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A study of the histamine neuron system : Its correlation to newly-discovered hypothalamic peptides.

A study of the histamine neuron system : Its correlation to newly-discovered hypothalamic peptides.
组胺神经元系统的研究:其与新发现的下丘脑肽的相关性。
批准号:
14370027
负责人:
YANAI Kazuhiko
金额:
$8.9万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (B)
财政年份:
2002
资助国家:
日本
项目状态:
已结题
起止时间:
2002 至 2004

项目摘要

项目成果

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中文摘要
翻译
食欲素是专门定位于下丘脑外侧区神经元的神经肽,它向大多数单胺能核,如去甲肾上腺素能蓝斑、多巴胺能腹侧被盖区和组胺能结节乳头核发出投射。本研究旨在研究食欲素在小鼠伤害性感受中的作用。C57BL/6小鼠脑室注射食欲素A和食欲素B,鞘内注射食欲素A和食欲素B。和皮下(S.C.)揭示这些多肽的作用部位,并用四种伤害性任务检测痛阈值。在所有四种类型的热(热板、甩尾、缩爪)、机械(尾压)、化学(福尔马林、辣椒素和腹部伸展)痛觉和伤害素诱导的行为反应中,食欲素均表现出抗伤害性反应。或IT,而S.C.管理不力。食欲素A的抗伤害性作用更多的是…比食欲素B更有说服力。服用食欲素A的效果与I.T.相当,甚至更有效。行政管理。食欲素A的作用可被腺苷1型受体拮抗剂1,3-二丙基-8-环戊基黄嘌呤(DPCPX)和茶碱完全阻断,但不能被纳洛酮阻断,提示腺苷神经元和/或腺苷途径可能参与了食欲素的作用。重症监护室。给予伤害素对大脑和脊髓中增食欲素的表达没有显著影响。目前的发现表明,食欲素在至少四种不同类型的疼痛中具有抗伤害性作用,可能同时作用于大脑和脊髓。越来越多的证据表明,组胺能神经元系统与精神分裂症的病理生理学有关。本研究的目的是用正电子发射断层扫描(PET)技术比较精神分裂症患者和正常人体内组胺H_1受体的分布。用正电子发射计算机断层扫描(PET)和H_1受体的放射性配基多塞平测定了10例正常人和10例精神分裂症患者的H_1受体结合。[^<11>C]多塞平与脑内可用H_1受体的结合势(BP=Bmax/K_D)是通过逐个体素的图形分析计算的,并用感兴趣区(ROI)和统计参数图(SPM99)比较了精神分裂症患者和正常人之间的差异。精神分裂症患者额叶、前额叶皮质和扣带回H_1受体的BP值明显低于对照组。相反,精神分裂症患者的大脑中没有H_1受体显著高于对照组的区域。我们的研究结果表明,中枢组胺能神经元系统可能参与了精神分裂症的病理生理学,尽管还需要进一步的研究来证实这一假说。较少
英文摘要
Orexins are neuropeptides located exclusively in neurons of the lateral hypothalamic area, which send projections to most monoaminergic nuclei, such as noradrenergic locus coeruleus, dopaminergic ventral tegmental areas, and histaminergic tuberomammillary nuclei. The present work was carried out to examine the role of orexins in nociception in mice. C57BL/6 mice were administered with orexin A and B intracerebroventricularly(i.c.v.), intrathecally(i.t.) and subcutaneously(s.c.) to reveal the sites of action of these peptides and to examine the pain thresholds using four kinds of nociceptive tasks. Orexins showed antinociceptive effects in all four types of assays for thermal (hot-plate, tail-flick, paw-withdrawal), mechanical (tail-pressure), chemical (formalin, capsaicin and abdominal stretch) nociceptions and nociceptininduced behavioral responses, when administered i.c.v. or i.t., whereas the s.c. administration was ineffective. The antinociceptive effects of orexin A were more rema … More rkable than those of orexin B. The i.c.v. administration of orexin A was as effective as, or more potent than the i.t. administration. The effects of orexinAwere completely blocked by adenosine type 1 receptor antagonists, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) and theophylline, but not by naloxone, suggesting a possible involvement of the adenosine-containing neurons and/or the adenosine pathway in these orexin actions. The i.c.v. administration of nociceptin had no significant effects on orexin expression in the brain and spinal cord. The present findings suggest that orexins have an antinociceptive role in at least four different types of pains, probably acting on both the brain and spinal cord.Increasing evidence has shown that the histaminergic neuron system is implicated in the pathophysiology of schizophrenia. The aim of this study was to compare the distribution of histamine H_1 receptors