COTRANSMITTER CONTROL OF ADRENAL MEDULLARY FUNCTION

肾上腺髓质功能的协同递质控制

• 批准号: 2215529
• 负责人: ARUN R. WAKADE
• 金额: $ 16.76万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 1997-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2215529
• 关键词: acetylcholine; adenylate cyclase; adrenal medulla; catecholamines; cell population study; choline acetyltransferase; cholinergic receptors; chromaffin cells; denervation; enzyme activity; epinephrine; immunocytochemistry; in situ hybridization; laboratory rat; nerve endings; neurons; neuropeptides; neurotransmitter receptor; neurotransmitters; norepinephrine; perfusion; pituitary gland; preganglionic fiber; secretion; vasoactive intestinal peptide

The adrenal gland plays a crucial role in maintaining homeostasis during stressful situations by releasing cortical and medullary hormones into the blood stream. For over 10 years we have been particularly interested in the control of adrenal medulla by its preganglionic sympathetic neurons. These splanchnic neurons are cholinergic in nature and acetylcholine (ACh) released from the their terminals is the known stimulus of catecholamine secretion from chromaffin cells. In 1987 our analysis hinted that other substances, in addition to ACh could be released from nerve endings to stimulate the chromaffin cells. We used a series of physiological, pharmacological and immunohistochemical techniques together with radioimmunoassay to identify the nature of the non-cholinergic transmitter as vasoactive intestinal polypeptide (VIP). The new concept of non- cholinergic participation in the adrenal medulla has received wide acceptance because VIP, but not ACh, proved to be the stimulus for elevation of cAMP and consequent events in chromaffin cells. Within the last few years a new polypeptide, pituitary adenylate cyclase; activating polypeptide (PACAP), was identified as a member of the VIP-secretin family. PACAP has many similarities with VIP and has been found in neural tissues. These developments have opened new areas of research to further understand the physiological significance of multiple transmitter control of adrenal medullary secretion. In the present proposal we are raising three important questions. First, because of two lingering concerns regarding the role of VIP as a sole non-cholinergic transmitter, we question whether PACAP could be the other non-cholinergic transmitter. Second, our demonstration that ACh and VIP are released by different frequencies of splanchnic nerve stimulation raises the question of whether cholinergic and peptidergic transmitters are located in the same or different nerve endings. Third, because it is well known that there are two populations of chromaffin cells, epinephrine and norepinephrine rich, which lead to different proportions of the two catecholamines under different stressor conditions, we question whether ACh and peptides preferentially secrete epinephrine or norepinephrine. These issues will be addressed using techniques of immunohistochemistry, molecular biology, biochemistry and physiology with the combined expertise of our own laboratory and that of our most able colleagues.

肾上腺在维持体内平衡方面发挥着至关重要的作用 通过将皮质和髓质激素释放到大脑中来缓解压力情况 血流。 十多年来，我们一直特别感兴趣 肾上腺髓质由节前交感神经元控制。 这些内脏神经元本质上是胆碱能神经元，并且具有乙酰胆碱 (ACh) 从其末端释放的是已知的儿茶酚胺刺激物 嗜铬细胞分泌。 1987 年，我们的分析暗示其他 除乙酰胆碱外，其他物质也可从神经末梢释放 刺激嗜铬细胞。我们使用了一系列的生理、 药理学和免疫组织化学技术以及 放射免疫测定法鉴定非胆碱能递质的性质 作为血管活性肠多肽（VIP）。新概念非 胆碱能参与肾上腺髓质已被广泛 接受是因为 VIP 而不是 ACh 被证明是刺激 cAMP 升高以及嗜铬细胞中的后续事件。 内 近几年出现了一种新的多肽，垂体腺苷酸环化酶；激活 多肽（PACAP），被鉴定为VIP-分泌素的成员 家庭。 PACAP 与 VIP 有许多相似之处，并且已在神经网络中被发现 组织。这些发展开辟了新的研究领域，以进一步 了解多个发射器控制的生理意义 肾上腺髓质的分泌。在本提案中，我们提出 三个重要问题。首先，由于两个挥之不去的担忧 关于 VIP 作为唯一的非胆碱能递质的作用，我们 质疑 PACAP 是否可能是另一种非胆碱能递质。 其次，我们演示了ACh和VIP是由不同的释放者 内脏神经刺激的频率提出了一个问题： 胆碱能递质和肽能递质位于同一或 不同的神经末梢。第三，因为众所周知，有 两个嗜铬细胞群，富含肾上腺素和去甲肾上腺素， 导致两种儿茶酚胺的比例不同 不同的应激条件下，我们质疑乙酰胆碱和肽是否 优先分泌肾上腺素或去甲肾上腺素。这些问题将会 使用免疫组织化学、分子生物学技术来解决， 生物化学和生理学以及我们自己的综合专业知识 实验室和我们最有能力的同事的实验室。