Renal Function in Vertebrates

这个项目涉及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，以及离子和水排泄的调节。在这些广泛的领域内，调查将涉及以下研究的继续：1)带负电的有机物质（有机阴离子）的肾小管运输的机制和调节，主要是荧光素（一种荧光化合物，其运输过程中可以观察到），以及带正电的有机物质（有机阳离子），主要是四乙基铵（TEA）；2)调节肾小管细胞内的pH值（即酸或碱）；3)肾小管对滤过液重吸收的机制和调控。这些研究集中在爬行动物的肾脏上，它们有简单的肾小管结构，以及鸟类的肾脏上，它们的肾小管范围从简单的、表面的爬行动物的到深层的、复杂的哺乳动物的。有机分子的肾小管运输在消除许多有毒外源性物质和调节重要内源性物质浓度方面起着特别重要的作用。在爬行动物和鸟类中，这些有机分子运输的细胞步骤和管状转运部位表现出相当大的差异，这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起重要作用，这在爬行动物和爬行动物型鸟类小管的近端部分表现出相似性，而在爬行动物和哺乳动物型鸟类小管的近端部分表现出差异。过滤液的净管重吸收调节对维持正常的流体平衡至关重要。禽肾中不同的小管种群似乎存在差异，这可能与滤过率及其调节的差异有关。在爬行动物和鸟类肾脏单位之间以及鸟类肾脏单位种群之间，流体重吸收与溶质重吸收的耦合可能存在显著差异，这种耦合可能与过滤速率的变化以及有机分子的消除有关。这些研究的方法将主要涉及分离的灌注和非灌注肾小管的工作，并将利用定量光学技术和同位素技术来评估转运速率、细胞内转运步骤和细胞内ph。液体重吸收过程的评估将涉及对被重吸收的液体的直接定性和定量测量。这些结果将提供有关有机分子运输和液体重吸收的机制和调控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相关的重要信息。这些信息将有助于了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。

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.