2007 Fiscal Year Final Research Report Summary
Analysis of urinary dysfunction and drug discovery by in vivo measurement of drug-receptor binding
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 |
Section | 一般 |
Research Field |
General pharmacology
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Research Institution | University of Shizuoka |
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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Keywords | Benign urostatic hvnernlasia / Overactive bladder / Urinary bladder / Neurotransmitter receptors / Cerebral infarction / Bladder outlet obstruction / Interstitial |
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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Research Products
(47 results)
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[Journal Article] Comparative evaluation of central muscarinic receptor binding activity by oxybutynin, tolterodine and darifenacin used to treat overactive bladder2007
Author(s)
Tomomi, Oki, Aiko, Kageyama, Yukiko, Takagi, Shinya, Uchida, Shizuo, Yamada
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Journal Title
J. Urol 177
Pages: 766-770
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Muscarinic and alpha 1-adrenergic receptor binding characteristics of saw palmetto extract in rat lower urinary tract.2007
Author(s)
Mayumi, Suzuki, Tomomi, Oki, Tomomi, Sugiyama, Keizo, Umegaki, Shinya, Uchida, Shizuo, Yamada
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Journal Title
Urology 69
Pages: 1216-1220
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Brain neurotransmitter receptor-binding characteristics in rats after oral administration of haloperidol, risperidone and olanzapine2007
Author(s)
Shinya, Uchida, Yasuhiro, Kato, Kazufumi, Hirano, Yoshiyuki, Kagawa, Shizuo, Yamada
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Journal Title
Life Sci 80
Pages: 1635-1640
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Comparative measurement of spinal CSF microdialysate concentrations and concomitant antinociception of morphine and morphine-6β-glucuronide in rats.2007
Author(s)
Takashi, Okura, Noriyuki, Komiyama, Yuki, Morita, Midori, Kimura, Yoshiharu, Deguchi, Shizuo, Yamada
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Journal Title
Life Sci 80
Pages: 1319-1326
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Urodynamics and bladder muscarinic receptors in rats with cerebral infarction and bladder outlet obstruction2007
Author(s)
Shuji, Maruyama, Souhei, Kurosawa, Yukiko, Takagi, Tomomi, Oki, Yukiko, Noguchi, Masashi, Ukai, Hironori, Yuyama, Akiyoshi, Ohtake, Masanori, Suzuki Masao, Sasayama, Shizuo, Yamada
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Journal Title
Neurosci. Lett 414
Pages: 80-84
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] from plasma concentrations of silodosin, tamsulosin and terazosin to treat urinary obstruction in benign prostatic hyperplasia.Biol.2007
Author(s)
Shizuo, Yamada, Yasuhiro, Kato, Takashi, Okura, Yoshiyuki, Kagawa, Kazuki, Kawabe Prediction of a_1-adrenoceptor occupancy in the human prostate
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Journal Title
Pham. Bull 30
Pages: 1237-1241
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Binding activities by propiverine and its N-oxide metabolites of voltage-dependent L-type calcium channel antagonist receptors in the rat bladder and brain2007
Author(s)
Shinya, Uchida, Souhei, Kurosawa, Tomomi, Fujino (Oki), Yoshihisa, Kato Masato, Nanri, Kenichiro, Yoshida, Shizuo, Yamada
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Journal Title
Life Sci 80
Pages: 2454-2460
