Functional analysis of the metabotropic glutamate receptor and the acid-sensitive ion channels as a urine collection control molecule
Project/Area Number |
16K11042
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Urology
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Research Institution | University of Yamanashi |
Principal Investigator |
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Research Collaborator |
IHARA Tatsuya
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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Keywords | マウス / 代謝型グルタミン酸受容体 / 酸感受性イオンチャンネル / 下部尿路機能 / 膀胱 / 尿道 / 中枢神経 / 末梢神経 / 酸感受性チャネル / 膀胱過活動 / 求心路 / 蓄尿障害 / 外尿道括約筋 / 興奮性グルタミン酸受容体 / 酸感受性イオンチャネル / 排尿機能学 |
Outline of Final Research Achievements |
The study using metabotropic glutamate receptor subtype 1 (mGluR1) gene deficit (KO) mice and mGluR5 antagonist revealed that mGluR1 and mGluR5 are involved in excitatory afferent signal transmission from the bladder in control of lower urinary tract (LUT) function and that the mGluR phenotype has a sex difference in the LUT function. Moreover, another study showed that acid-sensing ion channels (ASICs) are associated with excitatory afferent signal transduction in acid-induced bladder hyperreflexia as well as normal bladder activity. The present studies show that mGluR1, mGluR5 and ASICs can be target molecules for development of pharmacotherapy of lower urinary tract dysfunction such as bladder overactivity and thus these results would contribute to ameliorating a quality of life of patients who suffer from such dysfunction and to improving social productivity.
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Academic Significance and Societal Importance of the Research Achievements |
膀胱過活動症状はヒトの日常生活の質と生産活動性を著しく低下させる。故に、その発症機構の解明と治療法の開発は、同症状による損失を回避する上で重要である。本研究は、膀胱からの興奮性求心性信号伝達に代謝型グルタミン酸受容体(mGluR)と酸感受性イオンチャネル(ASICs)が関与することを解明した。一方、このmGluR関与の程度には雌雄差があることも明らかにした。この結果は、標的分子の表現型に性差がある可能性を念頭に研究を実施するべきであることを示唆する。近年、医学研究において、遺伝子関連の表現型や薬物療法への反応性に性別を考慮することの重要性が提唱されており、本研究結果はそれに同調する。
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Report
(4 results)
Research Products
(38 results)
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[Journal Article] Role of proNGF/p75 signaling in bladder dysfunction after spinal cord injury2018
Author(s)
Ryu Jae Cheon、Tooke Katharine、Malley Susan E.、Soulas Anastasia、Weiss Tirzah、Ganesh Nisha、Saidi Nabila、Daugherty Stephanie、Saragovi Uri、Ikeda Youko、Zabbarova Irina、Kanai Anthony J.、Yoshiyama Mitsuharu、Farhadi H. Francis、de Groat William C.、Vizzard Margaret A.、Yoon Sung Ok
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Journal Title
Journal of Clinical Investigation
Volume: 128
Issue: 5
Pages: 1772-1786
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] The time-dependent variation of ATP release in mouse primary cultured urothelial cells is regulated by the Clock gene.2018
Author(s)
Ihara T, Mitsui T, Nakamura Y, Kanda M, Tsuchiya S, Kira S, Nakagomi H, Sawada N, Kamiyama M, Hirayama Y, Shigetomi E, Shinozaki Y, Yoshiyama M, Nakao A, Takeda M Koizumi S
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Journal Title
Neurourology and urodynamics
Volume: 37
Issue: 8
Pages: 2535-2543
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Clock Genes Regulate the Circadian Expression of Piezo1, TRPV4, Connexin26, and VNUT in an Ex Vivo Mouse Bladder Mucosa.2017
Author(s)
5.Ihara T, Mitsui T, Nakamura Y, Kira S, Nakagomi H, Sawada N, Hirayama Y, Shibata K, Shigetomi E, Shinozaki Y, Yoshiyama M, Andersson KE, Nakao A, Takeda M, Koizumi S
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Journal Title
PLoS One
Volume: 12
Issue: 1
Pages: e0168234-e0168234
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Urothelial ATP exocytosis: regulation of bladder compliance in the urine storage phase2016
Author(s)
Nakagomi H,Yoshiyama M,Mochizuki T,Miyamoto T,Komatsu R,Imura Y,Morizawa Y,Hiasa M,Kira S,Fujishita K,Shibata K,Shigetomi E,Shinozaki Y,Takeda M,Koizumi S
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Journal Title
Scientific Reports
Volume: 6
Issue: 1
Pages: 29761-29761
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Netupitant, a potent and highly selective NK1 receptor antagonist, alleviates acetic acid-induced bladder overactivity in anesthetized guinea-pigs2016
Author(s)
Palea S, Guilloteau V, Rekik M, Lovati E, Guerard M, Guardia MA, Lluel P, Pietra C, Yoshiyama M
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Journal Title
Frontiers in Pharmacology
Volume: 7
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] The Clock mutant mouse is a novel experimental model for nocturia and nocturnal polyuria.2016
Author(s)
Ihara, T., Mitsui, T., Nakamura, Y., Kira, S., Miyamoto, T., Nakagomi, H., Sawada, N., Hirayama, Y., Shibata, K., Shigetomi, E., Shinozaki, Y., Yoshiyama, M., Nakao, A., *Takeda, M. *Koizumi, S.
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Journal Title
Neurourology and Urodynamics
Volume: 36
Issue: 4
Pages: 1034-1038
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Effect of restraint stress on alternation of circadian bladder function to induce nocturia2017
Author(s)
T Ihara,Y Nakamura,T Mitsui,Y Otake,Y Imai,S Kira,H Nakagomi,N Sawada,M Yoshiyama,S Koizumi,A Nakao,M Takeda
Organizer
International Continence Society 47th Annual meeting
Related Report
Int'l Joint Research
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[Presentation] Circadian regulations of Piezo1, TRPV4, Connexin26 and VNUT by clock genes in the mouse bladder urothelium2016
Author(s)
Ihara T, Nakamura Y, Mitsui T, Kira S, Nakagomi H, Sawada N, Shinozaki Y, Yoshiyama M, Nakao A, Takeda M, Koizumi S
Organizer
International Continence Society 46th Annual meeting
Place of Presentation
東京国際フォーラム(東京都千代田区)
Year and Date
2016-09-15
Related Report
Int'l Joint Research
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[Presentation] Clock genes regulate circadian rhythm of VNUT expression,Connexin26 expression and stretch-evoked ATP release in the cultured urothelial cells2016
Author(s)
Ihara T, Kira S, Miyamoto T, Sawada N, Nakagomi H, Mitsui T, Kobayashi H, Yoshiyama M, Takeda M, Nakamura Y, Nakao A, Shigetomi E, Shinozaki Y, Koizumi S
Organizer
American Urological Association Annual Meeting
Place of Presentation
San Diego, California, U.S.A.
Year and Date
2016-05-09
Related Report
Int'l Joint Research
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