The elucidation of ATP releasing pathway of bladder epithelial cell upon stretch stimulation

• Project/Area Number: 23791749
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: University of Yamanashi
• Principal Investigator: NAKAGOMI Hiroshi 山梨大学, 医学部附属病院, 助教 (80418714)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: シグナル伝達 / 生理学 / 神経科学 / 国際情報交換 / 国際情報交流

Research Abstract

We have investigated exocytotic release of ATP from urothelium, especially focusing on vesicular nucleotide transporter (VNUT). VNUT gene and protein was highly expressed in the epithelial layer of mouse bladder tissue and primary urothelial cell culture. The stretch-evoked ATP release was significantly reduced by the treatment of VNUT siRNA or several inhibitors of vesicular exocytosis. These findings suggest that VNUT plays an important role in stretch-elicited ATP release from urothelium.

Research Products

• [Journal Article] 医薬ジャーナル (2013)
  • Author(s): 武田正之、荒木勇雄、澤田智史、中込宙史、望月勉、小林英樹、座光寺秀典、芳山充晴
  • Journal Title: 新薬展望 2013 Volume: Vol. 49
• [Journal Article] 排尿障害におけるβ3 受容体刺激(作 動)薬 (2012)
  • Author(s): 武田正之、中込宙史、芳山充晴、荒木勇雄
  • Journal Title: 診断と治療 Volume: 第100巻・第8号 Pages: 1379-1385
• [Journal Article] 排尿障害におけるβ3 受容体作動薬 (2012)
  • Author(s): 武田正之、中込宙史、芳山充晴、荒木勇雄
  • Journal Title: Progress in Medicine Volume: Vol. 32 (No. 4) Pages: 37-42
• [Journal Article] 第4回国際尿失禁会議からの報告 (2011)
  • Author(s): 武田正之、中込宙史、宮本達也、吉良聡、芳山充晴
  • Journal Title: Committee3 Cell Biology 「細胞生物学」.排尿障害プラクティス Volume: Vol.19(1) Pages: 66-88
• [Journal Article] Sensor mechanism and afferent signal transduction of the urinary bladder: special focus on transient receptor potential ion channels (2010)
  • Author(s): Takeda M, Mochizuki T, Yoshiyama M, Nakagomi H, Kobayashi H, Sawada N, Zakohji H, Du S, Araki I
  • Journal Title: LUTS (Lower Urinary Tract Symptoms) Volume: 2 Pages: 51-60
  • Peer Reviewed
• [Journal Article] 尿路上皮と排尿 (2010)
  • Author(s): 荒木勇雄、中込宙史、望月勉、小林英樹、芳山充晴、武田正之
  • Journal Title: 臨床検査 Volume: Vol.54(7) Pages: 726-730
• [Presentation] VNUT plays a crucial role in stretch-evoked ATP releasefrom urothelium (2013)
  • Author(s): 中込 宙史
  • Organizer: アメリカ泌尿器科学会
  • Place of Presentation: Georgia World Congress Center(Atlanta USA)
• [Presentation] ヒト膀胱上皮における VNUT m-RNA発現量と各種排尿パラメータとの関連性 (2013)
  • Author(s): 中込 宙史
  • Organizer: 日本泌尿器科学会総会
  • Place of Presentation: さっぽろ芸術文化の館（北海道）
• [Presentation] 代謝型グルタミン酸受容体サブタイプ5 を介する神経伝達の遮断は膀胱収縮性及び排尿を損ねずに蓄尿を促す (2012)
  • Author(s): 芳山充晴、土屋幸子、望月勉、中込宙史、宮本達也、吉良聡、武田正之
  • Organizer: 第19回日本排尿機能学会
  • Place of Presentation: 愛知県名古屋市・名古屋国際会議場
  • Year and Date: 2012-08-30
• [Presentation] Vesicular nucleotide transporter (VNUT) is a key molecule for mechanosensing in the human urinary bladder: negative correlation between VNUT expression in human bladder mucosa and first desire to void (2012)
