URINARY CONCENTRATING DEFECTS IN POLYDIPSIA AND HYPOTHYROIDISM

烦渴和甲状腺功能减退症中的尿液浓缩缺陷

基本信息

批准号：
7467365
负责人：
ROBERT W SCHRIER
金额：
$ 35.76万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-08-01 至 2009-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7467365
关键词：
2&apos ,3&apos -Dideoxyadenosine Acute Address Adenylate Cyclase Adrenal Glands Affect Affinity Area Argipressin Binding Body Fluids Brattleboro Rats Cardiac Output Central Diabetes Insipidus Centrifugation Chronic Cirrhosis Clinical Condition Control Animal Cyclic AMP Cyclic AMP-Dependent Protein Kinases Defect Disease Distal Down-Regulation Duct (organ) structure Equilibrium Evaluation Excretory function Experimental Models Experimental Water Deprivation Failure Foundations Funding GTP-Binding Protein alpha Subunits, Gs Generations Glucocorticoids Guanosine Triphosphate Phosphohydrolases Health Heart failure Hour Hypercalcemia Hypothyroidism Immunohistochemistry Intake Intervention Investigation Ions Kidney Knowledge Liquid substance Measurement Mediating Membrane Protein Traffic Mineralocorticoids Molecular Names Nephrons Osmolalities Patients Phosphodiesterase Inhibitors Phosphorylation Plasma Polydipsia Pregnancy Pressoreceptors Principal Investigator Production Program Research Project Grants Proteins Rate Rattus Receptor Activation Regulation Relative (related person)Renal function Research Design Research Personnel Resistance Role Secondary to Signal Transduction Sodium Chloride System Techniques Thyroid Hormones Time Translational Research Urine V2 Receptors Vasoconstrictor Agents Vasopressins Water Water consumption Western Blotting apical membrane aquaporin 3 aquaporin-2 base countercurrent chromatography day deprivation driving force glomerular filtration hemodynamics osmotic minipump phosphoric diester hydrolase prevent programs protein expression receptor receptor binding receptor expression response solute technique development trafficking translational study urea transporter urinary water channel

项目摘要

It has been known for several years that conditions such as chronic primary polydipsia, hypothyroidism, and adrenal disease are associated with abnormalities in urinary concentration and dilution. With the relatively recent discovery of aquaporin water channels and the development of techniques to assess the regulation and function of aquaporins and ion and urea transporters in the kidney, it is now possible to better understand the molecular mechanisms responsible for abnormal urinary concentration and dilution in these conditions. Therefore, the present studies are designed to first correlate alterations in the renal abundance of aquaporin water channels and ion and urea transporters with impaired urinary concentration and dilution in the above-named conditions. This will be accomplished using western immunoblotting techniques. Further investigation into the contributions of altered aquaporin-2 regulation and function to impaired urinary concentration and dilution in these conditions will be performed via a detailed assessment of vasopressin V2 receptor binding and affinity, western immunoblot of inner medulla Gs-alpha and adenylate cyclase abundance, measurement of cAMP production, and evaluation of AQP2 phosphorylation and trafficking. The results of these studies should give us a comprehensive understanding of the mechanisms that contribute to altered urinary concentration and dilution in chronic primary polydipsia, hypothyroidism, and adrenal disease. These results will provide a basis for translational studies addressing these concerns in patients affected by these disorders.

几年来一直知道诸如慢性原发性多次的条件，甲状腺功能减退症和肾上腺疾病与尿浓度和稀释性异常有关。随着水库水通道的相对较新的发现以及肾脏中水通道蛋白，离子和尿素转运蛋白的调控和功能的技术的发展，现在可以更好地了解这些导致异常尿液浓度和稀释的分子机制状况。因此，本研究旨在首先将水通道水通道和离子和尿素转运蛋白的肾脏丰度变化，并在上述条件下尿液浓度和稀释率受损。这将使用西方免疫印迹技术来完成。在这些条件下，对尿浓度和稀释损害的贡献的贡献的进一步研究将通过对加压素V2受体结合和亲和力的详细评估（内部的髓质GS-ALPHA和腺苷酸环化酶循环量的内部免疫印迹）进行详细评估，进行。 cAMP生产的测量以及AQP2磷酸化和贩运的评估。这些研究的结果应使我们对慢性原发性多毒性，甲状腺功能减退症和肾上腺疾病的尿液浓度和稀释的改变的机制有全面的了解。这些结果将为解决受这些疾病影响的患者解决这些问题的转化研究提供基础。