between schizophrenics and normal human subjects in vivo using positron emission tomography (PET). H_1 receptor binding was measured in 10 normal subjects and 10 medicated schizophrenic patients by PET and [^<11>C] doxepin, a radioligand for the H_1 receptor. The binding potential (BP=Bmax/K_D) of [^<11>C] doxepin for available brain H_1 receptors was calculated by a graphical analysis on voxel-by-voxel basis and compared between schizophrenics and normal subjects using the regions of interest (ROIs) and the statistical parametrical mapping (SPM99). BP values for H_1 receptors in the frontal and prefrontal cortices and the cingulate gyrus were significantly lower among the schizophrenic patients than among the control subjects. On the contrary, there were no areas of the brain where H_1 receptors were significantly higher among the schizophrenic patients than the control subjects. The results of our study suggest that the central histaminergic neuron system could be involved in the pathophysiology of schizophrenia, although further studies are needed to confirm this hypothesis. Less
期刊论文(62)
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会议论文
J.I.Mobarakeh et al.: "Enhanced antinociception by intrathecally-administered morphine in histamine H_1 receptor gene knockout mice"Neuropharmacology. 42(8). 1079-1088 (2002)
J.I.Mobarakeh 等人:“组胺 H_1 受体基因敲除小鼠鞘内注射吗啡增强抗伤害作用”神经药理学。
DOI: --
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作者: []
通讯作者:
K.Yanai, T.Watanabe: "Histamine as a neurotransmitter in the CNS"Sping MED(in press). (2004)
K.Yanai、T.Watanabe:“组胺作为中枢神经系统中的神经递质”Sping MED(出版中)。
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Effects of serotonin-dopamine antagonist on prepulse inhibition and Neurotransmitter contents in the rat brain.
血清素-多巴胺拮抗剂对大鼠脑前脉冲抑制和神经递质含量的影响。
DOI: --
发表时间: 2004
期刊: Nerosci.Lett. 366
影响因子: --
作者: [T.Ojima et al.]
通讯作者: T.Ojima et al.
H.Mochizuki et al.: "Imaging of central itch modulation in the human brain using positron emission tomography"Pain. 105(1-2). 339-346 (2003)
H.Mochizuki 等人:“使用正电子发射断层扫描对人脑中枢瘙痒调节进行成像”疼痛。
DOI: --
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共 24 条
    Molecular mechanism of brain histamine clearance
    • 批准号:
      26670117
    • 项目类别:
      Grant-in-Aid for Challenging Exploratory Research
    • 资助金额:
      $2.41万
    • 财政年份:
      2014
    • 负责人:
      YANAI Kazuhiko
    • 依托单位:
    Integrated research of histamine system from molecular to wholeanimals and humans using leading-edge technologies
    • 批准号:
      21390171
    • 项目类别:
      Grant-in-Aid for Scientific Research (B)
    • 资助金额:
      $12.48万
    • 财政年份:
      2009
    • 负责人:
      YANAI Kazuhiko
    • 依托单位:
    Molecular Neuropharmacology on histamine system : From basic to clinical investigation on unsolved issues
    • 批准号:
      19390061
    • 项目类别:
      Grant-in-Aid for Scientific Research (B)
    • 资助金额:
      $12.06万
    • 财政年份:
      2007
    • 负责人:
      YANAI Kazuhiko
    • 依托单位:
    The new perspectives of knockout mice and positron emission temography in the development and evaluation of drugs
    • 批准号:
      12557007
    • 项目类别:
      Grant-in-Aid for Scientific Research (B)
    • 资助金额:
      $8.19万
    • 财政年份:
      2000
    • 负责人:
      YANAI Kazuhiko
    • 依托单位:
    海外基金