Renal Function in Vertebrates

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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. ***