Elucidation of pathophysiology in voiding dysfunction after spinal cord injury and its treatments : a study on functional roles of spinal metabotropic glutamatergic mechanism

• Project/Area Number: 19591839
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Urology
• Research Institution: University of Yamanashi
• Principal Investigator: YOSHIYAMA Mitsuharu University of Yamanashi, 大学院・医学工学総合研究部, 医学研究員 (20422694)
• Co-Investigator(Kenkyū-buntansha): KOBAYASHI Hideki 山梨大学, 大学院・医学工学総合研究部, 助教 (50402053)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2007: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
• Keywords: 代謝型グルタミン酸受容体 / 脊髄損傷 / 膀胱 / 外尿道括約筋 / 排尿障害 / マウス

Research Abstract

本研究は、下部尿路機能調節における仙髄代謝型グルタミン酸受容体(mGluR)経路の役割を検討した。mGluR1欠損マウスを用いた研究は、mGluR1が排尿時外尿道括約筋活動に対し抑制性であり、脊損後排尿障害との類似性を示した。mGluR5の薬理実験では、脊損マウスの膀胱収縮時外尿道括約筋活動に対しmGluR5が抑制性に制御することを明らかにした。これらの結果は、脊損後排尿障害の病態にmGluRが深く関わることを示唆する。

Research Products

• [Journal Article] Glutamatergic mechanisms controlling the lower urinary tract function (2009)
  • Author(s): Mitsuharu Yoshiyama
  • Journal Title: LUTS (Lower Urinary Tract Symptoms) (In press)
  • Peer Reviewed
• [Journal Article] Sex differences in expression profile of acid-sensing ion channels in the mouse urinary bladder : a possible involvement in irritative bladder symptoms (2009)
  • Author(s): Hideki Kobayashi
  • Journal Title: BJU International (In press)
  • Peer Reviewed
• [Journal Article] 蓄尿障害(1)排尿筋弛緩-排尿筋過活動抑制 : 抗ムスカリン薬, β3受容体活性薬, BKチャンネル, その他 (2008)
  • Author(s): 芳山充晴
  • Journal Title: 排尿障害プラクティス Vol.16(3) Pages: 9-17
  • Peer Reviewed
• [Journal Article] Sex-related differences in activity of lower urinary tract in response to intravesical acid irritation in decerebrate unanesthetized mice (2008)
  • Author(s): Yoshiyama, M., Kobayashi, H., Araki, I., Du, S., Zakoji, H., and Takeda, M.
  • Journal Title: Am. J. Physiol. Regul. Integr. Comp. Physiol 295 Pages: 954-960
  • Peer Reviewed
• [Journal Article] The role of vasoactive intestinal polypeptide and pituitary adenylate cyclase-activating polypeptide in the neural pathways controlling the lower urinary tract (2008)
  • Author(s): Yoshiyama, M, and de Groat, W.C.
  • Journal Title: J. Mol. Neurosci 36 Pages: 227-240
  • Peer Reviewed
• [Journal Article] Effects of intrathecal administration of pituitary adenylate cyclase activating polypeptide on lower urinary tract functions in rats with intact or transected spinal cords (2008)
  • Author(s): Yoshiyama, M, and de Groat, W.C.
