Reseaarch on the function and development of new therapy for Ion channels in the lower urinary tract

下尿路离子通道的功能研究及新疗法的开发

• 批准号: 20390423
• 负责人: TAKEDA Masayuki
• 金额: $ 12.65万
• 依托单位: University of Yamanashi
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20390423/
• 关键词: イオンチャネル; 膀胱上皮細胞; 細胞内カルシウムイオン; TRP TRPV4; TRP; TRPV4; メカノセンサー; 過活動膀胱; ATP; 求心性伝達機構; 尿路上皮

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.

在储尿期，机械拉伸刺激膀胱传入。这些膀胱感觉神经由小直径的A、δ和C纤维组成，分布于下腹神经和盆神经。神经解剖学研究揭示了膀胱壁内复杂的神经元网络。膀胱传入末梢机械感觉转导的确切机制尚不清楚；然而，广泛的离子通道(如TTX抗性Na+通道、Kv通道和超极化激活的环核苷酸脱氢阳离子通道、退行性/上皮性Na+通道)和受体(如TRPV1、TRPM8、TRPA1、P2X2/3等)。在膀胱传入终末被发现，并与传入信号的产生和调制有关，这些传入信号被广泛的膀胱刺激所释放，包括生理膀胱充盈、伤害性扩张、寒冷、化学刺激和炎症。哺乳动物瞬时受体电位(TRP)家族由28个通道组成，可分为六类：TRPV(香草样)、TRPC(典范)、TRPM(Melastatin)、TRPP(多囊蛋白)、TRPML(粘膜脂)和TRPA(Ankyrin)。Trp通道被各种物理刺激(电压、热、冷、机械应力)或化学刺激(pH、渗透压)激活，并通过特定配体的结合而激活，使它们能够在细胞水平上充当多功能传感器。TRPV1、TRPV2、TRPV4、TRPM8和TRPA1已在泌尿生殖道的不同部位被描述。尽管到目前为止，在TRPs中只有TRPV1得到了广泛的研究，但关于其他Trp通道、离子通道和受体在泌尿生殖道病理生理中的作用的证据正在慢慢积累，并可能为膀胱功能障碍的治疗提供一种新的策略。

项目成果

Suppression of NF-KB by cyclosporine A and tacrolimus (FK506) via induction of the C/EBP family : Implication for unfolded protein response.

环孢素 A 和他克莫司 (FK506) 通过诱导 C/EBP 家族抑制 NF-KB：对未折叠蛋白反应的影响。

• 发表时间: 2009
• 期刊: J Immunol. 182
• 作者: Yoshitomi T;Enokida H;Seki N;Nakagawa M.;S.DU
• 通讯作者: S.DU

Pure laparoscopic partial nephrectomy for primary renal carcinoid,

单纯腹腔镜肾部分切除术治疗原发性肾类癌，

• 发表时间: 2009
• 期刊: Japanese Society of Endourology and ESWL 22
• 作者: Imamoto T;et al.;Norifumi SAWADA
• 通讯作者: Norifumi SAWADA

Committee 2-Cell Biology, Vol.1, "Incontinence 4^<TH> ed.", Abrams, P., Cardozo, L., Khoury, S., Wein, A.ed.

委员会 2 细胞生物学，第 1 卷，“失禁 4^<TH> ed.”，Abrams, P.、Cardozo, L.、Khoury, S.、Wein, A.ed.

• 发表时间: 2009
• 作者: Fry;C.H
• 通讯作者: C.H

Incontinence and detrusor dysfunction associated with pelvic organ prolapse: clinical value of preoperative urodynamic evaluation

• DOI: 10.1007/s00192-009-0954-2
• 发表时间: 2009-11-01
• 期刊: INTERNATIONAL UROGYNECOLOGY JOURNAL
• 影响因子: 1.8
• 作者: Araki, Isao;Haneda, Yaburu;Takeda, Masayuki
• 通讯作者: Takeda, Masayuki

Solifenacin as add-on therapy for overactive bladder symptoms ? ASSIST, randomized controlled study - Urology

索利那新作为膀胱过度活动症症状的附加疗法？

• 发表时间: 2011
• 期刊: randomized controlled study - Urology
• 作者: Osamu Yamaguchi;Hidehiko Kakizaki;Yukio Homma;Masayuki Takeda;Osamu Nishizawa;Momokazu Gotoh;Osamu Yokoyama;Narihito Seki;Masaki Yoshida on behalf of the ASSIT Study Group
• 通讯作者: Masaki Yoshida on behalf of the ASSIT Study Group