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VASOPRESSIN EFFECT IN DISORDERS OF RENAL CONCENTRATION

血管加压素对肾浓缩障碍的影响

基本信息

批准号：
3151587
负责人：
ROBERT J ANDERSON
金额：
$ 7.86万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
1979
资助国家：
美国
起止时间：
1979-07-01 至 1987-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3151587
关键词：
adenylate cyclase cyclic AMP homeostasis hormone regulation /control mechanism ion transport ischemia kidney metabolism kidney pharmacology lithium magnesium manganese membrane permeability osmosis phosphodiesterases prostaglandin E renal medulla renal tubular transport vasopressins

项目摘要

The effect of the hormone vasopressin (VP) to increase renal collecting tubular water permeability is critical in the maintenance of body water homeostasis. The hydroosmotic effect of VP is dependent upon intracellular generation of 3 feet 5feet-cyclic adenosine monophosphate (cAMP). In some mammalian cyclic nucleotide systems, generation of cAMP is a complex process involving a hormone receptor, stimulatory (Ns) and inhibitory (Ni) guanidine nucleotide regulatory proteins and the catalytic subunit of adenylate cyclase. In the present studies, the role and interaction of the VP receptor, the putative Ns and Ni regulatory proteins and the catalytic subunit of adenylate cyclase in mediating the osmotic water permeability effect of VP will be examined. These studies will be carried out in microdissected rabbit cortical collecting tubules in which osmotic water flux and adenylate cyclase will be measured. First the effect of probes which selectively stimulate or inhibit the VP receptor (stimulation with VP, inhibition with d(CH2)5Tyr(Et)-VAVP), the Ns unit (stimulation with cholera toxin), the Ni unit (stimulation with guanosine 5 feet-(Beta Gamma-imsido)triphosphate, inhibition with pertussis toxin) and the catalytic subunit (stimulation with forskolin, inhibition with 2 feet, 5 feet dideoxyadenosine) on basal and VP-stimulated osmotic water flux and adenylate cyclase will be performed. Subsequently the effect of altered cationic (Mg++, Mn++, Na+, K+, Li+) tubular environment and toxic and ischemic renal injury on collecting tubular physiologic and biochemical response to VP will be examined. If defects in VP responses are observed, osmotic water flux and adenylate cyclase responses to the above noted probes will allow assessment of the pathogenetic role and site of altered cAMP generation. Together these studies will contribute to our understanding of the mechanism of hydroosmotic effect of VP on mammalian collecting tubule in health and disease.

血管加压素（VP）增加肾功能的作用管状水渗透性在保持身体水分方面至关重要体内平衡 VP的水渗透作用依赖于细胞内产生3英尺5英尺环磷酸腺苷（cAMP）。在一些哺乳动物环核苷酸系统，cAMP的产生是一个复杂的涉及激素受体、刺激性（Ns）和抑制性（Ni）的过程胍核苷酸调节蛋白和催化亚基腺苷酸环化酶在目前的研究中， VP受体，推定的Ns和Ni调节蛋白和催化腺苷酸环化酶亚基介导渗透水通透性 VP的效果将被检查。这些研究将在显微解剖的家兔皮质集合小管，其中渗透水将测量流量和腺苷酸环化酶。首先是探针的影响其选择性地刺激或抑制VP受体（用 VP，用d（CH 2）5 Tyr（Et）-VAVP抑制），Ns单位（用霍乱毒素），Ni单位（用鸟苷5英尺-（β-氨基丁酸）刺激 γ-咪唑啉）三磷酸盐，用百日咳毒素抑制）和催化亚基（用毛喉素刺激，用2英尺抑制，5英尺抑制）足双脱氧腺苷）对基础和VP刺激的渗透水通量的影响，将进行腺苷酸环化酶检查。随后，改变的效果阳离子（Mg++、Mn++、Na+、K+、Li+）管状环境和毒性，缺血性肾损伤对集合管生理生化影响将对VP的响应进行检查。如果观察到VP响应中的缺陷，渗透水通量和腺苷酸环化酶对上述的反应探针将允许评估改变的致病作用和位点。 cAMP生成。这些研究将有助于我们 VP对哺乳动物水渗透作用机制的认识健康和疾病中的集合小管。