MOLECULAR MECHANISM OF ADRENERGIC PLASTICITY

肾上腺素能可塑性的分子机制

• 批准号: 3413873
• 负责人: GALE Louise CRAVISO
• 金额: $ 14.27万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-09-01 至 1990-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3413873
• 关键词: chromaffin cells; enzyme mechanism; gene expression; genetic regulation; genetic translation; messenger RNA; muscarinic receptor; neural plasticity; nicotinic receptors; nucleic acid sequence; posttranslational modifications; protein biosynthesis; secretion; stimulant /agonist; tissue /cell culture; tyrosine

One of the basic principles important to the function of excitable neurosecretory cells is that the strength of synaptic activity modulates the secretory capacity of the cells. One of the best examples of this kind of biochemical neuroplasticity is the modulation of catecholamine synthesis which occurs in response to increased afferent neural activity in the peripheral and central nervous systems. In the peripheral nervous system, for example, both the short- and long-term activity of the rate-limiting enzyme in the catecholamine synthetic pathway, tyrosine hydroxylase, is modulated by cholinergic activity. In our previous studies, we focused on the short-term regulation of this enzyme using a convenient model system, isolated bovine adrenal chromaffin cells. Recently we have established that not only is short-term cholinergic regulation expressed in these cells, but also that the levels of tyrosine hydroxylase mRNA, and protein are modulated in response to cholinergic receptor occupancy. In the research presented in this application, we will utilize this in vitro induction of tyrosine hydroxylase levels by cholinergic agonists to understand and characterize the molecular mechanisms controlling the increased level of tyrosine hydroxylase mRNA and protein. We will determine the role of cholinergic receptor occupancy in regulating the level of tyrosine hydroxylase mRNA synthesis and the translation of this message into tyrosine hydroxylase enzyme protein. We will establish the basis for the temporal disparity between the time course of the increase in message level and the increase in tyrosine hydroxylase enzyme activity. Lastly, we will evaluate the role of ribonucleotide sequences within the untranslated region of tyrosine, hydroxylase mRNA in influencing the translation efficiency of the tyrosine hydroxylase message.

兴奋性神经元功能的一个重要基本原则是 突触活动的强度调节神经分泌细胞 细胞的分泌能力。这方面最好的例子之一 一种生化神经可塑性是儿茶酚胺的调节 合成，其响应于传入神经活动增加而发生 在外周和中枢神经系统中。外周神经 例如，系统的短期和长期活动 儿茶酚胺合成途径中的限速酶，酪氨酸 羟化酶的活性受胆碱能活性调节。在我们以前 研究中，我们专注于这种酶的短期调节， 方便的模型系统，分离的牛肾上腺嗜铬细胞。 最近，我们已经确定，不仅是短期胆碱能 调节在这些细胞中表达，而且， 酪氨酸羟化酶mRNA和蛋白质的调节， 胆碱能受体占有率 在本申请中提出的研究中，我们将利用它， 胆碱能激动剂对酪氨酸羟化酶水平的体外诱导 了解和表征控制的分子机制， 酪氨酸羟化酶mRNA和蛋白水平升高。我们将 确定胆碱能受体占有率在调节 酪氨酸羟化酶mRNA合成水平及其翻译 信息转化为酪氨酸羟化酶蛋白。我们将建立 增加的时间进程之间的时间差异的依据 酪氨酸羟化酶的增加 活动最后，我们将评估核糖核苷酸序列的作用 在酪氨酸的非翻译区内， 影响酪氨酸羟化酶的翻译效率 留言该