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)带负电荷的有机物质（有机阴离子）的肾小管运输的机制和调节，主要是对氨基马粪酸盐（PAH）、荧光素和尿酸盐，带正电荷的有机物质（有机阳离子），主要是四乙基铵（TEA）；2)细胞内pH （pHi）的调节，特别是与有机阴离子和阳离子的转运有关；3)肾小管对滤过液重吸收的机制及调控。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。有机物质的肾小管运输在消除尿酸盐（鸟类和大多数爬行动物氮代谢的主要排泄终产物）和许多有毒外源性物质以及调节重要内源性物质的浓度方面起着特别重要的作用。在爬行动物和鸟类中，这些有机物质运输的细胞步骤和管状转运部位表现出相当大的差异，这可能与肾小管的类型及其在其他有机物质、离子和水的运输中的功能有关。爬行动物和鸟类肾小管对细胞内pH值的调节可能有很大的不同，这可能在决定这些有机物质的运输中起重要作用。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t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小管之间以及鸟类肾小管种群之间，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物质的消除有关。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肾小管有机分子运输和液体重吸收的机制和调节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。获得的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。＊＊＊

9513892 Dantzler This 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 p-aminohippurate (PAH), fluorescein, and urate, and positively charged organic substances (organic cations), primarily tetraethylammonium (TEA); 2) the regulation of intracellular pH (pHi), especially as it relates to the transport of organic anions and cations; and 3) the mechanisms and regulation of the kidney tubular reabsorption of filtered fluid. 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 kidney tubular transport of organic substances plays a particularly important role in eliminating urate (the major excretory end product of nitrogen metabolism in birds and most reptiles) and 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 substances show considerable variation in reptiles and birds and may relate to the types of renal tubules and their function in the transport of other organic substances and ions and water. The regulation of intracellular pH, which may be quite different in reptilian and avian renal tubules, may play an important role in determining the transport of these organic substances. The regulation of net tubular reabsorption of filtered fluid is essential to maintaining normal fluid balance. It appears to show variations in the different t ubule 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 kidney tubules and among populations of avian kidney tubules and this coupling may relate to changes in filtration rate as well as the elimination of organic substances. 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 kidney tubule 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 obtained 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. ***