SOMATOSTATIN-28 CONTROL OF VASOPESSIN & EPINEPHRINE

这项拨款申请中建议的研究的主要目标 是为了确定大脑生长抑素在调节中的作用 垂体加压素和肾上腺肾上腺素的分泌。 生长抑素-28(SS-28)，放置在离散的大脑区域， 升高血浆加压素浓度，降低血浆 肾上腺素水平。SS-28的持续输注 侧脑室产生显著的脑室衰竭 下丘脑室旁核内的加压素水平 免疫细胞化学法测定下丘脑。耗尽 脑组织生长抑素联合半胱胺减轻失血性脑出血 血浆加压素浓度升高。生长抑素- 类肽(SLP)存在于大脑中涉及的区域 在调节垂体加压素和肾上腺肾上腺素中的作用 分泌物。 SS-28刺激作用部位的系统研究 加压素和抑制肾上腺素的分泌以及 这些部位与SLP解剖分布的关系 在中枢神经系统(CNS)内被提出。这些 目标将通过药理学、生理学相结合来实现 神经解剖学方法论。基于我们对神经的了解 调节加压素和肾上腺素的途径 SLP的分泌和中枢神经系统分布的信息 将为SS-28的行动地点选择评估区域。 在确定这些地点之后，将进行分析 神经中SLP的存在及其细胞来源 该区域内的终端。含有特异性SLP的蛋白的作用 加压素分泌的生理调节途径 将使用可用的工具进行评估以修改版本或 内源性SLP的作用。其他研究将评估这一角色 加压素分泌的其他特征假定调节因子 在调节SS-28的作用中 这些研究将增加我们对 特定的脑内含SLP的通路在调节 垂体加压素和肾上腺肾上腺素的分泌。

The primary goal of the studies proposed in this grant application is to determine the role of brain somatostatin in the regulation of pituitary vasopressin and adrenal epinephrine secretion. Somatostatin-28 (SS-28), placed into discrete brain regions, elevates plasma concentration of vasopressin and decreases plasma levels of epinephrine. Continuous infusion of SS-28 into the lateral cerebroventricle produces a significant depletion of vasopressin levels within the paraventricular nucleus of the hypothalamus as determined by immunocytochemistry. Depletion of brain somatostatin with cysteamine attenuates hemorrhage-induced elevation of plasma concentration of vasopressin. Somatostatin- like peptides (SLP) are present in brain regions which are involved in the regulation of pituitary vasopressin and adrenal epinephrine secretion. A systematic search for the sites of action of SS-28 to stimulate vasopressin and to inhibit epinephrine secretion and the relationship of these sites to the anatomic distribution of SLP within the central nervous system (CNS) is proposed. These objectives will be achieved by combining pharmacologic, physiologic and neuroanatomic methodologies. Based on our knowledge of neural pathways that regulate vasopressin and adrenal epinephrine secretion and on information on the CNS distribution of SLP, brain areas will be chosen for evaluation for sites of action of SS-28. Following the identification of these sites, analyses will te made for the presence and cellular origin of SLP contained in nerve terminals within this region. The role of specific SLP-containing pathways in the physiologic regulation of vasopressin secretion will be assessed using available tools to modify the release or action of endogenous SLP. Additional studies will assess the role of other characterized putative regulators of vasopressin secretion in mediating the actions of SS-28 These studies will increase our understanding of the role that specific brain SLP-containing pathways play in the regulation of pituitary vasopressin and adrenal epinephrine secretion.