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A Novel mechanism for polychlorinated biphenyl-induced decrease in serum throxine level in rats.2007
Author(s)
Yoshihisa, Kato, Shin-ichi, Ikushiro, Rie, Takiguchi, Koichi, Haraguchi, Nobuyuki, Koga, Shinya, Uchida, Toshiyuki, Sakaki, Shizuo, Yamada, Jun, Kanno, Masakuni, Degawa
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Journal Title
Drug Metab. Dispos 35
Pages: 1949-1955
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Human muscarinic receptor binding characteristics of antimuscarinic agents to treat overactive bladder.2006
Author(s)
Shuji, Maruyama, Tomomi, Oki, Atsushi, Otsuka, Hitoshi, Sninbo, Seichiro, Ozono, Shinji, Kageyama, Isao, Araki, Yuuki, Mikami, Masayuki, Takeda, Shizuo, Yamada
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Journal Title
J. Urol 175
Pages: 365-369
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Selective protection of curcumin against carbon tetrachloride-induced inactivation of hepatic cytochrome P450 isozymes in rats2006
Author(s)
Tomomi, Sugiyama, Jun-ichi, Nagata, Azumi, Yamagishi, Kaori, Endoh, Morio, Saito Kazuhiko, Yamada, Shizuo, Yamada, Keizo, Umegaki
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Journal Title
Life Sci 78
Pages: 2188-2193
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Development of dry powder inhalation system of novel vasoactive intestinal peptide (VIP) analogue for pulmonary administration2006
Author(s)
Yuki, Ohmori, Satomi, Onoue, Kosuke, Endo, Asami, Matsumoto, Shinya, Uchida, Shizuo, Yamada
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Journal Title
Life Sci 79
Pages: 138-143
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Stereochemical diversity-oriented conformational restriction strategy. Development of potent histamine H_3 and/or H_4 receptor antagonists with a imidazolylcyclopropane structure.2006
Author(s)
Mizuki, Watanabe, Yuji, Kazuta, Hideki, Hayashi, Shizuo, Yamada, Akira, Matsuda, Satoshi, Shuto
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Journal Title
J. Med. Chem 49
Pages: 5587-5596
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Effects of Ginkgo biloba extract on pharmacokinetics and pharmacodynamics of tolbutamide and midazolam in healthy volunteers.2006
Author(s)
Shinya, Uchida, Hiroshi, Yamada, Xiao, Dong, Li, Syuji, Maruyama, Yuki, Ohmori, Tomomi, Oki, Hiroshi, Watanabe, Keizo, Umegaki, Kyoichi, Ohashi, Shizuo, Yamada
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Journal Title
J. Clin. Pharmacol 46
Pages: 1290-1298
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Structure-activity relationship of receptor binding of some 1,4-dihydropyridine derivatives2007
Author(s)
Shizuo, Yamada, Daiki, Takahashi, Luvsandorj, Oyunzul, Satomi, Onoue, Yoshihiko, Ito. Shinva, Uchida, Rahime, Simsek, Miyase, Gozde Gunduz, Cihat, Safak
Organizer
5th Mt. Symp. on Pharm. Chem
Place of Presentation
Istanbul
Year and Date
2007-09-05
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Antinociceptive effect of extracts of medical herbs in mice and their interaction with morphine2007
Author(s)
Shinya, Uchida, Keita, Hirai, Junko, Hanato, Yukiko, Shinme, Shizuo, Yamada
Organizer
The 3rd China-Japan Joint Meeting ofBasic and Clinical Pharmacology
Place of Presentation
Dailen, Chaina
Year and Date
2007-08-24
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Direct quantification of muscarinic receptor subtypes in human detrusor muscle, mucosa and parotid gland by irreversible inactivation of M3 receptors by 4-DAMP musterd2007
Author(s)
Kazuhiro, Suzuki, Shuji, Maruyama, Masayuki, Takeda, Atsushi, Otsuka, Siichiro, Ozono, Shizuo, Yamada
Organizer
37th Annual Meeting of the Mt. Continence Soc.
