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

描述(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，释放儿茶酚胺激素，肾上腺素和去甲肾上腺素，进入血液。在战斗或逃跑的反应中，这些荷尔蒙从肾上腺释放出来，为有机体应对可能对循环、呼吸、肌肉骨骼和代谢控制系统施加的突然需求做好准备。与他们广泛的行动一致的是，肾上腺的不适当活动与包括高血压在内的各种疾病有关。这项拟议研究的长期目标是确定正常情况下控制这些肾上腺激素释放的机制。一种控制途径被认为涉及递质的分泌，这些递质与儿茶酚胺共同释放，并在腺体本身内调节“短反馈环”。这些联合传播者的身份和他们获释的条件(S)尚不清楚。然而，一个强有力的候选者是神经肽Y，这是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，它的释放介导了调节儿茶酚胺分泌的短反馈环。为了验证这一假设，我们有三个特定的目标，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。在第一组实验中，我们将检验NPY的净作用是增加儿茶酚胺分泌的假设。我们的第二个具体目标是验证NPY的释放可以以自分泌(细胞受限)的方式调节儿茶酚胺分泌的假设。在第三组实验中，我们将测试NPY也可以通过改变突触前输入的强度来调节儿茶酚胺分泌的假设，突触前输入通常限制儿茶酚胺的分泌。通过体外和原位准备，通过电生理和分子技术，我们将全面确定局部反馈通路是否控制儿茶酚胺的分泌。虽然这项工作研究了肾上腺的调节，但类似的机制可能控制许多不同类型的内分泌组织的激素释放。与公共健康相关：肾上腺的内侧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，这对于开发可以纠正它们不适当或过度释放的治疗方法是必要的。

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.