| Project/Area Number |
02557104
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | The Tokyo Metropolitan Institute of Medical Science |
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Principal Investigator |
SHINOZAKI Haruhiko The Tokyo Metropolitan Institute of Medical Science, Pharmacology, Head Researcher, 薬理, 研究員 (20109945)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIDA Michiko The Tokyo Metropolitan Institute of medical Science, Researcher, 東京都臨床医学総合研究所・薬理, 研究員 (90124437)
KWAK Shin National Institute of Neuroscience Researcher, 神経研究所, 室長 (40160981)
OHFUNE Yasufumi Suntory Institute of Bioorganic Research, Researcher, サントリー生物有機科学研究所, 研究員 (20142078)
SHINOZAKI Haruhiko The Tokyo Metropolitan Institute of Medical Science, Pharmacology, Head Research (20109945)
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| Project Period (FY) |
1990 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥12,000,000 (Direct Cost: ¥12,000,000)
Fiscal Year 1991: ¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 1990: ¥6,700,000 (Direct Cost: ¥6,700,000)
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| Keywords | Glutamate / Metabotropic glutamate receptor / presynaptic inhibition / monosynaptic reflex / Neuron damage / NMDA antagonist / カイニン酸 / アクロメリン酸 / cーfos / 興奮性アミノ酸 / 片側半球壊死 / 脳虚血 |
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| Research Abstract |
L-CCG-I, a potent metabotropic glutamate receptor agonist, potentiated markedly the presynaptic inhibition in the isolated newborn rat spinal cord preparation, preferentially depressing monosynaptic reflexes induced by electrical stimulation of the dorsal root fibres. The depression of monosynaptic reflexes by L-CCG-I was caused in concentrations wen below those which did not cause postsynaptic depolarization. This inhibitory action of L-CCG-I is somewhat different from that of trans-ACPD, another metabotropic glutamate receptor agonist. The inhibitory action of L-CCG-I is not depressed by any known pharmacological agents. When this drug was asministered into the ventricule, generalized muscle relaxtant actions were observed in the rat. When L-CCG-L and trans-ACPD were injected into the lateral ventricule, cortex, and hippocampus, they did not induce neuronal damage in these areas. In the mongolian gerbil, ischemic neuronal damage was considerably blocked by pretreatmefnt with intraventricular L-CCG I. These experimental data suggest that the metabotropic glutamate receptor agonist may be useful for the prevention of neuronal damage.
An interesting compound has been succeeded in, synthesis by a group of the Tohoku University. This compound has been knwon as an endogenous one, but the pharmacological and physiological actions have been unknown. This compound demonstrated to be a considerably potent NMDA antagonist, and its activity was about 20 times lower than that of CPP. However, NMDA receptors have been believed to be related to neuronal death induced by excitatory amino acids, therefore, it is of great interest to examine the physiological function of this compound in the body.
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