DEPRESSION: ATPASE REGULATOR AND NOREPINEPHRINE

抑郁症：ATP酶调节剂和去甲肾上腺素

基本信息

批准号：
3376067
负责人：
Alan C Swann
金额：
$ 12.25万
依托单位：
UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-09-01 至 1989-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3376067
关键词：
adenosinetriphosphatase antidepressants autoradiography brain cell cardiac glycosides catecholamines cyclic AMP depression gel electrophoresis human tissue ion transport membrane permeability neurotransmitter metabolism norepinephrine thyroid hormones

项目摘要

The research in this proposal will examine the regulation of (Na+,K+)-ATPase in vivo by norepinephrine and by a specific endogenous inhibitor of the enzyme. (Na+,K+)-ATPase is the enzymatic basis of energy-dependent Na+ and K+ transport and has a central role in the regulation of intracellular cation concentrations and, hence, of membrane potential, cell excitability, and energy utilization. The experiments in this proposal are in four parts. 1) Experiments examining regulation of (Na+,K+)-ATPase, and interactions between norepinephrine and thyroid or adrenocortical hormones in regulation of (Na+,K+)-ATPase, and interactions between noradrenergic regulation of (Na+,K+)-ATPase and other mechanisms of Na+ Ca++ transport. 2) Experiments on specificity of transmitter regulation of (Na+,K+)-ATPase will examine specificity with respect to a) transmitter, receptor subtype, and tissue, b) molecular form of enzyme, using polyacrylamide gel electrophoresis to separate the two forms of enzyme, and c) localization of enzyme regulated by norepinephrine, using radioautography. The latter experiments will provide pilot data for development of studies using positron emission tomography. 3) Experiments on the mechanism of the noradrenergic effects will examine (Na+,K+)-ATPase-mediated transport in vitro. Initial experiments will compare effects in synaptosomes, dissociated brain cells, and brain slices. Further experiments will examine transmitter specificity, effects of prior exposure to norepinephrine, hormone status, or treatment with psychoactive drugs in vivo, effects of electrical stimulation in vitro, and roles of cation fluxes and of cyclic nucleotides. 4) Experiments in man will use stimulation of cation shifts by endogenous catecholamines to develop a means for examining noradrenergic regulation of (Na+,K+)-ATPase in intact man. These studies will provide the basis for studies of noradrenergic regulation of (Na+,K+)-ATPase in normal man and in conditions related to functions of the norepinephrine-(Na+,K+)-ATPase system, including affective disorders, eating disorders, and disorders of neural arousal.

该提案中的研究将研究（Na+，k+） - 用去甲肾上腺素和特定的内源性体内ATPase在体内酶的抑制剂。（Na+，K+） - ATPase是酶促的依赖能量的Na+和K+传输，并且在调节细胞内阳离子浓度，因此膜的调节潜力，细胞兴奋性和能量利用。实验该建议分为四个部分。 1）检查调节的实验（Na+，K+） - ATPase，以及去甲肾上腺素与甲状腺或甲状腺之间的相互作用或（Na+，K+）ATPase和相互作用的调节中的肾上腺皮质激素在（Na+，K+） - ATPase和其他机制之间的去肾上腺素能调节之间 NA+ CA ++运输。 2）关于发射器特异性的实验（Na+，K+）的调节 - ATPase将检查有关A的特异性发射器，受体亚型和组织，b）酶的分子形式，使用聚丙烯酰胺凝胶电泳分开两种形式酶和c）使用去甲肾上腺素调节的酶定位，使用放射学。后一个实验将为使用正电子发射断层扫描的研究开发。 3）实验关于去甲肾上腺素作用的机制将检查（Na+，K+） - ATPase介导的体外转运。最初的实验将比较突触体，解离的脑细胞和脑的影响切片。进一步的实验将检查发射器特异性，效果先前暴露于去甲肾上腺素，激素状态或治疗体内的精神活性药物，体外电刺激的影响，阳离子通量和环状核苷酸的作用。 4）人类实验将使用内源性儿茶酚胺刺激阳离子的转移开发一种检查（Na+，K+）ATPase的去甲肾上腺素能调节的手段完整的人。这些研究将为研究提供基础（Na+，K+） - 正常人和条件下的ATPase（Na+，K+）的去甲肾上腺素能调节与去甲肾上腺素（Na+，K+） - ATPase系统的功能有关，包括情感障碍，饮食失调和神经疾病唤醒。