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Nociceptin receptor antagonist

伤害感受肽受体拮抗剂

基本信息

批准号：
11559005
负责人：
TAKESHIMA Hiroshi
金额：
$ 9.15万
依托单位：
Institute of Life Science, Kurume University (2000)The University of Tokyo (1999)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11559005/
关键词：
nociceptin nociceptin receptor opioids opioid receptors

项目摘要

Our current studies have suggested that neuro-modulations mediated by the novel bioactive peptide named nociceptin or orphaninFQ regulate several signal-transmission pathways including pain, learning and memory and hearing. Based on our results, aims of this collaborative study were (i) attempt to identify chemical compounds acting antagonists for the nociceptin receptor, (ii) examination of such compounds as potent analgesics or memory stimulants in the whole animal level, and further (iii) analysis of physiological roles of neuro-modulations by the nociceptin system.Members in our collaborative team successfully found that chemical compounds, NalBenzH and J-113397, act as antagonists selectively for the nociceptin receptor. In our preliminary study comparing pharmacological responses of the compounds between wild-typec mice and mutant mice lacking the nociceptin receptor, they seemed to produce weak analgesic effects. However, to examine the possibility that they can be potent analgesics for broad- ranged pains or memory stimulants, we need to plan further animal-level studies. On the other hand, our collaborative studies have clarified the expression patterns of both the nociceptin precursor protein and nociceptin receptor in the central nervous system, the modulation of synaptic transmission by nociceptin in the dorsal horn of the spinal cord, the role of the nociceptin system during acquirement of morphine tolerance and dependence, and the nociceptin-mediated regulation of substanceP-induced pain responses.

我们目前的研究表明，由名为nociceptin或nociceptin FQ的新型生物活性肽介导的神经调节调节包括疼痛、学习记忆和听觉在内的多个信号传递途径。基于我们的研究结果，本合作研究的目的是（i）尝试鉴定作为伤害感受素受体拮抗剂的化合物，（ii）在整个动物水平上检查这些化合物作为有效的镇痛剂或记忆刺激剂，以及（iii）进一步分析伤害感受素系统的神经调节的生理作用。我们合作小组的成员成功地发现，NalBenzH和J-113397作为选择性的痛敏素受体拮抗剂。在我们的初步研究中，比较了野生型c小鼠和缺乏孤啡肽受体的突变小鼠之间的化合物的药理学反应，它们似乎产生弱的镇痛作用。然而，为了检验它们作为广泛疼痛的强效镇痛剂或记忆刺激剂的可能性，我们需要计划进一步的动物水平研究。另一方面，我们的合作研究阐明了痛敏素前体蛋白和痛敏素受体在中枢神经系统的表达模式，痛敏素对脊髓背角突触传递的调节，痛敏素系统在吗啡耐受和依赖获得过程中的作用，以及痛敏素介导的P物质痛反应的调节。