CELLULAR REGULATION OF PHOSPHATE TRANSPORT IN KIDNEY

肾脏磷酸盐转运的细胞调节

基本信息

批准号：
3152123
负责人：
THOMAS P DOUSA
金额：
$ 14.31万
依托单位：
MAYO CLINIC ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
1982
资助国家：
美国
起止时间：
1982-04-01 至 1986-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3152123
关键词：
alkaline phosphatase brush border membrane calcium metabolism cyclic AMP dietary trace element glucocorticoids gluconeogenesis kidney metabolism malnutrition membrane permeability nicotinamide adenine dinucleotide parathyroid hormones phosphates phosphorus metabolism disorders renal cortex renal tubular transport

项目摘要

The goal of this project is to elucidate cellular mechanisms by which phosphate (Pi) reabsorption in proximal tubules is regulated at luminal brush border membrane (BBM). The investigations are based on the hypothesis which proposes that regulation of Na+-dependent BBM transport of Pi involves nicotinamide adenine dinucleotide (NAD) and gluconeogenesis (GNG), as major regulatory components. Specifically, we will determine: 1. How the rate of GNG, possibly via the NAD system, modulates GGM uptake of Pi. 2. The mechanism by which NAD interacts with BBM and how this interaction relates to the inhibitory effect of NAD on BBM transport of Pi. 3. How parathyroid hormone (PTH), via cyclic AMP, protein kinase, and Ca++ fluxes stimulates GNG, increses NAD+ generation and thereby inhibits the BBM transport of Pi. 4. Whether gluccorcorticoid administration decreases and dietary Pi deprivation increases BBM uptake of Pi via the effect of GNG and on NAD+ levels. 5. Determine the biochemical mechanism by which nicotinamide administration causes inhibition of BBM uptake of Pi and phosphaturia. 6. To localize the above specified components and regulatory sequences in specific subsegments of proximal tubules, in intracellular compartments of tubular cells, and to determine the differences between superficial and juxtamedullary cortical proximal tubules. These studies, conducted with a combination of biochemical, cellular and microdissection techniques, will elucidate the fundamental principles of regulatio of Pi reabsorption in proximal tubules. The results will also provide a new basis for understanding the pathogenesis of disorders of renal tubular Pi transport and thus will help to establish rationale for new diagnostic and therapeutic procedures in these disorders.

该项目的目的是阐明细胞机制近端小管中的磷酸盐（PI）重吸收在腔内调节刷边界膜（BBM）。调查是基于假设提出了依赖Na+依赖性BBM转运的调节 PI涉及烟酰胺腺嘌呤二核苷酸（NAD）和糖异生（gng），作为主要的监管组件。具体来说，我们将确定： 1。GNG的速率可能通过NAD系统调节GGM的吸收 pi。 2。NAD与BBM相互作用的机制以及如何相互作用与NAD对BBM转运的抑制作用有关 pi。 3。甲状旁腺激素（PTH）如何通过环状AMP，蛋白激酶和 Ca ++通量会刺激GNG，增加NAD+的生成，从而抑制 PI的BBM运输。 4。glucorcorcorioid是否给药减少和饮食PI剥夺增加了BBM通过PI的吸收 GNG和NAD+水平的影响。 5。确定生化机制烟酰胺给药会引起BBM摄取PI的抑制和磷酸。 6。本地将上述组件和近端小管的特定子侦察中的调节序列，在管状细胞的细胞内室，并确定浅表和近叶皮质近端之间的差异小管。这些研究结合了生化，细胞和显微解剖技术将阐明基本 PI近端小管中PI重吸收的原理。这结果还将为理解的发病机理提供新的基础肾小管PI运输的疾病，因此将有助于建立这些新诊断和治疗程序的基本原理疾病。