  • Journal Title: Exp. Neurol 211 Pages: 449-455
  • Peer Reviewed
• [Journal Article] Effects of intrathecal administration of pituitary adenylate cyclase activating polypeptide on lower urinary tract functions in rats with intact or transected spinal cords (2008)
  • Author(s): Mitsuharu Yoshiyama
  • Journal Title: Experimental Neurology 211 Pages: 449-455
  • Peer Reviewed
• [Journal Article] Sex-related differences in activity of lower urinary tract in response to intravesical acid irritation in decerebrate unanesthetized mice (2008)
  • Author(s): Mitsuharu Yoshiyama
  • Journal Title: American Journal of Physiology Regulatory Integrative Comparative Physiology 295
  • Peer Reviewed
• [Journal Article] The role of vasoactive intestinal polypeptide and pituitary adenylate cyclase-activating polypeptide in the neural pathways controlling the lower urinary tract (2008)
  • Author(s): Mitsuharu Yoshiyama
  • Journal Title: Journal of Molecular Neuroscience 36 Pages: 227-240
  • Peer Reviewed
• [Journal Article] 蓄尿障害(1)排尿筋弛緩-排尿筋過活動抑制 : 抗ムスカリン薬, β3受容体活性薬, BKチャンネル, その他 (2008)
  • Author(s): 芳山充晴
  • Journal Title: 排尿障害プラクティス 16(3)
• [Journal Article] Effects of intrathecal administration of pituitary adenylate cyclase activating polypeptide on lower urinary tract functions in rats with intact or transected spinal cords. (2008)
  • Author(s): Mitsuharu Yoshiyama
  • Journal Title: Experimental Neurology (In press)
  • Peer Reviewed
• [Journal Article] The role of vasoactive intestinal polypeptide and pituitary adenylate cyclase-activating polypeptide in the neural pathways controlling the lower urinary tract. (2008)
  • Author(s): Mitsuharu Yoshiyama
  • Journal Title: Journal of Molecular Neuroscience (In press)
  • Peer Reviewed
• [Journal Article] Role of spinal metabotropic glutamate receptors in regulation of lower urinary tract function in the decerebrate unanesthetized rat (2007)
  • Author(s): Yoshiyama, M, and de Groat, W.C.
  • Journal Title: Neurosci. Lett. 420 Pages: 18-22
  • Peer Reviewed
• [Journal Article] Transient receptor potential channel A1 involved in sensory transduction of rat urinary bladder through C-fiber pathway (2007)
  • Author(s): Du, S., Araki, I., Yoshiyama, M., Nomura, T., and Takeda, M.
  • Journal Title: Urology 70 Pages: 826-831
  • Peer Reviewed
• [Journal Article] Amiloride-sensitive ion channels in urinary bladder epithelium involved in mechanosensory transduction by modulating stretch-evoked adenosine triphosphate release (2007)
  • Author(s): Du, S., Araki, I., Mikami, Y., Zakoji, H., Beppu, M., Yoshiyama, M., and Takeda, M.
  • Journal Title: Urology 69 Pages: 590-595
  • Peer Reviewed
• [Journal Article] Role of spinal metabotropic glutamate receptors in regulation of lower urinary tract function in the decerebrate unanesthetized rat. (2007)
  • Author(s): Mitsuharu Yoshiyama
  • Journal Title: Neuroscience Letters 420 Pages: 18-22
  • Peer Reviewed
• [Journal Article] Transient receptor potential channel A1 involved in sensory transduction of rat urinary bladder through C-fiber pathway. (2007)
  • Author(s): Shuqi Du
  • Journal Title: Urology 70 Pages: 826-831
  • Peer Reviewed
• [Journal Article] Glutamatergic mechanisms controlling the lower urinary tract function
  • Author(s): Yoshiyama, M.
  • Journal Title: LUTS (Lower Urinary Tract Symptoms) (In press)
  • Peer Reviewed
• [Journal Article] Sex differences in expression profile of acid-sensing ion channels in the mouse urinary bladder : a possible involvement in irritative bladder symptoms
  • Author(s): Kobayashi, H., Yoshiyama, M., Zakoji, H., Takeda, M., and Takeda, M.
