课题基金 / 基金详情

Design and development of excitatory amino acid related compounds for protection against senile neuronal death

Design and development of excitatory amino acid related compounds for protection against senile neuronal death
设计和开发用于预防老年神经元死亡的兴奋性氨基酸相关化合物
批准号:
05557113
负责人:
SHINOZAKI Haruhiko
金额:
$7.17万
依托单位国家:
日本
项目类别:
Grant-in-Aid for Developmental Scientific Research (B)
财政年份:
1993
资助国家:
日本
项目状态:
已结题
起止时间:
1993 至 1994

项目摘要

项目成果

SHINOZAKI Haruhiko的其他基金

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相关文献

中文摘要
翻译
Potent agonist for metabotropic glutamate receptors,such as L-CCG-I,DCG-IV,cis-MCG-I and trans-MCG-I were found in the present study.All of them are derivatives of2-(Carboxyclopropyl)glycine(CCG),which provided useful information about relationship between activation of glutamate receptors and conformation of agonists.Their conformation of glutamate skeleton is an extended form,and they reduced monosynaptic excitation in the isolated newborn rat spinal cord,by inhibiting transmitter release from nerve terminal.These four agonists for metabotropic glutamate receptors inhibited forskolin-stimulated cyclic AMP content in a dose dependent manner,and they demonstrated potent CNS depressant actions in the rat.Among them DCG-IV was the most potent.Pharmacological actions of our newly developed agonists for metabotropic glutamate receptors were clarified with special reference to kainate excitotoxicity.Intraventricular DCG-I·V caused selective neuron damage at relatively high doses in the cingulate cortex and the hippocampal subiculum in the rat,but other agonists did not cause neuron damage in the rat.DCG-IV considerably alleviated the kainate-induced limbic seizures。At relatively low doses,DCG-IV protected some kinds of neurons in the hippocampal CA3 and the amygdala against kainate neurotoxicity,when intraventricularly injected to the rat.These new agonists would provide useful probe for elucidating the mechanism underlying neuron damage induced by excitatory amino acids.
英文摘要
Potent agonist for metabotropic glutamate receptors, such as L-CCG-I,DCG-IV,cis-MCG-I and trans-MCG-I were found in the present study. All of them are derivatives of 2- (carboxycyclopropyl) glycine (CCG), which provided useful information about relationship between activation of glutamate receptors and conformation of agonists. Their conformation of glutamate skeleton is an extended form, and they reduced monosynaptic excitation in the isolated newborn rat spinal cord, by inhibiting transmitter release from nerve terminal. These four agonists for metabotropic glutamate receptors inhibited forskolin-stimulated cyclic AMP content in a dose dependent manner, and they demonstrated potent CNS depressant actions in the rat. Among them DCG-IV was the most potent. Pharmacological actions of our newly developed agonists for metabotropic glutamate receptors were clarified with special reference to kainate excitotoxicity. Intraventricular DCG-I・V caused selective neuron damage at relatively high doses in the cingulate cortex and the hippocampal subiculum in the rat, but other agonists did not cause neuron damage in the rat.DCG-IV considerably alleviated the kainate-induced limbic seizures. At relatively low doses, DCG-IV protected some kinds of neurons in the hippocampal CA3 and the amygdala against kainate neurotoxicity, when intraventricularly injected to the rat. These new agonists would provide useful probe for elucidating the mechanism underlying neuron damage induced by excitatory amino acids.
期刊论文(97)
专著(0)
科研奖励(0)
会议论文
篠崎温彦: "興奮性アミノ酸神経伝達物質とパーキンソン病" 細胞工学. 12. 807-812 (1993)
Atsuhiko Shinozaki:“兴奋性氨基酸神经递质和帕金森病”细胞工程 12. 807-812 (1993)。
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通讯作者:
Ohfune, Y.et al.: "Synthesis of L-2-(2,3-dicarboxycyclopropyl)glycines. Novel conformationally restricted glutamate analogues." Bioorganic & Medi.Chem.Lett.3. 15-18 (1993)
Ohfune, Y.等人:“L-2-(2,3-二羧基环丙基)甘氨酸的合成。新型构象限制的谷氨酸类似物。”
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通讯作者:
Shinozaki, H.et al.: "Excitatory amino acids : physiological and pharmacological probes for neuroscience research." Acta.Neurobiol.Exp.53. 43-52 (1993)
Shinozaki, H.et al.:“兴奋性氨基酸:神经科学研究的生理学和药理学探针。”
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通讯作者:
Ohfune, Y.et al.: "L-2-(Carboxycyclopropyl)glycines ; Conformationally constrained L-glutamate analogues." Drug design for neuroscience. 261-283 (1993)
Ohfune, Y. 等人:“L-2-(羧基环丙基)甘氨酸;构象受限的 L-谷氨酸类似物。”
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通讯作者:
70
    Pharmacological probes for elucidating the physiological role of glutamate receptors
    Design and development of agonists for metabotropic glutamate receptors to protect against neuronal death
    Animal models for amiotrophic lateral screrolis induced by an excitatory amino acid, acromelic acid.
    Drug Design and Development of Glutamate Blockers which protect against Neuronal Death.
    海外基金