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

基本信息

批准号：
7992614
负责人：
MATTHEW WHIM
金额：
$ 2.85万
依托单位：
LSU HEALTH SCIENCES CENTER
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-04-09 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7992614
关键词：
Address Adrenal Glands Adrenal Medulla Adrenal hormone preparation Affect Blood Blood Glucose Blood Pressure Calcium Catecholamines Cells Chromaffin Cells Cytoplasmic Granules Diabetes Mellitus Disease Disputes Endocrine Epinephrine Feedback Gated Ion Channel Gland Heart Rate Hormones Immune system In Situ In Vitro Knock-out Knockout Mice Mediating Metabolic Control Metabolism Molecular Mus Musculoskeletal Nature Neurons Neurotransmitters Norepinephrine Organ Organism Pathway interactions Pattern Peptides Physiological Preparation Process RNA Interference Receptor Activation Regulation Role Slice Spinal Spinal Cord Surface Synapses Synaptic Receptors System Techniques Testing Tissues Work adrenal hypertension autocrine carbon fiber controlled release excitatory neuron fighting hormone control mechanism meetings neuropeptide Y polypeptide receptor relating to nervous system research study respiratory response therapy development voltage voltage clamp

项目摘要

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. These include hypertension (adrenal over-activity) and diabetes (adrenal under-responsiveness). 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 a "short feedback loop" within the gland itself. The identity 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 a short feedback loop that regulates 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 idea that the net effect of NPY is to increase the secretion of the catecholamines. Our second specific aim is to determine whether the release of NPY can regulate catecholamine release 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 test the hypothesis that a local feedback pathway controls 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. Project Narrative The inner region of the adrenal gland secretes hormones that regulate blood pressure and metabolism. 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。在战斗或逃跑反应期间，这些激素从肾上腺释放，并为生物体做好准备，应对循环、呼吸、肌肉骨骼和代谢控制系统可能出现的突然需求。与其广泛的作用相一致，肾上腺的不适当活动与多种疾病有关。这些包括高血压（肾上腺过度活动）和糖尿病（肾上腺反应不足）。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，一种控制途径是由与儿茶酚胺共同释放的递质的分泌产生的，并介导腺体本身内的“短反馈回路”。这些共同发射者的身份以及它们释放的条件尚不清楚。然而，一个强有力的候选者是神经肽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。为了检验这一假设，我们有 3 个具体目标，我们将使用小鼠交感神经元（嗜铬细胞）和肾上腺切片来解决这些问题。在第一组实验中，我们将测试 NPY 的净效应是增加儿茶酚胺的分泌这一想法。我们的第二个具体目标是确定 NPY 的释放是否可以以自分泌（细胞限制）方式调节儿茶酚胺的释放。在第三组实验中，我们将检验以下假设：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学和分子技术，我们将全面检验局部反馈途径控制儿茶酚胺分泌的假设。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释放激素。项目叙述肾上腺的内部区域分泌调节血液的激素压力和新陈代谢。了解这些分子的释放方式需要控制来开发可以纠正其症状的治疗方法释放不当或过度。