Development of selective ligands to histamine H3 and H4 receptors and its application to elucidate the physiological function of the receptors.
组胺 H3 和 H4 受体选择性配体的开发及其在阐明受体生理功能中的应用。
基本信息
- 批准号:15590225
- 负责人:
- 金额:$ 2.24万
- 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:2003
- 资助国家:日本
- 起止时间:2003 至 2005
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Histamine H4-receptor is the most recently discovered histamine receptor which has 35% overall homology to the H3-receptor. However, the tissue distribution of the two receptors is quite different. To elucidate the physiological and pathophysiological functions of the receptors, development of selective ligands to both receptors is indispensable. In this study, we synthesized a series of tetrahydrofuranylimidazole and tetrahydropyranylimidazole derivatives and examined the binding and functional activities on the receptors. Among them, we found two tetrahydrofuranylimidazoles as selective H4-agonists, OUP-13 and OUP-16, and two tetrahydropyranylimidazoles as selective H3-antagonists, OUP-152 and OUP-153.The H4-agonists inhibited histamine release form RBL-2H3 cells induced by low concentration of DNP-BSA antigen, indicating H4-receptor may regulate the allergic histamine release.In addition, we examined physiological function of the brain histaminergic system and found that central histamine participate in the transmission of taste information. Furthermore, we also found that a target of modafinil, a novel drug for narcolepsy, is the histaminergic system. This finding indicates that H3-antagonists may useful to treat narcolepsy.
组胺H4受体是最近发现的组胺受体,其与H3受体具有35%的总体同源性。然而,这两种受体的组织分布是完全不同的。为了阐明受体的生理和病理生理功能,开发两种受体的选择性配体是必不可少的。本研究合成了一系列四氢呋喃咪唑和四氢吡喃咪唑衍生物,并研究了它们与受体的结合和功能活性。其中,我们发现了两种选择性H4受体激动剂OUP-13和OUP-16,以及两种选择性H3受体拮抗剂OUP-152和OUP-153。H4受体激动剂抑制低浓度DNP-BSA抗原诱导的RBL-2 H3细胞组胺释放,表明H4受体可能调节过敏性组胺释放。此外,我们研究了大脑组胺能系统的生理功能,发现中枢组胺参与味觉信息的传递。此外,我们还发现,莫达非尼,一种新的嗜睡症的药物,靶点是组胺能系统。这一发现表明,H3-拮抗剂可用于治疗发作性睡病。
项目成果
期刊论文数量(35)
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.Hashimoto et al.: "Effect of H4-receptor ligands on IgE mediated histamine release from RBL-2H3 cells"J.Pharamacol.Sci.. 94(Suppl.1). 204 (2004)
T.Hashimoto 等人:“H4 受体配体对 IgE 介导的 RBL-2H3 细胞组胺释放的影响”J.Pharamacol.Sci.. 94(Suppl.1)。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Brain histamine and feeeding behavior (in Japanese)
脑组胺和进食行为(日语)
- DOI:
- 发表时间:2004
- 期刊:
- 影响因子:0
- 作者:T.Ishizuka;A.Yamatodani
- 通讯作者:A.Yamatodani
A Selective Human H4-Receptor Agonist : (-)-2-Cyano-1-methyl-3-{(2R,5R)-5-[1H-imidazol-4(5)-yl]tetrahydrofuran-2-yl}methylguanidine.
选择性人 H4 受体激动剂:(-)-2-氰基-1-甲基-3-{(2R,5R)-5-[1H-咪唑-4(5)-基]四氢呋喃-2-基}甲基胍
- DOI:
- 发表时间:2003
- 期刊:
- 影响因子:0
- 作者:T.Hashimoto;et al.
- 通讯作者:et al.
Pharmacophore model for histamine H3 receptor antagonist - microdialysis study -
组胺 H3 受体拮抗剂药效团模型 - 微透析研究 -
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:T.Fujita;et al.
- 通讯作者:et al.
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YAMATODANI Atsushi其他文献
YAMATODANI Atsushi的其他文献
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{{ truncateString('YAMATODANI Atsushi', 18)}}的其他基金
The role of histamine H4 receptor in the development of cancer-related fatigue
组胺 H4 受体在癌症相关性疲劳发生中的作用
- 批准号:
21590279 - 财政年份:2009
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Pathophysiological significance of inducible histamine in the brain.
