Neuropeptide Y and the Control of Catecholamine Secretion from the Adrenal Gland

神经肽 Y 和肾上腺儿茶酚胺分泌的控制

• 批准号: 7799041
• 负责人: MATTHEW WHIM
• 金额: $ 21.11万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-06 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7799041
• 关键词: Address; Adrenal Glands; Adrenal Medulla; Adrenal hormone preparation; Affect; Blood; Blood Pressure; Cardiovascular Diseases; Cardiovascular system; Catecholamines; Cells; Chromaffin Cells; Cytoplasmic Granules; Disease; Electrophysiology (science); Endocrine; Epinephrine; Feedback; Gland; Hormones; Hypertension; Image; In Situ; In Vitro; Knock-out; Mediating; Metabolic Control; Molecular; Mus; Musculoskeletal; Nature; Neurons; Neurotransmitters; Norepinephrine; Organ; Organism; Pathway interactions; Pattern; Play; Preparation; RNA Interference; Receptor Activation; Regulation; Reverse Transcriptase Polymerase Chain Reaction; Role; Slice; Spinal Cord; Surface; Sympathetic Nervous System; Synapses; System; Techniques; Testing; Tissues; Work; autocrine; cell type; cholinergic neuron; controlled release; excitatory neuron; fighting; meetings; neuropeptide Y; novel; polypeptide; presynaptic; public health relevance; receptor; relating to nervous system; research study; respiratory; response; therapy development; voltage

DESCRIPTION (provided by applicant): The inner region of the mammalian adrenal gland is composed of sympathetic neurons that release the catecholamine hormones, epinephrine and norepinephrine, into the blood. During the fight-or-flight response, these hormones are released from the adrenal gland and prime the organism for the sudden demands that may be placed upon the circulatory, respiratory, musculoskeletal and metabolic control systems. Consistent with their wide-reaching actions, the inappropriate activity of the adrenal gland has been associated with a variety of diseases including hypertension. The long-term objective of the proposed study is to determine the mechanisms that normally control the release of these adrenal hormones. One control pathway is believed to involve the secretion of transmitters that are co-released with the catecholamines and that mediate "short feedback loops" within the gland itself. The identity of these co-transmitters and the condition(s) under which they released are not clear. However one strong candidate is neuropeptide Y, a polypeptide that is synthesized by chromaffin cells. Our hypothesis is that neuropeptide Y is an adrenal neurotransmitter whose release mediates short feedback loops that regulate catecholamine secretion. To test this hypothesis we have 3 specific aims that we will address using murine sympathetic neurons (chromaffin cells) and adrenal slices. In the first set of experiments we will test the hypothesis that the net effect of NPY is to increase the secretion of the catecholamines. Our second specific aim is to test the hypothesis that the release of NPY can regulate catecholamine secretion in an autocrine (cell-limited) manner. In the third set of experiments we will test the hypothesis that NPY can also regulate catecholamine secretion by altering the strength of the pre-synaptic input that normally limits catecholamine secretion. By using in vitro and in situ preparations and by employing electrophysiological and molecular techniques we will comprehensively determine whether local feedback pathways control catecholamine secretion. Although this work examines the regulation of the adrenal gland, similar mechanisms are likely to control the release of hormones from many different types of endocrine tissue. PUBLIC HEALTH RELEVANCE: The inner region of the adrenal gland secretes hormones that regulate blood pressure and the cardiovascular system. Understanding how the release of these molecules is controlled is needed for the development of treatments that could correct their inappropriate or excessive release.

描述（由申请人提供）：哺乳动物肾上腺的内部区域由交感神经元组成，这些神经元将儿茶酚胺激素，肾上腺素和去甲肾上腺素释放到血液中。在战斗或飞行的反应中，这些激素从肾上腺中释放出来，并为生物体奠定了突然的需求，这可能会放在循环系统，呼吸道，肌肉骨骼和代谢控制系统上。与其广泛的行动一致，肾上腺的不适当活动与包括高血压在内的多种疾病有关。拟议研究的长期目标是确定通常控制这些肾上腺激素释放的机制。据信，一种控制途径涉及与儿茶酚胺共同发行的发射器的分泌，并介导腺体内的“短反馈回路”。这些共递发送者的身份及其释放的状况尚不清楚。但是，一个有力的候选者是神经肽Y，这是由铬蛋白细胞合成的多肽。我们的假设是，神经肽Y是肾上腺神经递质，其释放介导了调节儿茶酚胺分泌的短反馈环。为了检验这一假设，我们有3个特定的目标，我们将使用鼠交感神经元（铬蛋白细胞）和肾上腺切片来解决。在第一组实验中，我们将检验以下假设：NPY的净效应是增加儿茶酚胺的分泌。我们的第二个具体目的是检验以下假设：NPY的释放可以以自分泌（细胞限制）方式调节儿茶酚胺分泌。在第三组实验中，我们将测试以下假设：NPY还可以通过改变通常限制儿茶酚胺分泌的突触前输入的强度来调节儿茶酚胺分泌。通过使用体外和原位制剂，并采用电生理和分子技术，我们将全面确定局部反馈途径是否控制着儿茶酚胺分泌。尽管这项工作检查了肾上腺的调节，但类似的机制可能会控制许多不同类型的内分泌组织中激素的释放。公共卫生相关性：肾上腺的内部区域分泌调节血压和心血管系统的激素。了解这些分子的释放是如何控制的，以开发可以纠正其不适当或过度释放的治疗方法。