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.

拟议研究的长期目标是了解肽 神经元活动调节的神经递质机制和 自主功能和行为的调节。 我们使用作为例子 海洋软体动物海兔，可以对机制进行详细分析 细胞和分子水平。 研究主要在我们的实验室进行 已确定神经内分泌袋细胞是多递质 该系统释放源自共同前体蛋白的 4 种肽。 这些肽用于调节位于其附近的神经元的活动 中枢神经系统和袋子本身。 这些调节作用 可持续长达几个小时，被认为可以调节内脏运动 以及在复杂的遗传过程中发生的行为变化 预定行为，产蛋。 袋细胞的作用之一是 抑制某些已识别的目标神经元超过两个小时。 我们 最近纯化并部分表征了一种新的肽 腹部神经节模仿这种长时间的抑制。 部分氨基 酸序列分析表明该肽与脊椎动物同源 脑肠肽家族。 另外两种新型神经肽也已被 分离并部分表征。 我们计划使用生化、重组DNA和免疫细胞化学 技术进一步定义这些功能的分子基础 神经肽。 我们将使用重组DNA技术来分离和 对编码抑制肽的基因进行测序。 我们还计划 确定肽是否从神经元中释放并描述 肽在中枢神经系统内的分布。 相似的 计划对另外两种新型神经肽进行研究。 这 拟议的调查，结合正在进行的功能和行为 研究，可能会导致对基本机制有更清晰的了解 神经元之间的化学信号传导，神经肽的进化 结构和功能，以及遗传的细胞基础 预定的或“本能的”行为。