VASOPRESSIN SIGNALING IN COLLECTING TUBULE CELLS

收集管细胞中的加压素信号传导

• 批准号: 3462524
• 负责人: MARIA BURNATOWSKA-HLEDIN
• 金额: $ 10.31万
• 依托单位: HOPE COLLEGE
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-09-01 至 1994-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3462524
• 关键词: adenylate cyclase; binding proteins; biological fluid transport; biological signal transduction; calcium; cyclic AMP; guanine nucleotides; homeostasis; hormone metabolism; hormone receptor; hormone regulation /control mechanism; laboratory rabbit; membrane permeability; molecular biology; monoclonal antibody; oxygen consumption; phospholipase C; renal tubular transport; renal tubule; second messengers; sodium channel; solute; vasopressins

The long term objective of this proposal is to determine the cellular signal transduction mechanism(s) by which vasopressin, a hormone essential to the regulation of body fluid homeostasis, exerts control over the terminal nephron. ln addition to the considerable evidence supporting the role for cyclic AMP as a second messenger, cytosolic free calcium has also been proposed to regulate the hormonal responses, either independently or synergistically with cAMP. The hypothesis to be tested by the proposed studies is that vasopressin affects cellular function in the collecting tubule through two distinct receptor-effector systems localized on the same cell, and that the regulation of vasopressin signal occurs by the activation and perhaps interaction of the two systems. Understanding the molecular mechanism by which vasopressin regulates nephron function is impaired by the limited amount, heterogeneity, and relatively inaccessibility of the cells which it regulates. The use of monoclonal antibodies as immunoaffinity reagents for the isolation of large quantities of homogenous cell populations has recently made it possible to isolate segment- specific renal cells. This approach will be used to isolate collecting tubule-specific cells to determine: 1) what is the cellular mechanism of vasopressin action 2) are both vasopressin receptors (Vl and V2) present on the same cell 3) is this dual signal transduction system acting independently or synergistically, and 4) is the sodium uptake and oxygen consumption in these cells regulated by this dual signal-transduction system. These studies will provide information on the molecular mechanism by which vasopressin regulates water and solute transport in the distal segment. In addition, it will further our understanding of a dual signal-transduction systems in general.

该提议的长期目标是确定 血管加压素A，A的细胞信号转导机制 激素对体液稳态的调节必不可少的 对末端肾单位施加控制。 LN增加了支持该角色的大量证据 循环AMP作为第二使者，胞质免费钙也具有 提议调节激素反应，要么 独立或与营地协同。 拟议的研究要检验的假设是 加压素影响收集小管中的细胞功能 通过两个不同的受体效应系统 同一细胞，并且加压素信号的调节是由 两个系统的激活和相互作用。 了解加压素的分子机制 调节肾单位功能受到有限的损害， 细胞的异质性和相对无法访问 它调节。 单克隆抗体用作免疫亲和力 分离大量同质细胞的试剂 种群最近使分离细分市场成为可能 特定的肾细胞。 这种方法将用于隔离 收集小管特异性细胞以确定：1） 加压素作用的细胞机制2）都是加压素 同一细胞上存在的受体（VL和V2）3） 信号转导系统独立或协同作用， 4）是这些细胞中的钠摄取和氧气消耗 受此双重信号转导系统的调节。 这些研究将提供有关分子机制的信息 加压素调节水和溶质转运 远端段。 此外，这将进一步我们对 通常，双重信号转导系统。