RECEPTOR MECHANISMS IN HEPATOCYTES

肝细胞中的受体机制

• 批准号: 3231178
• 负责人: PETER G BRADFORD
• 金额: $ 8.4万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-04-01 至 1988-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3231178
• 关键词: autoradiography; calcium metabolism; cell membrane; cyclic AMP; hormone regulation /control mechanism; inositol phosphates; ion transport; liver cells; liver pharmacology; membrane potentials; radionuclides

The general goal of this project is to understand better the mechanisms by which hormone receptors regulate ion fluxes in the liver. Emphasis will be placed on cellular mechanisms making use of ion transport measurements and intracellular Ca++ indicators. The significance of this research is twofold: First, understanding these receptor mechanisms in the liver is relevant to the pathophysiology of diabetes since these same receptors regulate the release of glucose into the blood from the liver. Second, similar receptor-ion interactions are involved in a wide variety of health related functions, including vascular reactivity and CNS functions. The initial studies in this project will focus on a quantitative evaluation of hormone induced efflux of K+ which is believed to be mediated by an elevation of intracellular ionized Ca++. Changes in K+ flux will be determined by use of 86Rb flux and a cellular perifusion system. Changes in cytosolic Ca++ will be detecterd by quin-2 fluorescence. The number and regulation of K+ channels will be probed by 125I-apamin binding. An hypothesis as to a specific mechanism for hormone induced intracellular Ca release will be investigated. Specifically, the role of soluble inositol phosphates, as second messengers or cellular Ca modulators will be examined.

本项目的总体目标是通过以下方式更好地了解这些机制： 哪些激素受体调节肝脏中的离子流。 重点将 放置在利用离子传输测量的细胞机制上， 细胞内Ca++指标。 本研究的意义在于 两方面：首先，了解肝脏中的这些受体机制， 与糖尿病的病理生理学相关，因为这些相同的受体 调节葡萄糖从肝脏释放到血液中。 第二、 类似的受体-离子相互作用涉及多种健康 相关功能，包括血管反应性和CNS功能。 的 本项目的初步研究将侧重于对以下方面进行定量评价： 激素诱导的K+外排被认为是由 细胞内游离Ca++升高。 K+通量的变化将是 通过使用86 Rb通量和细胞灌注系统测定。 变化 用quin-2荧光检测胞浆Ca ~（++）。 数量和 K+通道的调节将通过125 I-蜂毒肽结合来探测。 一个 激素诱导细胞内Ca ~（2+）特异机制假说 释放将被调查。 具体来说，可溶性肌醇 磷酸盐，作为第二信使或细胞钙调节剂将被检查。