  • Journal Title: BJU Int. (In press)
  • Peer Reviewed
• [Presentation] Effects of a metabotropic glutamate receptor subtype 5 antagonist on lower urinary tract functions in mice with normal or transected spinal cords (2008)
  • Author(s): Mitsuharu Yoshiyama
  • Organizer: International Continence Society 38^<th> Annual Meeting
  • Place of Presentation: Cairo, Egypt
  • Year and Date: 2008-10-22
• [Presentation] マウス膀胱内酢酸灌流モデルの性差における酸感受性イオンチャンネルの関与 : 間質性膀胱炎の新しい発症因子として (2008)
  • Author(s): 小林英樹
  • Organizer: 第15回日本排尿機能学会大手町サンケイプラザ
  • Place of Presentation: 東京
  • Year and Date: 2008-09-13
• [Presentation] マウス膀胱内酢酸灌流モデルの性差における酸感受性イオンチャンネルの関与 : 間質性膀胱炎の新しい発症因子として (2008)
  • Author(s): 小林英樹
  • Organizer: 第15回日本排尿機能学会
  • Place of Presentation: 大手町サンケイプラザ、東京
  • Year and Date: 2008-09-13
• [Presentation] ヒト膀胱粘膜におけるTRPV1、TRPV4とTRPA1の発現と下部尿路症状との相関-閉塞と非閉塞の比較- (2008)
  • Author(s): 宮本達也
  • Organizer: 第15回日本排尿機能学会. 大手町サンケイプラザ
  • Place of Presentation: 東京
  • Year and Date: 2008-09-12
• [Presentation] 亜急性期リハビリテーション施行中の尿閉患者に対するバクロフェン、ジスチグミン、αブロッカー3者併用療法の効果 (2008)
  • Author(s): 武田正之
  • Organizer: 第15回日本排尿機能学会大手町サンケイプラザ
  • Place of Presentation: 東京
  • Year and Date: 2008-09-12
• [Presentation] ヒト膀胱粘膜におけるTRPV1、TRPV4とTRPA1の発現と下部尿路症状との相関-閉塞と非閉塞の比較- (2008)
  • Author(s): 宮本達也
  • Organizer: 第15回日本排尿機能学会
  • Place of Presentation: 大手町サンヶイプラザ、東京
  • Year and Date: 2008-09-12
• [Presentation] 亜急性期リハビリテーション施行中の尿閉患者に対するバクロフェン、ジスチグミン、αブロッカー3者併用療法の効果 (2008)
  • Author(s): 武田正之
  • Organizer: 第15回日本排尿機能学会
  • Place of Presentation: 大手町サンケイプラザ、東京
  • Year and Date: 2008-09-12
• [Presentation] 要介護過活動膀胱患者と介護者のQOL向上を目的とした研究-薬物治療単独と社会資源活動の連携介入の併用による治療効果の比較- (2008)
  • Author(s): 小林晴名
  • Organizer: 第15回日本排尿機能学会. 大手町サンケイプラザ
  • Place of Presentation: 東京
  • Year and Date: 2008-09-11
• [Presentation] マウス下部尿路機能に対する代謝型グルタミン酸受容体サブタイプ5拮抗薬の作用 : 脊髄正常群と慢性脊髄損傷群の比較 (2008)
  • Author(s): 芳山充晴
  • Organizer: 第15回日本排尿機能学会. 大手町サンケイプラザ
  • Place of Presentation: 東京
  • Year and Date: 2008-09-11
• [Presentation] マウス下部尿路機能に対する代謝型グルタミン酸受容体サブタイプ5拮抗薬の作用 : 脊髄正常群と慢性脊髄損傷群の比較 (2008)
  • Author(s): 芳山充晴
  • Organizer: 第15回日本排尿機能学会
  • Place of Presentation: 大手町サンケイプラザ、東京
  • Year and Date: 2008-09-11
• [Presentation] 要介護過活動膀胱患者と介護者のQOL向上を目的とした研究-薬物治療単独と社会資源活動の連携介入の併用による治療効果の比較- (2008)
  • Author(s): 小林晴名
  • Organizer: 第15回日本排尿機能学会
  • Place of Presentation: 大手町サンケイプラザ、東京
  • Year and Date: 2008-09-11
• [Presentation] Thr expression of prostaglandin E2 receptors (EP1, 2, 3, and 4) in the human urinary bladder epithelium of normal and bladder outlet obstruction-a novel mechanism in the afferent hyperactivity of bladder (2008)
  • Author(s): Jiang Yuanjun
  • Organizer: American Urological Association Annual Meeting 2008
  • Place of Presentation: Orlando, Florida, U.S.A.