大脑中诱导型组胺的病理生理学意义。
- 批准号:
10670141 - 财政年份:1998
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Development of the in vivo monitoring system of nitric oxide using a micro electrode.
使用微电极开发一氧化氮体内监测系统。
- 批准号:
07557019 - 财政年份:1995
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
Physiological significance of histamine H3-receptor as hetero-recetor in the brain.
组胺 H3 受体作为大脑异质受体的生理意义。
- 批准号:
07680843 - 财政年份:1995
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Cell Biological Compartmentation of Brain Histamine
脑组胺的细胞生物区室
- 批准号:
05670090 - 财政年份:1993
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for General Scientific Research (C)
Physiological significance of the histaminergic system : A brain microdialysis study using unanesthetized and freely-moving rats
组胺能系统的生理意义:使用未麻醉且自由活动的大鼠进行脑微透析研究
- 批准号:
02670085 - 财政年份:1990
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for General Scientific Research (C)
Histaminergic regulation of the neuroendocrine system: An analysis using microdialysis of the hypothalamus of conscious and freely moving rats.
神经内分泌系统的组胺能调节:使用微透析对有意识和自由活动的大鼠的下丘脑进行分析。
- 批准号:
63570128 - 财政年份:1988
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for General Scientific Research (C)
NEUROENDOCRINOLOGICAL ROLES OF HISTAMINE IN THE HYPOTHALAMO-HYPOPHYSEAL SYSTEM
组胺在下丘脑-垂体系统中的神经内分泌作用
- 批准号:
60480135 - 财政年份:1985
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for General Scientific Research (B)
An HPLC method for determination of dopamine, dopamine-3-O- and dopamine-4-O-sulfate in plasma, urine and tissues.
高效液相色谱法测定血浆、尿液和组织中的多巴胺、3-O-多巴胺和4-O-硫酸多巴胺。
- 批准号:
60870015 - 财政年份:1985
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Developmental Scientific Research
相似海外基金
The investigation of the association between the individual differences of histamine H3 receptor density and the cognitive function
组胺H3受体密度个体差异与认知功能的相关性研究
- 批准号:
26860957 - 财政年份:2014
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
Impact of histamine H3 receptor agents on PAE-induced synaptic plasticity deficits in dentate gyrus
组胺 H3 受体药物对 PAE 诱导的齿状回突触可塑性缺陷的影响
- 批准号:
10207335 - 财政年份:2014
- 资助金额:
$ 2.24万 - 项目类别:
Impact of histamine H3 receptor agents on PAE-induced synaptic plasticity deficits in dentate gyrus
组胺 H3 受体药物对 PAE 诱导的齿状回突触可塑性缺陷的影响
- 批准号:
10442640 - 财政年份:2014
- 资助金额:
$ 2.24万 - 项目类别:
Molecular bases for intracellular trafficking and functional signalosome formation mediated through histamine H3 receptor
通过组胺 H3 受体介导的细胞内运输和功能性信号体形成的分子基础
- 批准号:
26460331 - 财政年份:2014
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Impact of histamine H3 receptor agents on PAE-induced synaptic plasticity deficits in dentate gyrus
组胺 H3 受体药物对 PAE 诱导的齿状回突触可塑性缺陷的影响
- 批准号:
10674494 - 财政年份:2014
- 资助金额:
$ 2.24万 - 项目类别:
A new regulative mechanism for monoamine transporter expression in plasma membrane : The participation of histamine H3 receptor
质膜单胺转运蛋白表达的新调控机制:组胺H3受体的参与
- 批准号:
22592065 - 财政年份:2010
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Analysis of regulatory mechanisms of cell surface expression of Histamine H3 receptor
组胺H3受体细胞表面表达调控机制分析
- 批准号:
21590267 - 财政年份:2009
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
A study of regulation for monoamine transporter function via histamine H3 receptor
组胺H3受体调节单胺转运蛋白功能的研究
- 批准号:
19592141 - 财政年份:2007
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Physiological significance of histamine H3-receptor as hetero-recetor in the brain.
组胺 H3 受体作为大脑异质受体的生理意义。
- 批准号:
07680843 - 财政年份:1995
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Drug development with histamine H3 receptor as a target
以组胺H3受体为靶点的药物开发
- 批准号:
05557008 - 财政年份:1993
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Developmental Scientific Research (B)