  • Author(s): Nakagomi H, Mochizuki T, Miyamoto T, Kira S, Yoshiyama M, Kawahara K, Moriyama Y, Koizumi S, Takeda M
  • Organizer: (Abstract No. 12) International Continence Society 42nd Annual meeting, China National Convention Centre
  • Place of Presentation: Beijing, China
• [Presentation] VNUT (vesicular nucleotide transporter) plays a crucial role in stretch-evoked ATP release from urothelium (2012)
  • Author(s): Nakagomi H, Mochizuki T, Miyamoto T, Yoshiyama M, Araki I, Moriyama Y, Koizumi S, Takeda M
  • Organizer: (Abstract No. 495, May 20, 2012) American Urological Association Annual Meeting, Georgia World Congress Center
  • Place of Presentation: Atlanta, Georgia, U.S.A
• [Presentation] Evaluation of increased voiding frequency in mice with type 2 diabetes mellitus (2012)
  • Author(s): Yoshiyama M, Mochizuki T, Nakagomi H, Miyamoto T, Takeda M
  • Organizer: (Abstract No. 256, May 20, 2012) American Urological Association Annual Meeting
  • Place of Presentation: Georgia World Congress Center, Atlanta, Georgia, U.S.A.
• [Presentation] 伸展刺激時の膀胱上皮からのATP放出機構におけるVNUT／開口放出経路の解析 (2012)
  • Author(s): 中込 宙史
  • Organizer: 日本泌尿器科学会総会
  • Place of Presentation: パシフィコ横浜（神奈川）
• [Presentation] The relations between the expression Vesicular Nucleotide Transporter ( VNUT ) in the human bladder mucosa and urological clinical parameters. (2012)
  • Author(s): 武田 正之
  • Organizer: 国際尿禁制学会
  • Place of Presentation: 中国国際会議場（北京 中国）
• [Presentation] 伸展刺激に対する膀胱上皮細胞からのＡＴＰ放出メカニズム (2012)
  • Author(s): 中込宙史
  • Organizer: 第85回日本薬理学会
  • Place of Presentation: 国立京都国際会館（京都）
• [Presentation] 新規のマウス用排尿代謝ケージ構築ならびに各種パラメーターについて～野生型マウスとTRPV4 ノックアウトマウスとの比較～ (2011)
  • Author(s): 望月勉,中込宙史,芳山充晴,高山靖規,富永真琴,水町凉治,武田正之
  • Organizer: 第18回日本排尿機能学会
  • Place of Presentation: 福井県福井市
• [Presentation] 遺伝性発症2 型糖尿病マウスの若年期における頻尿の病態解析 (2011)
  • Author(s): 芳山充晴,望月勉,中込宙史,宮本達也,武田正之
  • Organizer: 第18回日本排尿機能学会
  • Place of Presentation: 福井県福井市
• [Presentation] VNUT (Vesicular Nucleotide Transporter) を介する膀胱上皮からの ATP 放出メカニズムの解明 (2011)
  • Author(s): 中込宙史,望月勉,芳山充晴,宮本達也,吉良聡,川原和也,荒木勇雄,小泉修一,森山芳則,武田正之
  • Organizer: 第18回日本排尿機能学会
  • Place of Presentation: 福井県福井市
• [Presentation] Comparisons between voluntary behaviour and reflex response in control of the lower urinary tract function of mice (2011)
  • Author(s): Yoshiyama M, Mochizuki T, Nakagomi H, Kobayashi H, Miyamoto T, Zakoji H, Takeda M
  • Organizer: (Abstract No. 453) International Continence Society Meeting 41st
  • Place of Presentation: Glasgow, U.K.
• [Presentation] TRPV4-deficient mice exhibit increased frequency of voiding ~evaluation of micturition behaviour using novel metabolic cage system (2011)
  • Author(s): Mochizuki T, Yoshiyama M, Nakagomi H, Miyamoto T, Takeda M
  • Organizer: (Abstract No. 411) International Continence Society Meeting 41st
  • Place of Presentation: Glasgow, U.K.
• [Presentation] Risk factors of nocturia and assessment of nocturia-related quality of life in Japanese population (2011)
