REGULATION OF NEUROPEPTIDE BIOSYNTHESIS AND SECRETION

神经肽生物合成和分泌的调节

• 批准号: 2036400
• 负责人: VICTOR MAY
• 金额: $ 7.43万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-12-15 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2036400
• 关键词: ascorbate; calcium flux; catecholamines; cell cell interaction; gene induction /repression; glucocorticoids; immunocytochemistry; immunoelectron microscopy; in situ hybridization; laboratory rat; mixed tissue /cell culture; neural plasticity; neuropeptide Y; neuropeptide receptor; neuropharmacology; neurotransmitter biosynthesis; norepinephrine; northern blottings; phenotype; second messengers; secretion; superior cervical ganglion

The goal of this study is to determine the central regulators of neuronal function using cultured superior cervical ganglion (SCG) neurons as models. The focus of this proposal is to examine the regulatory interrelationship between neuronal peptide and classical transmitter expression, and in particular, the expression of neuropeptide Y (NPY) and catecholamines (CA) in the SCG. Several questions examining the factors and environmental cues that coordinately or independently regulate SCG NPY and catecholamine (CA) expression will be addressed, including (1) What are the regulators of neuronal NPY expression? (2) Are NPY and CA expression altered by the same regulatory factors? (3) How does neuronal phenotype affect NPY expression? (4) Do specific target tissues regulate neuronal NPY expression? (5) What are the cellular mechanisms of altered neuropeptide expression? Several parameters will be used to characterize culture NPY/CA content and biosynthesis including radioimmunoassay, biosynthetic labeling techniques, Northern blot analysis, and HPLC/electrochemical detection techniques. The effects of neuronal input onto SCG cells, that is stimulation of second messenger system, calcium flux, depolarization, and specific receptor- mediated stimulation on SCG NPY production will be examined and correlated to CA production levels. How factors that change SCG neurotransmitter expression from catecholaminergic to cholinergic phenotype alter NPY expression will be examined. In coculture studies, the effects of SCG target cells on neurotransmitter/neuropeptide expression will be determined. These studies will have significant implications in establishing how complex and integrated signals direct normal neuronal development and physiological functions.

本研究的目的是确定神经元的中枢调节因子 使用培养的颈上神经节（SCG）神经元作为模型来研究功能。 该提案的重点是审查监管之间的相互关系 神经元肽和经典递质表达之间，以及 特别是神经肽 Y (NPY) 和儿茶酚胺 (CA) 的表达 在SCG中。 检查因素和环境线索的几个问题 协调或独立调节 SCG NPY 和儿茶酚胺 (CA) 表达将被解决，包括（1）监管机构是什么 神经元NPY表达？ (2) NPY 和 CA 表达是否受到相同的影响 监管因素？ (3)神经元表型如何影响NPY表达？ (4) 特定靶组织是否调节神经元NPY表达？ (5) 什么 神经肽表达改变的细胞机制是什么？ 一些 参数将用于表征培养物 NPY/CA 含量和 生物合成，包括放射免疫分析、生物合成标记技术、 Northern 印迹分析和 HPLC/电化学检测技术。 这 神经元输入对 SCG 细胞的影响，即刺激第二 信使系统、钙通量、去极化和特定受体- 将检查和关联对 SCG NPY 产生的介导刺激 达到 CA 生产水平。 影响SCG神经递质的因素 从儿茶酚胺能表型到胆碱能表型的表达改变 NPY 将检查表达。 在共培养研究中，SCG 的影响 神经递质/神经肽表达的靶细胞将是 决定。 这些研究将产生重大影响 确定复杂和集成的信号如何引导正常神经元 发育和生理功能。