  • Year and Date: 2008-05-20
• [Presentation] Contribution of acid-sensing ion channels to gender difference in mouse bladder response to acetic acid : a novel candidate for interstitial cystitis pathogenesis (2008)
  • Author(s): Hideki Kobayashi
  • Organizer: American Urological Association Annual Meeting 2008
  • Place of Presentation: Orlando, Florida, U.S.A.
  • Year and Date: 2008-05-18
• [Presentation] Effects of a metabotropic glutamate receptor subtype 5 antagonist on lower urinary tract functions in mice with normal or transected spinal cords (2008)
  • Author(s): Yoshiyama, M., Araki, I., Kobayashi, H., Zakoji, H., and Takeda, M.
  • Organizer: International Continence Society 38th Annual Meeting
  • Place of Presentation: Cairo, Egypt
• [Presentation] Involvements of metabotropic glutamate receptor subtype 5 (mGluR5) in control of lower urinary tract in mice with normal or transected spinal cords (2008)
  • Author(s): Yoshiyama, M., Araki, I., Kobayashi, H., Zakoji, H., and Takeda, M.
  • Organizer: The 3rd Pan-Pacific Continence Society Meeting
  • Place of Presentation: Kaohsiung, Taiwan
• [Presentation] Thr expression of prostaglandin E2 receptors (EP1, 2, 3, and 4) in the human urinary bladder epithelium of normal and bladder outlet obstruction - a novel mechanism in the afferent hyperactivity of bladder (2008)
  • Author(s): Yuanjun, J. Kobayashi, H., Sawada, N., Yoshiyama, M., Mochizuki, T., Zakoji, H., Araki, I., and Takeda, M.
  • Organizer: American Urological Association
  • Place of Presentation: Orlando, Florida, U.S.A
• [Presentation] Contribution of acid-sensing ion channels to gender difference in mouse bladder response to acetic acid : a novel candidate for interstitial cystitis pathogenesis (2008)
  • Author(s): Kobayashi, H., Yoshiyama, M., Araki, I., Zakoji, H., Sawada, N., Mochizuki, T., Tsuchida, T., Nomura, T., Fukasawa, M., and Takeda, M.
  • Organizer: American Urological Association May
  • Place of Presentation: Orlando, Florida, U.S.A
• [Presentation] 膀胱求心路の機械的知覚伝達における代謝型グルタミン酸受容体サブタイプmGluR1とmGluR5を介する相加的コントロール (2007)
  • Author(s): 芳山充晴
  • Organizer: 第14回日本排尿機能学会
  • Place of Presentation: 福島県ホテルリステル猪苗代
  • Year and Date: 2007-10-06
• [Presentation] 膀胱炎モデル(マウス)における酸感受性イオンチャンネルの発現量変化 (2007)
  • Author(s): 小林英樹
  • Organizer: 第14回日本排尿機能学会
  • Place of Presentation: 福島県ホテルリステル猪苗代
  • Year and Date: 2007-10-06
• [Presentation] 膀胱求心路の機械的知覚伝達における代謝型グルタミン酸受容体サブタイプmGluR1とmGluR5を介する相加的コントロール (2007)
  • Author(s): 芳山 充晴
  • Organizer: 第14回 日本排尿機能学会
  • Place of Presentation: 福島県ホテルリステル猪苗代
  • Year and Date: 2007-10-06
• [Presentation] 膀胱炎モデル(マウス)における酸感受性イオンチャンネルの発現量変化 (2007)
  • Author(s): 小林 英樹
  • Organizer: 第14回 日本排尿機能学会
  • Place of Presentation: 福島県ホテルリステル猪苗代
  • Year and Date: 2007-10-06
• [Presentation] 大コンダクタンスCa感受性Kチャネル(BKチャネル)のヒトとラットの膀胱における発現と機能の検討 (2007)
  • Author(s): 座光寺秀典
  • Organizer: 第14回日本排尿機能学会
  • Place of Presentation: 福島県ホテルリステル猪苗代
  • Year and Date: 2007-10-05
• [Presentation] ヒト下部尿路閉塞膀胱上皮におけるProstaglandin E2受容体サブタイプ(EP1, EP2, EP3, EP4)の発現 (2007)
  • Author(s): 姜元軍
  • Organizer: 第14回日本排尿機能学会
  • Place of Presentation: 福島県ホテルリステル猪苗代
  • Year and Date: 2007-10-05
• [Presentation] 大コンダクタンスCa感受性Kチャネル(BKチャネル)のヒトとラットの膀胱における発現と機能の検討 (2007)
  • Author(s): 座光寺 秀典
  • Organizer: 第14回 日本排尿機能学会
  • Place of Presentation: 福島県ホテルリステル猪苗代
  • Year and Date: 2007-10-05
• [Presentation] ヒト下部尿路閉塞膀胱上皮におけるProstaglandin E2受容体サブタイプ(EP1,EP2,EP3,EP4)の発現 (2007)
  • Author(s): 姜 元軍
  • Organizer: 第14回 日本排尿機能学会
