Investigations on metabolic modulation of p-aminohippurate accumulation by rabbit renal cortical slices

Preparation and incubation of renal cortical slices from adult, female, New Zealand white rabbit depleted tissue citrate concentration. Acetate (10.0 mM) in the incubation significantly increased slice citrate concentration and p-aminohippurate (PAH) accumulation. Physiological concentrations of citrate increased PAH accumulation and final medium pH. increasing concentrations of citrate produced a biphasic effect on PAH accumulation. These data suggested that citrate may act as an intracellular modulator of organic anion transport. This hypothesis was tested with other stimulators of PAH accumulation. Physiological concentrations of alpha-ketoglutarate or succinate increased slice accumulation of PAH. Higher concentrations of either substrate significantly inhibited PAH accumulation. Final medium pH increased with increased medium concentration of both substrates. alpha-Ketoglutarate (0.5 mM) increased PAH accumulation but had no effect on slice citrate concentration. Glucose did not alter either PAH accumulation or slice citrate concentration. Slices incubated without substrate were depleted of citrate but not of alpha-ketoglutarate. Acetate (1.0 mM) significantly increased slice concentration of both alpha-ketoglutarate and citrate. These data suggested that organic anion transport could be modulated by several metabolic intermediates acting through similar but separate mechanisms.