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. //
