Studies and development of agonists and antagonists of metabotropic glutamate receptors

代谢型谷氨酸受体激动剂和拮抗剂的研究与开发

• 批准号: 07558223
• 负责人: NAKANISHI Shigetada
• 金额: $ 2.3万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07558223/
• 关键词: metabotropic glutamate receptor1; agonist・antagonist; receptor-expressing cell; phenylglycine derivative; AMPA derivative; structure-activity relationship17GA01 : N.Sekiyama, et al.; アゴニスト; アンタゴニスト; アンダゴニスト

The metabotropic glutamate receptors (mGluRs) consist of 8 different subtypes. The aim of this research is to develop new agonists and antagonists of defferent mGluR subtypes by examining the agonistic and antagonistic effects of a large number of phenylglycine derivatives and other compounds on the signal transduction of representative mGluR1, mGluR2 and mGluR4/mGluR6 subtypes expressed in CHO cells. We have succeeded in developing new agonists and antagonists and have elucidated structure-activity relationships of these compounds for different mGluR subtypes.1.Our study of phenylglycine derivatives indicates that the nature and positions of side chains and ring substituents incorporated into the phenylglycine structure are critical in determining the agonist and antagonist activities of this group of compounds on different mGluR subtypes.2.alpha-Methylation produces different effects, depending on the chemical structures of lead compounds and on the subtype of mGluR tested.3.We have also demonstrated that new glutamate analogues such as 2-amino-4 (3-hydroxy-5-methylisoxazol-4-yl) butyric acid have agonist activities on mGluRs.

代谢型谷氨酸受体 (mGluR) 由 8 种不同的亚型组成。本研究的目的是通过研究大量苯基甘氨酸衍生物和其他化合物对 CHO 中表达的代表性 mGluR1、mGluR2 和 mGluR4/mGluR6 亚型信号转导的激动和拮抗作用，开发不同 mGluR 亚型的新激动剂和拮抗剂细胞。我们成功地开发了新的激动剂和拮抗剂，并阐明了这些化合物对于不同mGluR亚型的构效关系。1.我们对苯基甘氨酸衍生物的研究表明，纳入苯基甘氨酸结构的侧链和环取代基的性质和位置至关重要确定这组化合物对不同 mGluR 亚型的激动剂和拮抗剂活性。2.α-甲基化产生不同的作用，具体取决于先导化合物的化学结构和3.我们还证明了新的谷氨酸类似物，例如2-氨基-4（3-羟基-5-甲基异恶唑-4-基）丁酸对mGluR具有激动剂活性。

项目成果

Koki Moriyoshi, et al.: "Labeling neural cells using adenoviral gene transfer of membrane-targeted GFP." Neuron. 16. 255-260 (1996)

Koki Moriyoshi 等人：“利用膜靶向 GFP 的腺病毒基因转移来标记神经细胞。”

K.Moriyoshi, et al.: "Labelling neral cells using adenoviral gene transfer of membrane-targeted GFP." Neuron. 16. 255-260 (1996)

K.Moriyoshi 等人：“使用膜靶向 GFP 的腺病毒基因转移来标记神经细胞。”

K.Moriyoshi,et al.: "Labeling neural cells using adenoviral gene transfer of membrane-targeted GFP." Neuron. 16. 255-260 (1996)

K.Moriyoshi 等人：“利用膜靶向 GFP 的腺病毒基因转移来标记神经细胞。”

Masayuki Masu, et al.: "Specific deficit of the ON response in visual transmission by targeted disruption of the mGluR6 gene." Cell. 80. 757-765 (1995)

Masayuki Masu 等人：“通过靶向破坏 mGluR6 基因，导致视觉传输中 ON 响应的特定缺陷。”

Mineto Yokoi, et al.: "Refinement of odor molecule tuning by dendrodendritic synaptic inhibition in the olfactory bulb." Proceedings of the National Academy of Sciences of the United States of America. 92. 3371-3375 (1995)

Mineto Yokoi 等人：“通过嗅球中的树突突触抑制来细化气味分子调节。”