| Co-Investigator(Kenkyū-buntansha) |
ARAKI Isao 滋賀医科大学, 医学部, 准教授 (50252424)
ZAKOUJI Hidenori 山梨大学, 大学院・医学工学総合研究部, 助教 (60345717)
KOBAYASHI Hideki 山梨大学, 大学院・医学工学総合研究部, 助教 (50402053)
YOSHIYAMA Mitsuharu 山梨大学, 大学院・医学工学総合研究部, 医学研究員 (20422694)
TOMINAGA Makoto 大学共同利用機関法人自然科学研究機構(共通施設), 教授 (90260041)
FUKASAWA Mizuya 山梨大学, 医学部附属病院, 講師 (80252039)
MOCHIZUKI Tsutomu 山梨大学, 大学院・医学工学総合研究部, 医学研究員 (50377496)
SAWADA Norifumi 山梨大学, 医学部附属病院, 助教 (70402055)
TSUCHIDA Takayuki 山梨大学, 医学部附属病院, 講師 (30217327)
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| Budget Amount *help |
¥19,760,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥4,560,000)
Fiscal Year 2010: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2009: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2008: ¥10,530,000 (Direct Cost: ¥8,100,000、Indirect Cost: ¥2,430,000)
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| Research Abstract |
In the urine storage phase, mechanical stretch stimulates bladder afferents. These urinary bladder afferent sensory nerves consist of small diameter Aδ- and C-fibers running in the hypogastic and pelvic nerves. Neuroanatomical studies have revealed a complex neuronal network within the bladder wall. The exact mechanisms that underline mechano-sensory transduction in bladder afferent terminals remain ambiguous ; however, a wide range of ion channels (e.g. TTX-resistant Na+ channels, Kv channels and hyperpolarization-activated cyclic nucleotidegated cation channels, degenerin/epithelial Na+ channel), and receptors (e.g. TRPV1, TRPM8, TRPA1, P2X2/3, etc.) have been identified at bladder afferent terminals and have implicated in the generation and modulation of afferent signals, which are elcited by a wide range of bladder stimulations including physiological bladder filling, noxious distension, cold, chemical irritation and inflammation. The mammalian transient receptor potential (TRP) family consists of 28 channels that can be subdivided into six different classes : TRPV (vanilloid), TRPC (canonical), TRPM (Melastatin), TRPP (Polycystin), TRPML (Mucolipin), and TRPA (Ankyrin). TRP channels are activated by a diversity of physical (voltage, heat, cold, mechanical stress) or chemical (pH, osmolality) stimuli and by binding of specific ligands, enabling them to act as multifunctional sensors at the cellular level. TRPV1, TRPV2, TRPV4, TRPM8, and TRPA1 have been described in different parts of the urogenital tract. Although only TRPV1 among TRPs has been extensively studied so far, more evidence is slowly accumulating about the role of other TRP channels, ion channels, and receptors in the pathophysiology of the urogenital tract, and may provide a new strategy for the treatment of bladder dysfunction.
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