yamanashi.com/

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Published: 2012-01-26   Modified: 2016-04-21  

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