Place of Presentation
Rotterdam, Netherlands
Year and Date
2007-08-23
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Muscarinic and purinergic receptors are altered in the bladder of rat models with interstitial cystitis2006
Author(s)
Aiko, Kageyama, Tomomi, Oki, Luvsandorj, Oyunzul, Shohei, Kurosawa, Shizuo, Yamada
Organizer
Int. Continence Ann. Meeting
Place of Presentation
Christchurch , New Zealand
Year and Date
20061128-1201
Description
「研究成果報告書概要(欧文)」より
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[Presentation] The active metabolite (DPr-P-4(N→O)) of propiverine hydrochloride may contribute to the bladder selectivity of this drug to treat patients with overactive bladder2006
Author(s)
Shizuo, Yamada, Tomomi, Oki, Shuji, Maruyama, Kenichiro, Yoshida, Masato, Nanri, Masayuki, Takeda
Organizer
Int. Continence Ann. Meeting
Place of Presentation
Christchurch , New Zealand
Year and Date
20061128-1201
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Comparative evaluation of human mucosa and detrusor muscarinic receptor binding by anticholinergic agents in the treatment of overactive bladder2006
Author(s)
Tomomi, Oki, Luvsandorj, Oyunzul, Kazuhiro, Suzuki, Aiko, Kageyama, Atsushi, Otsuka, Hitoshi, Shinbo, Seiichiro, Ozono, Shizuo, Yamada
Organizer
Int. Continence Ann. Meeting
Place of Presentation
Christchurch , New Zealand
Year and Date
2006-12-01
Description
「研究成果報告書概要(欧文)」より
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[Presentation] A possible mechanism for the decrease in serum thyroxine level by polychlorinated biphenyls in Wistar and Gunn rats2006
Author(s)
Yoshihisa, Kato, Shin-ichi, Ikushiro, Rie, Takiguchi, Sekihiro, Tamaki, Koichi, Haraguchi, Toshiyuki, Sakaki, Shizuo, Yamada, Jun, Kanno, Masakuni, Degawa
Organizer
26th International Symposium on Halogenated Persistent Organic Pollutants
Place of Presentation
Oslo, Norway
Year and Date
2006-08-21
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Effects of ursodeoxycholic acid on the CYP3A activity and pharmacokinetics of midazolam in rats2006
Author(s)
Shinva, Uchida, Shohei, Kurosawa, Shingen, Misaka, XiaoDong, Li, DongMei, Yan, Hiroshi, Watanabe, Kyoichi, Ohashi, Shizuo, Yamada
Organizer
The 15th World Congress of Pharmacology
Place of Presentation
Beijing, China
Year and Date
2006-07-04
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Effects of Ursodeoxycholic acid on the CYP3A activity and pharmacokinetics of midazolam in rats and healthy volunteers2006
Author(s)
Shinya, Uchida, Shohei, Kurosawa, Shingen, Misaka, Hiroshi, Watanabe, Kyoichi, Ohashi Shizuo, Yamada
Organizer
The 1st Asia Pacific ISSX Meeting
Place of Presentation
Jeju, Korea
Year and Date
2006-05-24
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Pharmacokinetic, Receptor binding and Pharmacodynamic Anlaysis of CNS Drugs2006
Author(s)
Shizuo, Yamada, Kazufumi, Hirano, Tomomi, Oki, Akihiko, Urayama, Shinya, Uchida
Organizer
CINP Asia Pacific Regional Meeting
Place of Presentation
Pattaya, Thailand
Year and Date
2006-03-14
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Hiroshi Watanabe Influences of CYP2C9 genotype on pharmacokinetics and pharmacodynamics of benzbromarone2006
Author(s)
Shinya, Uchida, Kayoko., Shimada, Shingen, Misaka, Don Mei, Yan, Xiao Dong, Li, Shinichiro, Nishio, Hiromitu, Imai, Kyoichi, Ohashi, Shizuo, Yamada
Organizer
2005 Annual Meeting ofAmerican Society for Clinical Pharmacologyand Therapeutic
Place of Presentation
Baltimore, USA
Year and Date
2006-03-08
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Propiverine and oxybutynin inhibit Ca^<2+> influx mediated by the activation of a specific receptor, transient recepter potential vanilloid subtype 1 (TRPV1)
Author(s)
Aiko, Kageyama, Yusaku, Iwasaki, Tatsuo, Watanabe, Masato, Nanri, Kenichiro, Yoshida, Shizuo, Yamada
Organizer
37th Annual Meeting of the Int. Continence Soc.
Place of Presentation
Rotterdam, Netherlands
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Demonstration of muscarinic and nicotinic receptor binding acticities of acetylcholinesterase inhibitors to treat impaired detrusor contractility
Author(s)
Kazumi, Fushimi, Yuki, Ishida, Taketsugu, Harada, Yoshihiko, Ito, Saori, Nishijima, Kimio, Sugaya, Shizuo, Yamada
Organizer
37th Annual Meeting of the Int. Continence Soc.
Place of Presentation
Rotterdam, Netherlands
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Propiverine and its N-oxide metabolite bind significantly to L-type calcium channel antagonist receptors in rat bladder
Author(s)
Shizuo, Yamada, Yoshihiko, Ito, Tomomi, Fujino, Masato, Nanri, Kenichiro, Yoshida
Organizer
37th Annual Meeting of the Mt. Continence Soc.
Place of Presentation
Rotterdam, Netherlands
Description
「研究成果報告書概要(欧文)」より