  • Place of Presentation: 福島県ホテルリステル猪苗代
  • Year and Date: 2007-10-05
• [Presentation] Irradiation induces detrusor overactivity-studied acutely using a mouse model of radiation cystitis. (2007)
  • Author(s): Irina Zabbarova
  • Organizer: International Continence Society 37th Annual Meeting
  • Place of Presentation: Rotterdam, The Netherlands
  • Year and Date: 2007-08-23
• [Presentation] Acid-sensing ion channel: expression changes in the urinary bladder following chronic bladder inflammation. (2007)
  • Author(s): Hideki Kobayashi
  • Organizer: International Continence Society 37th Annual Meeting
  • Place of Presentation: Rotterdam, The Netherlands
  • Year and Date: 2007-08-22
• [Presentation] The expression and the role of BK channels in the urinary bladder: the alteration of subunit expression profile in association with bladder outlet obstruction, and the affect of BK channel on afferent pathway in lower urinary tract. (2007)
  • Author(s): Hidenori Zakoji
  • Organizer: International Continence Society 37th Annual Meeting
  • Place of Presentation: Rotterdam, The Netherlands
  • Year and Date: 2007-08-22
• [Presentation] Additive control by metabotropic glutamate receptors 1 and 5 in bladder afferent mechanosensory transmission. (2007)
  • Author(s): Mitsuharu Yoshiyama
  • Organizer: International Continence Society 37th Annual Meeting
  • Place of Presentation: Rotterdam, The Netherlands
  • Year and Date: 2007-08-22
• [Presentation] The expression and role of large conductance, voltage-and Ca^2+-activated K^+(BK)channels in the urinary bladder: the alteration of subunit expressionprofile in association with bladder outlet obstruction, and the affect of BK channel on the afferent ex. (2007)
  • Author(s): Hidenori Zakoji
  • Organizer: American Urological Association
  • Place of Presentation: Anaheim, California, USA
  • Year and Date: 2007-05-21
• [Presentation] Amiloride-sensitive ion channels in urinary bladder epithelium involved in mechanosensory transduction by modulating stretch-evoked ATP release. (2007)
  • Author(s): Shuqi Du
  • Organizer: American Urological Association
  • Place of Presentation: Anaheim, California, USA
  • Year and Date: 2007-05-21
• [Presentation] Agonists of transient receptor potential channel A1 cause hyper-reflexic micturition by affecting bladder afferent activity in rats. (2007)
  • Author(s): Shuqi Du
  • Organizer: American Urological Association
  • Place of Presentation: Anaheim, California, USA
  • Year and Date: 2007-05-21
• [Presentation] Role of metabotropic glutamate receptor subtype 1 in afferent processing of reflex micturition in mice. (2007)
  • Author(s): Mitsuharu Yoshiyama
  • Organizer: American Urological Association
  • Place of Presentation: Anaheim, California, USA
  • Year and Date: 2007-05-20
• [Presentation] Irradiation induces detrusor overactivity studied acutely using a mouse model of radiation cystitis (2007)
  • Author(s): Zabbarova, I., Roppolo, J., Yoshiyama, M., Ikeda, Y., McCarthy, C., Hagedorn, N., Birder, L., Fry, C., de Groat, W., and Kanai, A
  • Organizer: International Continence Society 37^<th> Annual Meeting
  • Place of Presentation: Rotterdam, The Netherlands
• [Presentation] Acid-sensing ion channel : expression changes in the urinary bladder following chronic bladder inflammation (2007)
  • Author(s): Kobayashi, H., Araki, I., Zakoji, H., Du, S., Sawada, N., Mochizuki, T., Yoshiyama, M., Tsuchida, T., Nomura, T., Fukasawa, M., Takihana, Y., and Takeda, M.
