REGULATION OF VASOPRESSIN MRNA

这项研究计划的目标是确定 神经递质、神经肽、离子通量和第二信使系统 视上核神经元血管加压(VP)基因的调控 慢性脱水过程中的细胞核。黄瓜的器官培养外植体 下丘脑-神经垂体系统(HNS)将用于这些 学习。HNS外植体包括位于视上核的VP神经元。 核，其轴突通过正中隆起向尾部延伸，以及 它们的轴突终末位于神经叶。HNS外植体可靠地增加VP 释放到培养上清液中以响应高张力以及 乙酰胆碱、苯肾上腺素、荷包牡丹碱和血管紧张素II。因此，这些 外植体提供了确定细胞外和 调控VPmRNA长度和含量的细胞内信号 这些神经元。这项建议的具体目标是： 1.进一步研究高张状态对VP基因表达的影响 HNS外植体的大小和含量。 2.确定高张状态对VPm RNA大小的影响 SON神经元中的含量反映了渗透压诱导 神经元的去极化或突触介导的激活。 3.评价特定神经递质/神经肽的作用 在诱导VPmRNA含量和大小增加的反应中 为了高张力。 4.评价离子通量在高渗和高渗中的作用 神经递质/神经肽诱导的VP mRNA大小增加 或内容。 5.评价细胞内第二信使系统在细胞周期中的作用 高张引起的VPmRNA大小或含量的增加 神经递质/神经肽。 细胞外利用的细胞内信号的鉴定 调节基因表达的刺激对 理解多肽跨膜调控的分子基础 神经元的合成。这些耦合过程中的异常可能 是一些神经病理情况的基础。因此，建议的 VP合成和释放调控机制的研究进展 可能提供对正常和病理情况的重要洞察 神经系统。

The objective of this research program is to determine the role of neurotransmitters, neuropeptides, ion fluxes, and second messenger systems in the regulation of vasopression (VP) mRNA in neurons of the supraoptic nuclei during chronic dehydration. Organ-cultured explants of the hypothalamo-neurohypophyseal system (HNS) will be utilized in these studies. The HNS explant includes the VP neurons located in the supraoptic nuclei, their axons extending caudally through the median eminence, and their axon terminals in the neural lobe. HNS explants reliably increase VP release into the culture medium in response to hypertonicity as well as acetylcholine, phenylephrine, bicuculline, and angiotensin II. Thus, these explants provide the opportunity to determine the extracellular and intracellular signals which regulate the length and content of VPmRNA in these neurons. The specific aims of this proposal are: 1. To further characterize the effect of hypertonicity on VP mRNA size and content in HNS explants. 2. To determine whether the effect of hypertonicity on VPmRNA size and content in SON neurons reflects osmotically induced depolarization or synaptically mediated activation of the neuron. 3. To evaluate the role of specific neurotransmitters/neuropeptides in inducing the increase in VPmRNA content and size in response to hypertonicity. 4. To evaluate the role ion fluxes in hypertonicity and neurotransmitter/neuropeptide induced increases in VP mRNA size or content. 5. To evaluate the role of intracellular second messenger systems in the increases in VPmRNA size or content induced by hypertonicity and neurotransmitters/neuropeptides. Identification of the intracellular signals utilized by extracellular stimuli to regulate gene expression is of crucial importance to understanding the molecular basis of transmembrane control of peptide synthesis in neurons. Abnormalities in these coupling processes may underlie some neuropathological conditions. Therefore, the proposed approaches to studying the mechanisms regulating VP synthesis and release may provide important insight into normal and pathological conditions in the nervous system.