Basic Research for Development of New Pharmacotherapy for Neurogenic Voiding Dysfunction

神经源性排尿障碍新药物开发的基础研究

基本信息

  • 批准号:
    09671598
  • 负责人:
  • 金额:
    $ 2.05万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    1997
  • 资助国家:
    日本
  • 起止时间:
    1997 至 1999
  • 项目状态:
    已结题

项目摘要

Histological studies using in situ hybridization combined with retrograde Fast Blue labeling revealed that expressions of subunit mRNAs of both AMPA and NMDA receptor channels are distinct between parasympathetic preganglionic neurons (PGNs) and somatomotor neurons in the ventral horn (Onuf nucleus), indicating different functional properties in regard to AMPA and NMDA glutamate receptors between PGNs and Onuf nucleus.Electrophysiological studies in the rat revealed that AMPA and NMDA glutamatergic synaptic mechanisms play a key role in the spinal processing of afferent input from the bladder and that these mechanisms function synergistically in the ascending limb of the spinobulbospinal micturition reflex pathway. Another set of physiological studies showed that a selective 5-HTィイD21AィエD2 receptor antagonist inhibited the descending limb but not the ascending limb of the spinobulbospinal micturition reflex pathway via actions on the lumbosacral spinal cord, suggesting a role of 5-HTィイD21AィエD2 receptor in the central neural mechanisms controlling micturition. Regarding the effects of metabotropic glutamate receptor (mGluR) agonist or antagonist, MCPG , an antagonist of mGluR I and II , did not block micturition reflex, while trans-ACPD, an agonist of mGluR II, III, V and I, inhibited micturition reflex if injected intrathecally at lumbosacral spinal cord level but not injected intravenously. The effect of trans-ACPD was mediated at least, by the action on the descending limb of the micturition reflex pathway.From these data, pharmacotherapy targeting on glutamate receptors and 5-HT (serotonin) receptors within the spinal cord will be a promising modality to manage voiding dysfunction in patients with neurological diseases.
组织学研究表明,AMPA和NMDA受体通道的亚单位mRNA在腹角副交感节前神经元(PGN)和躯体运动神经元中的表达不同(Onuf核),表明PGNS和Onuf核之间AMPA和NMDA谷氨酸受体的不同功能特性。大鼠的电生理研究表明,AMPA和NMDA神经元能突触机制在脊髓处理来自膀胱的传入输入中起关键作用,并且这些机制在脊髓延髓脊髓排尿反射通路的上升支中协同起作用。另一组生理学研究表明,选择性5-HT受体D21 A受体D2拮抗剂通过作用于腰骶脊髓抑制脊髓延髓排尿反射通路的下行支,但不抑制上行支,提示5-HT受体D21 A受体D2在控制排尿的中枢神经机制中起作用。在代谢型谷氨酸受体(mGluR)激动剂或拮抗剂的作用方面,mGluR I和II的拮抗剂MCPG不阻断排尿反射,而mGluR II、III、V和I的激动剂trans-ACPD在腰骶脊髓水平鞘内注射时抑制排尿反射,而静脉注射则不阻断。trans-ACPD的作用至少是通过对排尿反射通路下行支的作用介导的,从这些数据来看,针对脊髓内谷氨酸受体和5-HT(5-羟色胺)受体的药物治疗将是一种有前途的治疗神经系统疾病患者排尿功能障碍的方式。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
T.SHIBATA: "Different expression of AMPA and NMDA receptor subunit mRNAs between visceromotor and sematomotor neurons of the rat lumbosacral spinal cord"The Journal of Comparative Neurology.
T.SHIBATA:“大鼠腰骶脊髓内脏运动神经元和作动神经元之间 AMPA 和 NMDA 受体亚基 mRNA 的差异表达”比较神经学杂志。
  • DOI:
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  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Kakizaki H, et al.: "Rele of Spinal Glutamat;ergic Transmission in the Ascending Limb of the Micturition Reflex Pathway in the Rat"The Journal of Pharmacology and Experirnental Therapeutics. 285. 22-27 (1998)
Kakizaki H 等人:“脊髓谷氨酸的关系;大鼠排尿反射通路上升肢的能传递”,药理学和实验治疗学杂志。
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    0
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KAKIZAKI Hidehiro其他文献

KAKIZAKI Hidehiro的其他文献

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{{ truncateString('KAKIZAKI Hidehiro', 18)}}的其他基金

Comprehensive analysis of abnormal bladder sensation andurothelial dysfunction in overactive bladder
膀胱过度活动症膀胱感觉异常及尿路上皮功能障碍的综合分析
  • 批准号:
    19591831
  • 财政年份:
    2007
  • 资助金额:
    $ 2.05万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Research on The Development of Overactive Bladder after Bladder Outlet Obstruction : Basic Research in Rat Model with Partial Urethral Obstruction
膀胱出口梗阻后膀胱过度活动症发展的研究:部分尿道梗阻大鼠模型的基础研究
  • 批准号:
    14370500
  • 财政年份:
    2002
  • 资助金额:
    $ 2.05万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Research for Establishing Bladder Reconstruction with Tissue Engineering
利用组织工程建立膀胱重建的研究
  • 批准号:
    13671629
  • 财政年份:
    2001
  • 资助金额:
    $ 2.05万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)

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