2002 Fiscal Year Final Research Report Summary
Development of new drugs for bladder storage dysfunction targeting beta3 adrenoceptors and bladder afferent nerves
| Project/Area Number |
13671641
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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, SCHOOL OF MEDICINE |
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Principal Investigator |
IGAWA Yasuhiko Shinshu Univ. Sch. Of Med., Dept. of Urology, Associate Professor, 医学部, 助教授 (40159588)
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| Co-Investigator(Kenkyū-buntansha) |
SATOH Tomoya Shinshu Univ. Sch. Of Med., Dept. of Urology, Assistant Professor, 医学部附属病院, 助手 (30291272)
ISHIZUKA Osamu Shinshu Univ. Sch. Of Med., Dept. of Urology, Associate Professor, 医学部, 助教授 (20184541)
NISHIZAWA Osamu Shinshu Univ. Sch. Of Med., Dept. of Urology, Professor, 医学部, 教授 (60091815)
KOBAYASHI Shinya Shinshu Univ. Hosp., Dept. of Urology, Assistant Professor, 医学部附属病院, 助手 (20303472)
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| Project Period (FY) |
2001 – 2002
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| Keywords | β3 adrepceptors / afferent nerves / overactive bladder / P2X3 receptors / capsaicin / resiniferatoxin / レジニフェラトキシン |
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| Research Abstract |
(1) The relaxant response to adrenergic stimulation in the human normal detrusor was found to be mediated mainly through β3-adrenoceptors (β3-Ars)^1. This was true also in neurogenic (both hyper reflexic and low-compliant) bladders^1. A selective β3-AR agonist, CL316243 surppressed bladder overactivity induced by intravesical instillation of prostaglandin E2 in conscious rats^2 and bladder overactivity in cerebral infarcted rats^3 without increasing post-residual volume and without significant cardiovascular side effects. These results suggest that selective β3-AR agonists may be used for the treatment of overactive bladder.
(2) Intravesical instillation of ATP (0.1-10 mM) caused bladder overactivity in conscious rats. Intravesical instillation of TNP-ATP (0.5-5.0 μM), a P2X_<2/3> antagonist, increased voiding intervals, bladder capacity and micturition volumes and counteracted the ATP-induced overactivity, suggesting increased extracellular ATP has a role in mechanoafferent transduction in the rat bladder though P2X_<2/3> receptors
(3) The clinical and urodynamic effects of intravesical instillation of capsaicin (2 mM, 100 ml) in 7 spinal cord injured patients with detrusor hyperreflexia and autonomic dysreflexia, and of resiniferatoxin (RTX, IνM, 100 ml) in 4 patients with overactive bladder (OAB) and 5 patients with interstitial cystitis (IC), were inverstigated. Capsaicin improved both reflexic urinary incontinence and symptoms related to autonomic dysreflexia in all the 7 patients^4. After RTX treatment, 3 of 4 with OAB and 4 of 5 with IC showed symptomatic improvement. The beneficial effect emerged more quickly after RTX treatment than after capsaicin, and lasted for at least 3 months after either of the two drugs. No adverse effects were found.
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