REGULATION OF VASOPRESSIN MRNA

这项研究计划的目的是确定 神经递质、神经肽、离子流和第二信使系统 调节视上核神经元血管加压素（VP）mRNA 慢性脱水时的细胞核 器官培养的外植体 下丘脑-神经垂体系统（HNS）将用于这些 问题研究 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侧延伸， 神经叶中的轴突末梢 HNS外植体可靠地增加VP 响应高渗而释放到培养基中，以及 乙酰胆碱、苯乙哌啶、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 细胞内信号调节VPmRNA的长度和含量， 这些神经元。 这项建议的具体目标是： 1. 进一步表征高渗对VP mRNA的影响 HNS外植体的大小和含量。 2. 为了确定高渗是否对VPmRNA大小的影响， SON神经元中的含量反映了 去极化或突触介导的神经元激活。 3. 评价特定神经递质/神经肽的作用 诱导VPmRNA含量和大小的增加， 到高渗。 4. 为了评估离子通量在高渗性中的作用， 神经递质/神经肽诱导VP mRNA大小增加 或内容 5. 为了评价细胞内第二信使系统在细胞凋亡中的作用， 高渗引起的VPmRNA大小或含量增加， 神经递质/神经肽。 识别细胞外信号所利用的细胞内信号 调节基因表达的刺激物对于 了解肽跨膜调控的分子基础 神经元的合成 在这些耦合过程中， 是一些神经病理学病症的基础 因此，建议 VP合成和释放调控机制的研究进展 可以提供重要的洞察正常和病理条件， 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.