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CELLULAR MECHANISMS OF NEUROENDOCRINE HORMONE SECRETION

神经内分泌激素分泌的细胞机制

基本信息

批准号：
6624811
负责人：
NANCY L WAYNE
金额：
$ 19.42万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
1994
资助国家：
美国
起止时间：
1994-12-01 至 2004-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6624811
关键词：
Aplysia calcium flux calmodulin dependent protein kinase hormone biosynthesis hormone regulation /control mechanism invertebrate endocrinology invertebrate hormone membrane potentials neuroendocrine system neurohormones neuropharmacology neuroregulation neurotransmitter transport protein kinase A protein kinase C radioimmunoassay reproductive hormone secretion

项目摘要

DESCRIPTION (applicant's abstract): Release of transmitters and hormones from neurons plays a critical role in transmission of information between neighboring cells and distant tissues. Revealing mechanisms that control neurosecretion is vital to our understanding of both homeostasis of a wide variety of physiological systems and disease processes that occur when this transmission breaks down. Our long-term goal is to understand neural control of peptide secretion and its impact on physiology and behavior. The broad aim of this proposal is to reveal and study underlying cellular and molecular events regulating synthesis and secretion of a neurohormone (egg laying hormone, ELH) using the bag cell neurons of Aplysia as a model system. We are now able to monitor membrane excitability and ELH secretion from bag cell neurons of freely-behaving animals, from bag cell neurons in excised neural tissue maintained in vitro, and from single bag cell neurons in culture. This gives us a relatively unique ability to move between studies addressing molecular and cell physiological issues and those addressing systems and behavioral questions using a single neuroendocrine system. There are three specific aims of this proposal. The first aim is to determine the role of calcium from intracellular stores in regulating the pattern of ELH secretion. We will use electrophysiology, calcium imaging, and RIA measurement of hormone secretion to determine the pattern of intracellular calcium in response to electrical afterdischarge, the effects of manipulating intracellular calcium on ELH secretion, and the source of intracellular calcium controlling ELH secretion in response to afterdischarge. The second aim is to investigate protein kinase A (PKA), protein kinase C (PKC), and CaM kinase in bag cell neurons. We plan to monitor kinase activities using both a traditional radiolabeling approach, as well as newly developed optical imaging techniques. In addition, we will investigate the role of CaM kinase II in regulating ELH secretion. The third specific aim is to understand cellular and molecular events that mediate the stimulatory effects of afterdischarge on ELH biosynthesis. We will investigate the effects of afterdischarge on specific steps along the translation pathway, and the roles of the calcium, PKA and PKC signaling pathways in regulating specific translational events leading to alterations in ELH biosynthesis. The outcome of this work should enable us to develop a detailed model of cellular mechanisms that link membrane excitation to neurohormone secretion and neurohormone synthesis.

描述(申请人摘要)：释放递质和激素神经元在信息传递中起着至关重要的作用邻近的细胞和远处的组织。揭示了控制神经分泌对于我们理解广泛的当发生这种情况时，会发生各种生理系统和疾病过程传输中断。我们的长期目标是了解神经控制多肽分泌及其对生理和行为的影响。的广泛目标这项提议是为了揭示和研究潜在的细胞和分子事件。调节神经激素(产卵激素，ELH)的合成和分泌以海兔袋状细胞神经元为模型系统。我们现在能够监测BAG细胞神经元膜兴奋性和ELH分泌自由活动的动物，来自切除的神经组织中的袋状细胞神经元在体外保持，并从单袋细胞培养神经元。这给了我们一种相对独特的能力，可以在解决分子和细胞生理问题以及解决系统和行为问题的问题使用单一的神经内分泌系统。这有三个具体目标求婚。第一个目标是确定细胞内钙的作用。储存在调节ELH的分泌模式中。我们将使用电生理学、钙成像和激素分泌的RIA测量测定细胞内钙离子对电刺激的反应模式后放电、细胞内钙调控对ELH的影响分泌，以及控制ELH分泌的细胞内钙的来源对后放电的反应。第二个目标是研究蛋白激酶A 蛋白激酶C(PKC)和钙调素激酶(CaM)在BAG细胞神经元中表达。我们计划使用传统的放射性标记方法监测激酶活性，如以及新开发的光学成像技术。此外，我们还将研究CaM激酶II在调节ELH分泌中的作用。第三具体目的是了解细胞和分子事件，这些事件介导了后放电对ELH生物合成的刺激作用。我们会调查的后放电对翻译路径上特定步骤的影响，钙、PKA和PKC信号通路在调控中的作用导致ELH生物合成改变的特定翻译事件。这个这项工作的结果应该使我们能够开发一个详细的细胞模型将膜兴奋与神经激素分泌和神经激素的合成。