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: 7631586
• 负责人: MATTHEW WHIM
• 金额: $ 10.35万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-23 至 2009-04-05
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7631586
• 关键词: Address; Adrenal Glands; Adrenal Medulla; Adrenal hormone preparation; Affect; Blood; Cardiovascular Diseases; Cardiovascular system; Catecholamines; Cells; Chromaffin Cells; Condition; 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; neuropeptide Y; novel; polypeptide; presynaptic; receptor; relating to nervous system; research study; respiratory; response; voltage

PROJECT SUMMARY. 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 arise from 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.

项目摘要。 哺乳动物肾上腺的内部区域由交感神经元组成 期间将儿茶酚胺激素肾上腺素和去甲肾上腺素释放到血液中。 在战斗或逃跑反应中，这些激素从肾上腺释放并启动 生物体可能对循环系统、呼吸系统、 与其广泛的作用一致，肌肉骨骼和代谢控制系统。 肾上腺活动不当与多种疾病有关 包括高血压。 拟议研究的长期目标是确定机制 据信，通常控制这些肾上腺激素的释放。 由与儿茶酚胺共同释放的递质的分泌产生，并且 调解 ¿短反馈循环¿这些共同递质的身份和 他们释放的条件尚不清楚，但有一位强有力的候选人。 神经肽Y，一种由嗜铬细胞合成的多肽。 我们的假设是神经肽 Y 是一种肾上腺神经递质，其 释放介导调节儿茶酚胺分泌的短反馈回路来测试这一点。 假设我们有 3 个具体目标，我们将使用小鼠交感神经元来解决这些目标 （嗜铬细胞）和肾上腺切片在第一组实验中，我们将检验假设。 NPY 的净效应是增加儿茶酚胺的分泌。 具体目的是检验NPY的释放可以调节儿茶酚胺的假设 在第三组实验中，我们将测试以自分泌（细胞限制）方式的分泌。 假设 NPY 还可以通过改变儿茶酚胺的强度来调节儿茶酚胺的分泌 通常限制儿茶酚胺分泌的突触前输入通过体外和原位使用。 准备工作并通过采用电生理学和分子技术，我们将 综合判断局部反馈通路是否控制儿茶酚胺分泌。 尽管这项工作检查了肾上腺的调节，但很可能存在类似的机制 控制许多不同类型内分泌组织的激素释放。

项目成果

Fasting induces a form of autonomic synaptic plasticity that prevents hypoglycemia.

禁食会诱导一种自主神经突触可塑性，从而预防低血糖。

• DOI: 10.1073/pnas.1517275113
• 发表时间: 2016
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Wang,Manqi;Wang,Qian;Whim,MatthewD
• 通讯作者: Whim,MatthewD

Pancreatic beta cells synthesize neuropeptide Y and can rapidly release peptide co-transmitters.

• DOI: 10.1371/journal.pone.0019478
• 发表时间: 2011-04-29
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Whim MD