| Project/Area Number |
18590237
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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 |
General pharmacology
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| Research Institution | University of Shizuoka |
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Principal Investigator |
YAMADA Shizuo University of Shizuoka, School of Pharmaceutical Sciences, Pharmacokinetics and Pharmacodynamis, Professor (80106434)
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| Co-Investigator(Kenkyū-buntansha) |
OKI Tomomi University of Shizuoka, School of Pharmaceutical Sciences, Pharmacokinetics and Pharmacodynamis, Research associate (50405148)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,080,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Benign urostatic hvnernlasia / Overactive bladder / Urinary bladder / Neurotransmitter receptors / Cerebral infarction / Bladder outlet obstruction / Interstitial / 尿道部分閉塞 / 間質性膀胱炎 / 膀胱 / ムスカリン性受容体 / アンギオテンシン受容体 / ATP受容体 / 受容体拮抗薬 / 脊髄損傷 / 脳梗塞 / 尿道閉塞 / 膀胱ムスカリン性受容体 / 抗コリン薬 |
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| Research Abstract |
The aim of this study is to characterize bladder neurotransmitter receptor binding and urodynamic parameters in rats with cerebral infarction, chronic bladder outlet obstruction, cyclophosphamide (CYP) and HCl-treated rats as models of urinary dysfunction due to benign prostatic hyperplasia (BPH) , overactive bladder (OAB) and interstitial cystitis (IC).
1) Bladder capacity and voided volume were significantly lower in the cerebral-infarcted than in the sham rats. Involuntary contractions before micturition were seen in the bladder outlet-obstructed rats but not in sham rats. The cerebral infarction but not bladder outlet obstruction in rats caused up-regulation of bladder muscarinic receptors, and that such regulation of bladder muscarinic receptors may be at least partly associated with the symptoms of detrusor overactivity subsequent to cerebral infarction.
2) In the cystometry of CYP-treated rats compared with control rats, the micturition interval and micturition volume were signifi
… More
cantly decreased and the frequency of micturition and basal pressure were significantly increased. These changes in urodynamic parameters may characterize the detrusor overactivity occurring in CYP-treated rats. Thus, CYP treatment has been shown to cause down-regulation of pharmacologically relevant receptors in the bladder of rats. The present study offers further pharmacological evidence that both muscarinic and purinergic mechanisms contribute significantly to the urinary dysfunction due to IC.
3) The angiotensin II (Ang II) receptor was significantly up-regulated in the rat bladder due to the bladder outlet obstruction. Repeated oral administration of telmisartan in rats completely prevented the development of a bladder outlet obstruction-induced up-regulation of bladder Ang II receptors. Telmisartan treatment also effectively attenuated the increase in bladder wet weight caused by urinary outlet obstruction. Thus, bladder Ang II may be at least partly associated with the pathogenesis of urinary dysfunction occurring subsequent to bladder outlet obstruction.
The present study raise the possibility that agonists or antagonists of pharmacologically relevant receptors in the bladder is a useful therapeutic drug for the treatment of urinary dysfunction. Less
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