DEPRESSION, CATION TRANSPORT, AND ENERGY METABOLISM

抑郁、阳离子传输和能量代谢

• 批准号: 3069770
• 负责人: Alan C Swann
• 金额: $ 5.77万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-01-01 至 1987-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3069770
• 关键词: active transport; adenosinetriphosphatase; alcoholism /alcohol abuse; bioenergetics; cyclic AMP; electrical potential; human subject; human tissue; ion transport; neural transmission; neurons; norepinephrine; psychophysiology

This ADAMHA Research Scientist Development Award, Type II, is sought in order to carry out research examining the relationship between energy metabolism and nerve activity and its regulation in affective disorders and alcoholism. The experimental model used will be (NA+, K+)-ATPase, the enzymatic mechanism of active cation transport and of stimulation-dependent energy metabolism in nerve, and its regulation by norepinephrine. The research will be based on my previous data describing the reaction mechanism of (Na+, K+)-ATPase, the possible presence of a nerve-specific form of enzyme, and the regulation of nerve-specific enzyme by noradrenergic innervation. Experiments on enzyme regulation and nerve activity in vivo will examine a) regulation by norepinephrine in terms of localization of regulated enzyme, specificity for nerve enzyme and for norepinephrine, and role in noradrnergic effects, b) methods of measuring nerve-specific enzyme, c) characterization of a possible endogenous sodium pump inhibitor and its interactions with norepinephrine, and d) physiology of the norepinephrine-ATPase system including peripheral-central interactions and role in energy balance. Experiments on regulation in vitro will examine the relationship between the energy of cation binding and cation transport and the effects on this of norepinephrine and electrical stimulation, and the relationship between (Na+, K+)-ATPase activity and energy production. Approaches to the study of this system in nerve cells will be developed using isolated cells from liver and from brown adipose tissue. The hypothesis being tested will be that nerve-specific enzyme is regulated by norepinephrine via cylic AMP. In clinical studies, red and white blood cell (Na+, K+)-ATPase and plasma levels of the inhibitor will be compared in normal, alcoholic, and depressed patients. Nerve-specific enzyme and norepinephrine stimulation will be compared using enzyme from postmortem brain samples from these groups. In the course of these studies, I will develop methods for measuring energy metabolism in isolated cells, measurement of ion transport in artificial vesicles, and measurement of membrane potentials in vitro.

该ADAMHA研究科学家发展奖（II型）被寻求 为了进行研究，研究能源之间的关系 代谢和神经活动及其在情感障碍中的调节 酗酒。 所使用的实验模型将为（Na+，K+） - ATPase， 活性阳离子转运和刺激依赖性的酶促机制 神经中的能量代谢及其对去甲肾上腺素的调节。 这 研究将基于我以前描述反应的数据 （Na+，K+）的机制 - ATPase，可能存在神经特异性的 酶的形式，以及通过调节神经特异性酶 去肾上腺素能神经。 酶调节和神经的实验 体内的活动将检查a）用去甲肾上腺素调节 调节酶的定位，神经酶的特异性和 去甲肾上腺素和在Noradrnergic效应中的作用，b）测量方法 神经特异性酶，c）可能内源钠的表征 泵抑制剂及其与去甲肾上腺素的相互作用，d）生理 用于外围中心的去甲肾上腺素-ATPase系统 相互作用和能量平衡中的作用。 关于调节的实验 体外将检查阳离子结合能量之间的关系 和阳离子的运输以及对去甲肾上腺素和这种影响的影响 电刺激以及（Na+，K+）ATPase之间的关系 活动和能源生产。 研究该系统的方法 神经细胞将使用肝脏的分离细胞以及 棕色脂肪组织。 检验的假设是 神经特异性酶通过囊肿AMP受到去甲肾上腺素的调节。 在 临床研究，红色和白色血细胞（Na+，K+） - ATPase和等离子体 将在正常，酒精和 沮丧的患者。 神经特异性酶和去甲肾上腺素刺激 将使用来自这些杀后脑样本的酶进行比较 组。 在这些研究过程中，我将开发用于 测量孤立细胞中的能量代谢，测量离子转运 在人造囊泡中，并在体外测量膜电位。