  • Author(s): Imamura N, Yoda Y, Nakagomi H, Miyamoto T, Tsuchida T, Fukazawa M, Araki I, Yoshiyama M, Takeda M
  • Organizer: (Abstract No. 375) International Continence Society Meeting 41st
  • Place of Presentation: Glasgow, U.K.
• [Presentation] VNUT plays an important role in vesicular storage and subsequent exocytosis of ATP from bladder epithelium upon mechanical stretch stimulation (2011)
  • Author(s): Nakagomi H, Mochizuki T, Miyamoto T, Kira S, Yoshiyama M, Araki I, Koizumi S, Moriyama Y, Takeda M
  • Organizer: (Abstract No. 278) International Continence Society Meeting 41st
  • Place of Presentation: Glasgow, U.K.
• [Presentation] Evalutations of increased voiding frequency in mice with diabetes mellitus at early stage (2011)
  • Author(s): Yoshiyama M, Mochizuki T, Nakagomi H, Miyamoto T, Kobayashi H, Zakoji H, Takeda M
  • Organizer: (Abstract No. 182) International Continence Society Meeting 41st
  • Place of Presentation: Glasgow, U.K.
• [Presentation] 膀胱上皮細胞の伸展刺激に対するＡＴＰ放出メカニズムの解明 (2011)
  • Author(s): 中込宙史
  • Organizer: 第99回日本泌尿器科学会総会
  • Place of Presentation: 名古屋国際会議場（名古屋）
• [Presentation] 膀胱上皮のＴＲＰＶチャネルとＡＴＰ放出メカニズム (2011)
  • Author(s): 中込宙史
  • Organizer: 第99回日本泌尿器科学会総会(招待講演)
  • Place of Presentation: 名古屋国際会議場（名古屋）
• [Presentation] VNUT(Vesicular Nucleotide Transporter)を介する膀胱上皮からのATP放出メカニズムの解明 (2011)
  • Author(s): 中込宙史
  • Organizer: 第18回日本排尿機能学会
  • Place of Presentation: 福井フェニックスプラザ（福井）
• [Presentation] VNUT PLAYS AN IMPORTANT ROLE IN VESICULAR STORAGE AND SUBSEQUENT EXOCYTOSIS OF ATP FROM BLADDER EPITHELIUM UPON MECHANICAL STRETCH STIMULATION (2011)
  • Author(s): Hiroshi Nakagomi
  • Organizer: 41st ANNUAL MEETING OF THE INTERNATIONAL CONTINENCE SOCIETY (ICS)
  • Place of Presentation: ScotishiExhibition&conference Center（Glasgow,UK）
• [Presentation] 新規ディバイス排尿用代謝ケージを用いたマウス排尿測定～野生型マウスの各種排尿パラメーターにおける雌雄差について (2010)
  • Author(s): 望月勉,中込宙史,芳山充晴,水町凉治,武田正之
  • Organizer: 第17回日本排尿機能学会
  • Place of Presentation: 山梨県甲府市
• [Presentation] Gene expression patterns of acid-sensing ion channels (ASICs) families in mammalian bladder (2010)
  • Author(s): Kobayashi H, Yoshiyama M, Inuzuka H, Kira S, Nakagomi H, Miyamoto T, Haneda Y, Sawada N, Zakoji H, Tsuchida T, Araki I, Takeda M
  • Organizer: (Abstract No. 520) International Continence Society 40th/International Uro-Gynecology Association Joint Meeting
  • Place of Presentation: Toronto, Canada
• [Presentation] Hypertension and type 2 diabetes mellitus are highly associated with nocturia than metabolic syndrome in Japanese population (2010)
  • Author(s): Imamura N, Nakagomi H, Yoda Y, Zakoji H, Kobayashi H, Tsuchida T, Fukazawa M, Yoshiyama M, Araki I, Takeda M
  • Organizer: (Abstract No. 381) International Continence Society 40th /International Uro-Gynecology Association Joint Meeting
  • Place of Presentation: Toronto, Canada
• [Remarks] なし