  • Organizer: International Continence Society 37^<th> Annual Meeting, Rotterdam
  • Place of Presentation: The Netherlands
• [Presentation] The expression and the role of BK channels in the urinary bladder : the alteration of subunit expression profile in association with bladder outlet obstruction, and the affect of BK channel on afferent pathway in lower urinary tract (2007)
  • Author(s): Zakoji, H., Araki, I., Beppu, M., Yoshiyama, M., Du, S., Kobayashi, H., Mochizuki, T., and Takeda, M.
  • Organizer: International Continence Society 37^<th> Annual Meeting, Rotterdam
  • Place of Presentation: The Netherlands
• [Presentation] Additive control by metabotropic glutamate receptors 1 and 5 in bladder afferent mechanosensory transmission (2007)
  • Author(s): Yoshiyama, M., Araki, I., Zakoji, H., Kobayashi, H., Du, S., Aiba, A., and Takeda, M.
  • Organizer: International Continence Society 37^<th> Annual Meeting
  • Place of Presentation: Rotterdam, The Netherlands
• [Presentation] Photo-stimulating effects of low reactive level laser on micturition function in rats (2007)
  • Author(s): Uchiyama, T., Sakakibara, R., Yoshiyama, M., Lui, Z., Yamamoto, T., Ito, T., Yamaguchi, C, Awa, Y., Yamanishi, T., and Hattori, T.
  • Organizer: International Continence Society 37^<th> Annual Meeting
  • Place of Presentation: Rotterdam, The Netherlands
• [Presentation] Different cystometric responses between male and female mice to the lower urinary tract irritation by acetic acid (2007)
  • Author(s): Yoshiyama, M., Araki, I., Kobayashi, H., Zakoji, H., Du, S., and Takeda, M.
  • Organizer: International Continence Society 37^<th> Annual Meeting
  • Place of Presentation: Rotterdam, The Netherlands
• [Presentation] Role of metabotropic glutamate receptor subtype 1 in afferent processing of reflex micturition in mice (2007)
  • Author(s): Yoshiyama, M., Araki, I., Zakoji, H. Kobayashi, H., Du, S., Aiba, A., and Takeda, M.
  • Organizer: American Urological Association
  • Place of Presentation: Anaheim, California, U.S.A.
• [Presentation] The expression and role of large conductance, voltage- and Ca^<2+>-activated K^+ (BK) channels in the urinary bladder : the alteration of subunit expression profile in association with bladder outlet obstruction, and the affect of BK channel on the afferent ex (2007)
  • Author(s): Zakoji, H., Araki, I., Beppu, M., Yoshiyama, M., Kobayashi, H., Du, S., Sawada, N., Mochizuki, T., Fukasawa, M., Takihana, Y., and Takeda, M.
  • Organizer: American Urological Association
  • Place of Presentation: Anaheim, California, U.S.A.
• [Presentation] Amiloride-sensitive ion channels in urinary bladder epithelium involved in mechanosensory transduction by modulating stretch-evoked ATP release (2007)
  • Author(s): Du, S., Araki, I., Mikami, Y., Yoshiyama, M., and Takeda, M.
  • Organizer: American Urological Association
  • Place of Presentation: Anaheim, California, U.S.A.
• [Presentation] Agonists of transient receptor potential channel A1 cause hyper-reflexic micturition by affecting bladder afferent activity in rats (2007)
  • Author(s): Du, S., Araki, I., Nomura, T., Yoshiyama, M., and Takeda, M.
  • Organizer: American Urological Association
  • Place of Presentation: Anaheim, California, U.S.A.