2000 Fiscal Year Final Research Report Summary
Nociceptin receptor antagonist
| Project/Area Number |
11559005
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
広領域
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| Research Institution | Institute of Life Science, Kurume University (2000)
The University of Tokyo (1999) |
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Principal Investigator |
TAKESHIMA Hiroshi Institute of Life Science, Kurume University, 分子生命科学研究所, 教授 (70212024)
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| Co-Investigator(Kenkyū-buntansha) |
OHTA Hisashi Banyu Pharmaceutical Co., LTD., 研究所, 研究員
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| Project Period (FY) |
1999 – 2000
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| Keywords | nociceptin / nociceptin receptor / opioids / opioid receptors |
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| Research Abstract |
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.
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[Publications] Ahmadi, S., Kotalla, C., Guhring, H., Takeshima, H., Pahl, A.& Zeilhofer, H.U.: "Modulation of synaptic transmission by nociceptin/orphanin FQ and nocistatin in the spinal cord dorsal horn of mutant mice lacking the nociceptin/orphanin FQ receptor."Mol. Pharmacol.. (in press).
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[Publications] Houtani, T., Nishi, M., Takeshima, H., Sato, K., Sakuma, S., Kakimoto, S., Ueyama, T., Noda, T.& Sugimoto, T.: "Distribution of nociceptin/orphanin FQ precursor protein and receptor in brain and spinal cord."J.Comp. Neurol.. 424. 489-508 (2000)
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[Publications] Noda, Y., Mamiya, T., Manabe, T., Nishi, M., Takeshima, H.& Nabeshima, T.: "Role of nociceptin systems in learning and memory."Peptides. 21. 1063-1069 (2000)
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[Publications] Inoue, M., Shimohira, I., Yoshida, A., Zimmer, A., Takeshima, H., Sakurada, T.& Ueda, H.: "Dose- related opposite modulation by nociceptin/orphanin FQ of substance P nociception in the nociceptors and spinal cord."J.Pharmacol. Exp. Ther.. 291. 308-313 (1999)
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