2005 Fiscal Year Final Research Report Summary
Development of new drugs targeting at the urothelial-afferent neurotransduction system for bladder storage dysfunction
| Project/Area Number |
16591589
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | SHINSHU UNIVERSITY |
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Principal Investigator |
IGAWA Yasuhiko Shinshu Univ., Sch.of Med., Dept.of Urology, Associate Professor, 医学部・泌尿器科学講座, 助教授 (40159588)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIZUKA Osamu Shinshu Univ., Sch.of Med., Dept.of Urology, Associate Professor, 医学部・泌尿器科学講座, 助教授 (20184541)
SEKI Satoshi Shinshu Univ., Shinshu Univ.hosp., Dept.of Urology, Assistant Professor, 医学部附属病院・泌尿器科, 助手 (60293502)
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| Project Period (FY) |
2004 – 2005
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| Keywords | interstitial cystitis / detrusor overactivity / bladder sensation / resiniferatoxin / urothelium / afferent neurotransduction / P2X3受容体 / 求心性神経伝達 |
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| Research Abstract |
1) In conscious rats, intravesical instillation of TNP-ATP, an antagonist for P2X3 receptors, dose-dependently increased bladder capacity and threshold pressure for voiding. On the other hand, ATP, an agonist for P2X receptors, decreased these two parameters, and pretreatment with TNP-ATP blocked the effect of ATP. Theses results suggest that activation of P2X3 receptors facilitates the urothelial-afferent neurotransduction system in the rat bladder.
2) The physiological role of muscarinic M2 and M3 receptors in the lower urinary tract function was investigated in a conscious cystometric study by using M2 or M3 knockout mice. It is concluded that M3 receptor is the principal muscarinic receptor subtype responsible for voiding bladder contractions, and the role of M2 receptors is of minor importance (ref. 1).
3) The threshold for intravesical urothelial electric stimulation with three different frequencies was investigated in 9 patients with benign prostatic hyperplasia (BPH) and 5 with i
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nterstitial cystitis (IC). We found that the threshold values, with all three frequencies, in IC group was significantly lower that those in BPH group. Intravesical instillation of a local anesthetic (0.5% bupivacain) increased the threshold in all 4 IC patients tested.
4) The clinical and urodynamic effects of intravesical instillation of resiniferatoxin (RTX, 1〓M) were investigated in 5 patients with detrusor overactivity (DO) and 6 patients with interstitial cystitis (IC) resistant against standard conservative therapy. Four of 5 DO patients responded to the treatment within 1 week after the instillation, and the effect lasted for 3-9 months. In the IC group, all 6 patients showed improvement of their storage symptoms within 1 week after the treatment, and bladder pain score and mean voided volume were significantly improved. However, these effects disappeared within 2-3 months. No adverse events were reported.
5) All together, the results of the present study indicate that urothelial-afferent neurotransduction system is a promising therapeutic targets in the treatment of intractable bladder storage disorders, such as DO and IC. Less
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Research Products
(2 results)
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[Journal Article] Cystometric findings in mice lacking muscarinic M_2 or M_3 receptors.2004
Author(s)
Igawa Y, Zhang X, Nishizawa O, Umeda M, Iwata A, Taketo MM, Manabe T, Matsui, M, Andersson KE
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Journal Title
J Urol. 172(6, Part 1 of 2)
Pages: 2460-2464
Description
「研究成果報告書概要(欧文)」より
