Gluconeogenesis and phosphate reabsorption in isolated lactate- or pyruvate-perfused rat kidneys

Recent experiments suggest that cytoplasmic free NAD inhibits renal phosphate reabsorption and that gluconeogenesis, by increasing NAD concentration, inhibits phosphate reabsorption. To examine these relationships further we measured phosphate reabsorption by isolated kidneys perfused with either lactate or pyruvate. Lactate perfusion increased the ratio of the cytoplasmic redox couple (glycerol-3-phosphate/dihydroxyacetone phosphate) in snap-frozen kidneys 3-fold relative to the ratio with pyruvate perfusion (p less than 0.001). Inulin clearance and fractional phosphate reabsorption were lower with lactate than with pyruvate perfusion. Phosphate reabsorption decreased throughout the lactate perfusion but was constant for 1 h of pyruvate perfusion. Basal and norepinephrine (NE)-stimulated gluconeogenesis were lower with lactate than with pyruvate perfusion. With lactate and pyruvate perfusions, NE induced equal increases in fractional sodium reabsorption, although only with pyruvate perfusion was there increased phosphate reabsorption. In these experiments, oxidative phosphorylation, not cytoplasmic free NAD concentrations, influenced phosphate reabsorption, and NE-stimulated gluconeogenesis was associated with increased phosphate reabsorption.