INVESTIGATIONS INTO THE MOLECULAR TARGETED THERAPY FOR OVERACTIVE BLADDER BY REGULATING INTERCELLULAR SIGNAL TRANSMISSION SYSTEM
| Project/Area Number |
17390443
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | NAGOYA CITY UNIVERSITY |
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Principal Investigator |
HASHITANI Hikaru Nagoya City Univ., Grad.Sch.Med.Sci., Assistant Professor, 大学院医学研究科, 講師 (10315905)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Hikaru Nagoya City Univ., Grad.Sch.Med.Sci., Professor, 大学院医学研究科, 教授 (80037548)
KUBOTA Yasue Nagoya City Univ., Grad.Sch.Med.Sci., Research Associate, 大学院医学研究科, 助教 (00381830)
KOHRI Kanjiro Nagoya City Univ., Grad.Sch.Med.Sci., Professor, 大学院医学研究科, 教授 (30122047)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥15,800,000 (Direct Cost: ¥15,800,000)
Fiscal Year 2006: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2005: ¥11,300,000 (Direct Cost: ¥11,300,000)
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| Keywords | INTERSTITIAL CELL / SMOOTH MUSCLE / OVERACTIVE BLADDER / INTRACLLULARCALCIUM / PACEMAKER CELL / INTRACELLULAR CALCIUM STORE / KIT RECEPTOR / BLADDER OUTLET OBSTRUCTION / 細胞内カルシウム濃度 / ギャップ結合 / Kit免疫反応陽性細胞 |
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| Research Abstract |
1. Two weeks after partial bladder outlet obstruction, population of Kit/vimentin immunoreactive interstitial cells (ICs) was increased in bladders of the guinea-pig which exhibited bladder overactivity during filling cystometry. Electron microscopy characterized ultrastructural morphology of ICs by their numerous mitochondria and close contact with each other and with neighbouring detrusor smooth muscle cells or nerves. These results suggest that the altered distribution of ICs may contribute to the pathophysiology of bladder overactivity.
2. Spontaneous Ca transients in ICs of the rabbit urethra in situ rely on both Ca release from intracellular Ca stores and Ca influx through non L-type Ca channel pathways. ICs often exhibited Ca transients synchronously with each other, but did not often show a close temporal relationship with Ca transients in urethral smooth muscle cells (USMCs), suggesting that they may not act as a coordinated pacemaker electrical network rather randomly increase
… More
excitability of USMCs.
3. NO caused an enhancement of spontaneous contractions in detrusor smooth muscle (DSM) of the guinea-pig bladder by spontaneous accelerating action potentials through cGMP-independent mechanisms, whilst cGMP itself has inhibitory effects on DSM contractility. Sildenafil may indirectly suppress DSM contractility by diminishing synchronicity between DSM bundles without inhibiting excitability of DSM themselves.
4. ICs in corpus cavernosum (CC) of the rabbit release prostaglandins via cyclooxygenase-2 (COX-2) activity and reinforce not only spontaneous but also nerve-mediated a-adrenergic contractions. Neurally-released NO initiates CC smooth muscle relaxations mainly by a Ca-independent mechanism but may be associated with a reduction in Ca to maintain penile erection.
5. In the guinea-pig bladder, T-type Ca channels in DSM may account for the preceding depolarizations which lead to action potentials, whilst Ca influx through these channels may couple functionally to small conductance Ca-activated K channels to stabilize the resting membrane potential. Less
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Report
(3 results)
Research Products
(21 results)
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[Journal Article] Intercellular communications within the rat anterior pituitary XII : immunohistochemicaland physiological evidences for the gap junctional coupling of the folliculo-stellate cells in the rat anterior pituitary.2005
Author(s)
Sato Y, Hashitani H, Shirasawa N, Sakuma E, N aito A, Suzuki H, Asai Y, Sato G, Wada I, Herbert DC, Soji T.
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Journal Title
Tissue & Cell 37
Pages: 281-291
Related Report
