Renal Function in Vertebrates

拟议的研究涉及肾脏排泄水、无机物和有机物质的机制和调节。它们涉及对血液滤液产生速率的调节以及有机和无机物通过肾小管细胞移动的机制，或者从最初的滤液回到灌注这些细胞的血液中，或者从血液灌注这些细胞到最初的滤液中。被研究的有机物是那些以带正电分子存在的有机物（主要是外源性神经阻断剂四乙基铵和内源性烟酸代谢产物n1 -甲基烟酰胺）和那些以带负电分子存在的有机物（主要是外源性化合物对氨基马嘌呤酸酯和内源性氮代谢终产物尿酸盐）。这些研究利用了爬行动物相对简单的肾脏，其中一些物质通过小管细胞的运动（或运动的某些特征）比哺乳动物更明显，以及鸟类复杂的肾脏，部分类似于爬行动物的肾脏，部分类似于哺乳动物的肾脏。实验方法是一种综合的方法，探索膜细胞和整个器官水平的功能。这些研究对于了解肾脏如何使动物在特定环境中生存并适应不断变化的环境具有重要意义。在面对地球环境的重大变化时，就采取策略确保动物种群的生存而言，这种理解尤为重要。这种策略对人类也很重要。这些研究还将对野生或家养动物的肾脏处理有机环境污染物（包括许多有毒化合物）的方式提供实质性的见解。这种理解也适用于人类的肾脏，不仅就通常有毒的物质而言，而且就过量存在时可能有毒的治疗药物而言。最后，这些研究将提供有关肾脏消除尿酸盐的方式的信息，尿酸盐是人类和其他动物肾结石形成的重要物质。//

The proposed studies concern the mechanisms and the regulation of those mechanisms whereby the kidneys excrete water, inorganic substances, and organic substances. They involve the regulation of the rate of production of a filtrate of the blood and the mechanisms by which organic and inorganic substances are moved across renal tubule cells, either from the initial filtrate back into the blood perfusing these cells or from the blood perfusing these cells into the initial filtrate. The organic substances being studied are those that exist as positively charged molecules (primarily the exogenous nerve blocking agent, tetraethylammonium, and the endogenous product of nicotinic acid metabolism, N1-methylnicotinamide) and those that exist as negatively charged molecules (primarily the exogenous compound, p- aminohippurate, and the endogenous end product of nitrogen metabolism, urate). These studies take advantage of the relatively simple kidneys of reptiles in which the movement (or some characteristic of the movement) of some substances across the tubule cells is more pronounced than in mammals, and the complex kidneys of birds, which in part resemble the kidneys of reptiles and in part resemble the kidneys of mammals. The experimental approach is an integrative one that explores function at the membrane cell, and whole organ levels. These studies are important for understanding the way in which the kidneys permit animals to survive in specific environments and to adapt to changing environments. This understanding is particularly important in terms of adopting strategies to insure the survival of animal populations in the face of major changes in the earth's environment. Such strategies may also be important to human populations. These studies will also provide substantial insight into the way in which the kidneys in wild or domestic animals populations handle organic environmental pollutants, including many toxic compounds. This understanding applies also to human kidneys, not only in terms of normally toxic substances but also in terms of therapeutic agents that can be toxic when present in excess. Finally, these studies will provide information on the way in which the kidneys eliminate urate, an important substance in renal stone formation in humans and other animals. //