PHARMACOLOGICAL REGULATION OF NGF BIOSYNTHESIS

NGF生物合成的药理学调控

• 批准号: 2259729
• 负责人: Italo Mocchetti
• 金额: $ 6.75万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-08-01 至 1998-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2259729
• 关键词: PC12 cells; aging; beta adrenergic receptor; cerebral cortex; choline acetyltransferase; cholinergic receptors; cyclic AMP; dexamethasone; dihydrotestosterone; enzyme induction /repression; genetic enhancer element; genetic promoter element; glioma; growth factor receptors; hormone regulation /control mechanism; laboratory rat; neuropharmacology; neurotrophic factors; norepinephrine; protein biosynthesis; protein kinase C; receptor expression; tissue /cell culture; transcription factor

We have demonstrated that the activation of beta-adrenergic receptors (BAR) by the lipophilic BAR agonist clenbuterol increases NGF biosynthesis in rat cerebral cortex and in C6-2B glioma cells (glial phenotype). The increase in NGF mRNA is due to increased gene expression. I will extend these studies by using various BAR agonists and antagonists (acute or protracted treatments) in adult and 2 year old rats. Neuroanatomical correlates will be used to establish whether NGF, induced pharmacologically, exerts physiological effects. C6-2B rat glioma cells will be used to characterize signal transduction mechanisms (activation of protein kinases A and C) and steroid receptors operative in the regulation of NGF biosynthesis in glial cells. These studies will be complemented by experiments aimed to test whether transcriptional factors which contribute to the tissue specific regulation of NGF expression, are induced or activated (following the proposed pharmacological manipulations) in glial and/or neuronal cells.

我们已经证明了β-肾上腺素能受体的激活 （bar）由亲脂性棒激动剂clenbuterol增加NGF 大鼠脑皮质和C6-2B神经胶质瘤细胞中的生物合成（神经胶质 表型）。 NGF mRNA的增加是由于基因增加 表达。 我将通过使用各种酒吧激动剂来扩展这些研究 成人和2岁的拮抗剂（急性或长期治疗） 老鼠。 神经解剖学相关性将用于确定NGF是否 诱导的药理学会发挥生理作用。 C6-2B大鼠 神经胶质瘤细胞将用于表征信号转导机制 （蛋白激酶A和C的激活）和类固醇受体的手术 在调节神经胶质细胞中NGF生物合成的过程中。 这些研究会 通过旨在测试转录的实验补充 有助于组织特异性调节NGF的因素 表达，诱导或激活（遵循提出的 在神经胶质和/或神经元细胞中的药理操作）。