Renal Function in Vertebrates

脊椎动物的肾功能

• 批准号: 9814448
• 负责人: William Dantzler
• 金额: $ 42.5万
• 依托单位: University of Arizona
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-01 至 2005-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9814448&HistoricalAwards=false
• 关键词: Renal; Function; Vertebrates

9814448DantzlerThis project involves comparative studies of kidney function in vertebrates. The studies emphasize the general area of transport by the kidney tubules (the primary functioning units in the kidney), particularly of organic substances, and the regulation of excretion of ions and water. Within these broad areas, the investigations will involve continuations of studies on: 1) the mechanisms and regulation of kidney tubular transport of negatively charged organic substances *organic anions), primarily fluorescein (a fluorescent compound whose transport can be observed while it is occurring), and of positively charged organic substances (organic cations), primarily tetraethylammonium (TEA); 2) the regulation of the pH (i.e., the acid or base) within the cells of renal tubules; and 3) the mechanisms and regulation of reabsorption of filtered fluid by the renal tubules. These studies concentrate on reptilian kidneys, with their simple renal tubule structure, and on avian kidneys, with their kidney tubules ranging from simple, superficial reptilian-like ones to deep, complex mammalian-like ones. The renal tubular transport of organic molecules plays a particularly important role in eliminating many toxic exogenous substances and in regulating the concentrations of important endogenous substances. The cellular steps in transport and the tubular sites of transport of these organic molecules show considerable variation in reptiles and birds and may relate to the types of tubules and their function in the transport of other organic molecules and ions and water. Regulation of intracellular pH, which shows similarities in the proximal portions of reptilian tubules and reptilian-type avian tubules and differences in proximal portions of reptilian-type and mammalian-type avian tubules, may also play an important role in determining the transport of organic molecules. The regulation of net tubular reabsorption of filtered fluid is essential to maintaining normal fluid balance. It appears to show variation sin the different tubules populations in the avian kidney and this may relate to differences in filtration rate and its regulation. The coupling of fluid reabsorption to solute reabsorption may differ significantly between reptilian and avian nephrons and among populations of avian nephrons and this coupling may relate to changes in filtration rate as well as the elimination of organic molecules. The approach to these studies will involve work primarily with isolated perfused and nonperfused renal tubules and will take advantage of quantitative optical techniques as well as isotopic techniques to evaluate rates of transport, intracellular transport steps, and intracellular pH. Evaluation of the process of fluid reabsorption will involve direct qualitative and quantitative measurements of the fluid being reabsorbed. The results should supply significant information on the mechanisms and regulation of the transport of organic molecules and the reabsorption of fluid and how these processes relate to structural and other functional differences in reptilian and avian kidneys. The information will help in understanding how these species survive in hostile environments and the ways in which their kidneys help them deal with current and potential environmental toxins.

这个项目涉及对脊椎动物肾脏功能的比较研究。这些研究强调肾小管(肾脏的主要功能单位)运输的一般区域，特别是有机物质的运输，以及离子和水的排泄的调节。在这些广泛的领域内，调查将涉及以下方面的继续研究：1)带负电荷的有机物质(如有机阴离子)，主要是荧光素(一种在发生时可观察到其转运的荧光化合物)和带正电荷的有机物质(有机阳离子，主要是四乙基铵(TEA))在肾小管中转运的机制和调节；2)肾小管细胞内pH值(即酸或碱)的调节；3)肾小管重吸收滤液的机制和调节。这些研究集中于爬行动物肾脏和鸟类肾脏，爬行动物肾脏具有简单的肾小管结构，鸟类肾脏的肾脏小管从简单的、浅层的爬行动物肾脏到深层的、复杂的哺乳动物肾脏不等。有机分子的肾小管转运在清除许多有毒的外源性物质和调节重要内源性物质的浓度方面发挥着特别重要的作用。这些有机分子的细胞转运步骤和管状转运部位在爬行动物和鸟类中表现出相当大的差异，可能与小管的类型及其在其他有机分子、离子和水的运输中的功能有关。细胞内pH的调节也可能在决定有机分子的运输中发挥重要作用。细胞内pH的调节在爬行动物类型的小管和爬行动物类型的鸟类小管的近端部分显示出相似之处，而在爬行动物类型的鸟类小管的近端部分显示出不同之处。调节滤液的净肾小管重吸收对维持正常的液体平衡至关重要。在禽类肾脏的不同小管群中，它似乎表现出差异，这可能与过滤速度及其调节的差异有关。流体重吸收与溶质重吸收的耦合在爬行动物和鸟类之间以及鸟类种群之间可能有显着差异，这种耦合可能与过滤速度的变化以及有机分子的清除有关。这些研究的方法将主要涉及分离的灌流和非灌流的肾小管，并将利用定量光学技术以及同位素技术来评估转运速度、细胞内转运步骤和细胞内pH。对流体重吸收过程的评价将包括对被重吸收的流体进行直接的定性和定量测量。这些结果应该提供关于有机分子运输和液体重吸收的机制和调节的重要信息，以及这些过程如何与爬行动物和鸟类肾脏的结构和其他功能差异有关。这些信息将有助于理解这些物种如何在恶劣的环境中生存，以及它们的肾脏如何帮助它们处理当前和潜在的环境毒素。