LOCALIZATION OF NEUROPEPTIDES AND RECEPTORS IN APLYSIA

海兔神经肽和受体的定位

• 批准号: 3738248
• 负责人: EARL MAYERI
• 金额: --
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3738248
• 关键词: Aplysia; alternatives to animals in research; autonomic nervous system; biological signal transduction; ganglions; immunocytochemistry; laboratory rabbit; neural inhibition; neural plasticity; neural transmission; neuroendocrine system; neurons; neuropeptide receptor; neuropeptides; nucleic acid sequence; protein sequence; recombinant DNA; synaptic vesicles; synaptogenesis; tissue /cell culture; western blottings

The long term goal of the proposed investigations is to understand peptide neurotransmitter mechanisms underlying modulation of neuronal activity and regulation of autonomic functions and behavior. We are using as an example the marine mollusk Aplysia which permits detailed analysis of mechanisms at the cellular and molecular levels. Studies done mainly in our laboratory have established that the neuroendocrine bag cells are a multitransmitter system that release 4 peptides derived from a common precursor protein. The peptides serve to modulate activity in neurons located near them in the central nervous system and in the bag themselves. These modulatory effects can last for up to several hours and are thought to regulate visceromotor and behavioral changes that occur during a complex, genetically predetermined behavior, egg laying. One effect of the bag cells is to inhibit certain identified target neurons for more than two hours. We recently purified and partially characterized a novel peptide from the abdominal ganglion that mimics this prolonged inhibition. Partial amino acid sequence analysis suggests the peptide is homologous to a vertebrate brain-gut peptide family. Two other novel neuropeptides have also been isolated and partially characterized. We plan to use biochemical, recombinant DNA and immunocytochemical techniques to further define the molecular basis of the functions of these neuropeptides. We will use recombinant DNA techniques to isolate and sequence the gene coding for the inhibitory peptide. We also plan to determine whether the peptide is released from neurons and to describe the distribution of the peptide within the central nervous system. Similar investigations are planned for the two other novel neuropeptides. The proposed investigations, combined with ongoing functional and behavioral studies, may result in a clearer understanding of fundamental mechanisms of chemical signalling between neurons, the evolution of neuropeptide structure and function, and the cellular basis of genetically predetermined, or "instinctive", behaviors.

拟议的调查的长期目标是了解肽 神经递质机制的神经元活性调节和 自主功能和行为的调节。 我们正在用作示例 海洋软体动物的Aplysia允许对机制进行详细分析 细胞和分子水平。 主要在我们的实验室进行的研究 已经确定神经内分泌袋细胞是多晶石器 释放从常见前体蛋白衍生的4种肽的系统。 肽用于调节其附近神经元的活性 中枢神经系统和袋子本身。 这些调节作用 可以持续多达几个小时，并被认为可以调节内脏运动 以及在复合物中发生的行为变化 预先确定的行为，卵子铺设。 袋单元的一种效果是 抑制某些已鉴定的靶神经元超过两个小时。 我们 最近纯化并部分表征了一种新型肽 模仿这种延长抑制作用的腹部神经节。 部分氨基 酸序列分析表明，肽与脊椎动物同源 脑肠肽家族。 另外两个新型神经肽也是 孤立和部分表征。 我们计划使用生化，重组DNA和免疫细胞化学 进一步定义这些功能的分子基础的技术 神经肽。 我们将使用重组DNA技术进行分离和 序列编码抑制性肽的基因。 我们还计划 确定肽是否是从神经元释放的，并描述 中枢神经系统中肽的分布。 相似的 计划针对另外两种新型神经肽进行研究。 这 拟议的调查，结合持续的功能和行为 研究可能会更清楚地了解 神经元之间的化学信号传导，神经肽的进化 结构和功能，以及遗传学的细胞基础 预定或“本能”行为。