| Project/Area Number |
08671812
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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 | KYOTO UNIVERSITY |
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Principal Investigator |
KAKEHI Yoshiyuki Kyoto University Graduate School of Medicine, Assistant Professor, 医学研究科, 講師 (20214273)
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| Co-Investigator(Kenkyū-buntansha) |
OKUNO Hiroshi Kyoto university Graduate School of Med.Instructor, 医学研究科, 助手 (90263079)
OKADA Yusaku Kyoto University Graduate School of Med.Associate Professor, 医学研究科, 助教授 (20127062)
YOSHIDA Osamu Kyoto University Graduate School of Med.Professor, 医学研究科, 教授 (70025584)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | micturition reflex / ion-channel / plasticity / neurotransmitter / nitric oxide / bladder efferent pathway / whole-cell patch clamp / nerve growth factor / イオンチャネル / ホールセルパッチクランプ / 膀胱運動路 |
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| Research Abstract |
(1) Primary afferent neurons in dorsal root ganglia (DRG) and efferent neurons in major pelvic ganglia innervating the urinary bladder were labeled by retrograde axonal transport of a fluorescent dye (Fast Blue) injected into the bladder wall in female adult rats. Bladder afferent and efferent neurons were then dissociated using enzymatic solution including trypsin and identified by a fluorescent microscope.
(2) Electrophysiological studies using whole-cell patch clamp recording techniques were performed to examine the effects of nitric oxide (NO), which is one of neurotransmitters regulating lower urinary tract function on dissociated bladder afferent and efferent neurons. An application of SNAP,an NO donor, inhibited calcium channel currents by 30% in bladder afferent neurons. These inhibitory effects were mimicked by an application of 8-bromo-cyclic-GMP,membrane permeable cyclic-GMP,and the NO-mediated inhibition of calcium channel currents was then antagonized by an preincubation of ODQ,a NO-dependent guanylate cyclase inhibitor. These results indicate that NO has an inhibitory effect on bladder afferent pathway via cyclic-GMP dependent mechanisms (these data have been presented at 27th Annual meeting of Society for Neuroscience, USA)
Effects of nerve growth factor (NGF) on bladder afferent and efferent neurons were investigated using whole-cell patch clamp recording techniques. In contrast to NO,an application of NGF increased calcium channel currents by 30% in bladder afferent neurons. These facilitatory effects of NGF on calcium channel currents were mainly observed in C-fiber bladder afferent neurons which exhibited tetrodotoxin (TTX)-resistant sodium currents. These results indicate that NGF can modulate excitability of bladder afferent neurons, and therefore might contribute to an emergence of bladder hyperreflexia.
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