Kinetics of renal aspartate reabsorption and its inhibition by metals in the intact rat kidney.

A modified clearance technique originally developed for the intact rabbit was adapted for use in the intact rat; it permits measurement of maximum tubular capacity (Tm) and half-saturation constant (KM) without the need for high systemic plasma levels and long equilibrating infusions of the solute under study. In this manner, Tm and KM for aspartate reabsorption were determined. Subsequently, we compared these kinetics constants to renal aspartate Tm and KM values in the literature derived from single tubule studies, and analyzed the nephrotoxicity of nickel and cadmium. Aspartate KM and Tm in the intact rat were 6.1 mM and 5.8 mumole/g cortex/min respectively; in contrast, work with single tubules led to KM aspartate of 0.1 mM and Tm aspartate of 20.0 mumole/g cortex/min. The discrepancy between the two sets of results reemphasizes the difficulty in extrapolating from single tubules to intact kidney; presumably tubular heterogeneity accounts for these differences. Aspartate reabsorption was also measured in rats injected intraperitoneally with 20 mumole nickel or cadmium/kg body weight 36 to 40 hr previously. At renal nickel or cadmium concentrations of approximately 10 micrograms/g kidney glomerular filtration rate and aspartate Tm were significantly decreased while aspartate KM was not affected. The effects of the metals resemble a noncompetitive type of inhibition of aspartate reabsorption.