ENDOGENOUS OPIATES IN THE REGULATION OF VASOPRESSIN

这个项目的目标是阐明阿片肽的作用 垂体后叶的生理和病理生理学 功能 具体来说，拟议的研究将测试 假设阿片样物质中间神经元是一个组成部分， 传入通路介导血容量对 加压素分泌 为此，特异性阿片拮抗剂， 将μ、δ或κ受体给予大鼠，以确定 拮抗剂改变加压素对渗透压的反应， 血液动力学或葡萄糖减少影响。 为了定位受体 介导这些效应的拮抗剂也将被注射到 立体定位进入脑室，以确定是否阻塞 这些区域的阿片受体复制了对 系统性血管紧张素转换酶产生的特异性血管加压素反应 拮抗剂的施用。 相同的阿片类拮抗剂 将进行放射性标记，并与放射自显影术一起使用，以确定 特异性体内结合位点。 血容量的影响， 对个体阿片样物质合成和/或分泌的其他刺激 这些区域中的肽也将使用 放射性标记氨基酸的掺入和放射免疫测定 专门为此开发的。 在这些实验中， 将通过对离散的脑区域进行穿刺活组织检查来获得组织 所涉及的肽将被提取和鉴定， 免疫测定以及HPLC和Sephadex色谱法。 最后，为了阐明其治疗潜力，这些拮抗剂 将被给予急性和慢性，以确定他们是否正确， 血管加压素分泌异常的动物模型 滥用利尿剂，心脏和肝脏衰竭 的信息 从这些研究中获得的信息将有助于澄清 内源性阿片类物质在脑功能中的作用，也可能提供 一个强大的新工具，以治疗s和定义的发病机制， 盐和水平衡的许多临床紊乱。

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.