β-Adrenoceptor up-regulation and intracellular signal transduction systems

β-肾上腺素受体上调和细胞内信号转导系统

• 批准号: 13670105
• 负责人: OHKUMA Seitaro
• 金额: $ 0.83万
• 依托单位: KAWASAKI MEDICAL SCHOOL
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670105/
• 关键词: β-adrenoceptors; up-regulation; nadolol; [3H] CGP-12177 binding; adenylate cyclase; cerebrocortical neurons; β-arrestin; 3H]CGP-12177結合; [^3H]CGP-12177結合

In this research project, we attempted to investigate alterations in intracellular signal transduction systems coupling to β-adrenoceptors (β-AR) in association with β-AR up-regulationAt first, we confirmed that mouse cerebral cortical neurons in primary culture used had both β1- and β2-AR coupling to Camp generating system. Sustained exposure to nadolol induced a maximal increase of [3H] CGP-12177 binding after 6 hr of the exposure and increased both β-AR expressions on neuronal membrane. On the other hand, increased expression of mRNA of these eceptor was found 12 hr after the exposure. The increased receptor expression on neuronal membrane was due to increased translocation of receptor proteins from cytosol to membrane, and synthesis of receptor proteins did not participate in these events. After the expression of receptor mRNA increased, the expendent on synthesis of the proteinsIn association with β-AR up-regulation, forskolin-evoled formation of Camp increased. Among adenylate cyclase (AC) isozymes present in the neurons, only type I was found to increase significantly accompanying with β-AR up-regulation. In addition, β-AR up-regulation

在本研究项目中，我们试图研究与β-肾上腺素受体（β-AR）偶联的细胞内信号转导系统的改变与β-AR上调的关系。首先，我们证实了原代培养的小鼠大脑皮质神经元与Camp生成系统同时具有β1-和β2-AR偶联。持续暴露于纳多洛尔后，6小时后[3H] CGP-12177结合量最大，神经元膜上β-AR表达增加。另一方面，暴露12小时后发现这些受体mRNA的表达增加。神经元膜上受体表达的增加是由于受体蛋白从细胞质向膜的易位增加，而受体蛋白的合成不参与这些事件。受体mRNA表达增加后，与β-AR上调相关的蛋白合成消耗增加，forskolin进化的Camp形成增加。在神经元中存在的腺苷酸环化酶（AC）同工酶中，只有I型随β-AR上调而显著增加。此外，β-AR上调

项目成果

Katsura, M., et al.: "NMDA receptor activation enhances diazepam binding inhibitor mRNA expression in mouse cerebral cortical neurons"Mol.Brain Res.. 88. 161-165 (2001)

Katsura，M.，等人：“NMDA 受体激活增强小鼠大脑皮层神经元中地西泮结合抑制剂 mRNA 表达”Mol.Brain Res.. 88. 161-165 (2001)

Katsura, M., et al.: "Up-regulation of L-type volgage-dependent calcium channels after long term exposure to nicotine in cerebral cortical neurons"J.Biol.Chem.. 277. 7979-7988 (2002)

Katsura, M., 等人：“大脑皮层神经元长期暴露于尼古丁后 L 型电压依赖性钙通道的上调”J.Biol.Chem.. 277. 7979-7988 (2002)

Katsura, M., et al.: "Functional significance of nitric oxide in ionomycin-induced [3H]GABA release from mouse cerebral cortical neurons"J. Neurochem.. 81. 130-141 (2002)

Katsura, M., 等人：“一氧化氮在离子霉素诱导的小鼠大脑皮层神经元释放 [3H]GABA 中的功能意义”J.

Ohkuma, S., et al.: "Peroxynitrite affects Ca2+influx through voltage-dependent calcium channels"J. Neurochem.. 76. 341-350 (2001)

Ohkuma, S. 等人：“过氧亚硝酸盐通过电压依赖性钙通道影响 Ca2 流入”J。

Suwaki, H. et al.: "Recent research on alcohol tolerance and depencence"Alcohol.Clin.Exp.Res.. 25. 189S-196S (2001)

Suwaki, H. 等人：“酒精耐受性和依赖性的最新研究”Alcohol.Clin.Exp.Res.. 25. 189S-196S (2001)