HORMONAL AND IONIC CONTROL OF METABOLISM

新陈代谢的激素和离子控制

• 批准号: 3483313
• 负责人: HOWARD RASMUSSEN
• 金额: $ 25.92万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-06-01 至 1992-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3483313
• 关键词: Gastropoda; adrenal glands; adrenocorticotropic hormone; angiotensin II; biological information processing; brush border membrane; calcium metabolism; calcium transporting ATPase; calmodulin; cholera toxin; cow; cyclic AMP; cytoplasm; drug receptors; electron microscopy; erythrocyte membrane; gastrointestinal absorption /transport; gel filtration chromatography; glucose transport; hormone regulation /control mechanism; human tissue; intestinal mucosa; ion transport; ionophores; laboratory rabbit; laboratory rat; liver cells; mitochondria; muscle contraction; myosins; peptide hormone; phenothiazines; radiotracer

The major aims of the proposed research is to more fully define the mechanisms by which CA2+ regulates cell function during such processes as the hormonal and ionic regulations of aldosterone secretion, from adrenal glomerulosa cells. Cell proliferation of cultured 3T3 cells, and leukocytes function. Specific aims include an elucidation of the temporal patterns of protein phosphorylation, inositol lipid metabolism, Ca2+ metabolism, and protein kinase C function during angiotensin II and bombesin-mediated response in, respectively, glomerulosa and 3T3 cells. The role of type II CaM-dependent protein kinase in the initial phase of cellular response; the immunocytochemical localization of the C-kinase and the possible role of M-kinase in sustained cellular response; the mechanism by which information is conveyed from cell surface to cell interior via the C-kinase branch of the Ca2+ messenger system during the sustained phase of cellular response focusing particularly on changes in Na+/H+ exchange and possible protein kinase cascades; the molecular basis of memory in the C-kinase-mediated phase of cellular response; and a reexamination of the temporal pattern of events in the cAMP messenger system during ACTH-mediate aldosterone secretion from adrenal glomerulosa cells as the system in which to explore these issues. Methods will include studies of Ca2+ fluxes and measurements of intracellular free Ca2+ using both fura 2 and aequorin as indicators; studies of the turnover of inositol lipids and inositols phosphates by both chemical and radio- isotope methods; 2-D gel electrophoresis of the phosphoproteins obtained from extracts of cells; and both light and EM immunocytochemical localization of C-kinase. The problem under investigation is of broad biological interest, and has implications for a wide range of biological phenomena. A better understanding of Ca2+ messenger system function is likely to alter our views of cell growth and proliferation, peptide and steroid hormone secretion, and smooth muscle contraction.

拟议研究的主要目的是更全面地定义 Ca2+调节细胞功能的机制 诸如荷尔蒙和离子法规的过程 醛固酮分泌，来自肾上腺肾小球细胞。 细胞 培养的3T3细胞的增殖和白细胞功能。 具体目的包括阐明的时间模式 蛋白质磷酸化，肌醇脂质代谢，Ca2+ 血管紧张素II期间代谢和蛋白激酶C功能 和bombesin介导的反应分别是肾小球和 3T3细胞。 II型CAM依赖性蛋白激酶在 细胞反应的初始阶段；免疫细胞化学 C-激酶的定位以及M-激酶在 持续的细胞反应；信息的机制 通过C-激酶从细胞表面转移到细胞内部 持续阶段的Ca2+ Messenger系统的分支 细胞反应的重点是NA+/H+的变化 交换和可能的蛋白激酶级联反应；分子 在C-激酶介导的细胞阶段中记忆的基础 回复;并重新审查事件的时间模式 在ACTH米德醛酮期间的营地信使系统中 肾上腺肾小球细胞的分泌 探索这些问题。 方法将包括CA2+的研究 使用两者都使用细胞内游离Ca2+的通量和测量 Fura 2和Aequorin作为指标；研究的研究 化学和放射性的肌醇脂质和肌醇磷酸盐 同位素方法；磷蛋白的二维凝胶电泳 从细胞提取物获得；以及光和em C-激酶的免疫细胞化学定位。 下面的问题 调查具有广泛的生物学兴趣，并且具有含义 对于广泛的生物学现象。 更好的理解 CA2+ Messenger系统功能可能会改变我们对 细胞生长和增殖，肽和类固醇激素 分泌和平滑肌肉收缩。