ENDOGENOUS OPIATES IN THE REGULATION OF VASOPRESSIN

这个项目的目标是阐明阿片肽的作用。 在垂体后叶的生理学和病理生理学中 功能。具体地说，拟议的研究将测试 阿片类中间神经元是中枢神经系统的组成部分 介导血容量影响的传入通路 加压素的分泌。为此，阿片类拮抗剂专用于 将给大鼠注射Mu、Delta或kappa受体，以确定 拮抗剂改变了加压素对渗透压的反应， 血液动力学或糖耐量下降的影响。以确定受体的位置 调节这些作用的拮抗剂也将被注射 通过立体定向进入脑室来确定脑室是否堵塞 这些区域中的阿片受体复制了对 全身性血管加压素的特异性反应 对抗者的管理。相同的阿片类拮抗剂 将被放射性标记并与放射自显影一起使用以确定 体内特定的结合部位。血容量和血氧饱和度的影响 对个人阿片类药物合成和/或分泌的其他刺激 这些区域中的多肽也将使用 放射性标记氨基酸的掺入和放射免疫分析 专门为此目的而开发的。在这些实验中， 组织将通过对离散的大脑区域进行穿孔活组织检查来获得 问题中的多肽将被提取并由 免疫分析以及高效液相和葡聚糖凝胶层析。 最后，为了阐明它们的治疗潜力，这些拮抗剂 将被尖锐地和长期地给予，以确定它们是否正确 血管加压素分泌异常在动物模型中的作用 利尿剂滥用，心脏和肝脏衰竭。这些信息 从这些研究中获得的信息将有助于阐明 内源性阿片类药物在大脑功能中的作用，还可能提供 治疗好S并明确其发病机制的有力新工具 许多临床表现为水盐平衡失调。

The goal of this project is to elucidate the role of opioid peptides in the physiology and pathophysiology of posterior pituitary function. Specifically, the proposed studies will test the hypothesis that opioid interneurons are an integral part of the afferent pathways which mediates the effect of blood volume on vasopressin secretion. To this end, opioid antagonists specific for mu, delta or kappa receptors will be given to rats to determine if the antagonists alter the vasopressin response to osmotic, hemodynamic or glucopenic influences. To locate the receptors that mediate these effects, the antagonists also will be injected stereotaxically into brain ventricles to determine if blockage of opiate receptors in these areas reproduces the inhibition of specific vasopressin responses produced by systemic administration of the antagonists. The same opioid antagonists will be radiolabelled and used with autoradiography to determine specific in vivo binding sites. The effect of blood volume and other stimuli on the synthesis and/or secretion of individual opioid peptides in these regions will also be investigated using incorporation of radiolabelled aminoacids and radioimmunoassays specifically developed for this purpose. In these experiments, tissue will be obtained by punch biopsies of discrete brain areas and the peptides in questions will be extracted and identified by immunoassay as well as HPLC and Sephadex chromatography. Finally, to clarify their therapeutic potential, these antagonists will be given acutely and chronically to determine if they correct abnormalities in vasopressin secretion in animal models of diuretic abuse, cardiac and liver failure. The information obtained from these studies will help to clarify the role of endogenous opioids in brain function and may also provide a powerful new tool to treat s well as to define the pathogenesis of many clinical disorders of salt and water balance.