fumaric-acid and methylglucoside

Glucose and other hexoses as well as amino acids have been shown to inhibit the renal transport of phosphate (Pi). Although studies with renal brush border membrane vesicles showed that such an inhibitory effect on Pi transport is due to the dissipation of the Na electrochemical gradient, the mechanism(s) responsible for such an action in the intact cell is not clear. The present study examined the effects of tricarboxylic acid (TCA) cycle intermediates (succinate and fumarate) and acetate on the uptake of Pi and alpha-methylglucoside (AMG) at 37 degrees C by intact rabbit renal cells. These TCA cycle compounds significantly (p less than 0.05) inhibited the uptake of both Pi and AMG. In the presence of 5-10 mM succinate the ATP content of the renal cells increased by 40% (p less than 0.02). Inhibition of succinate-induced gluconeogenesis by 3-mercaptopicolinic acid did not modify the inhibition of Pi uptake. Studies with renal brush border membrane vesicles showed that succinate inhibited Pi uptake at 15 and 60 s but not at 1 s and only under conditions of Na gradient (outside greater than inside). Succinate did not inhibit Pi uptake during Na equilibrium conditions. The data demonstrate that the succinate-induced inhibition of the Pi uptake by intact proximal renal cells is not due to competition for metabolic energy, is not related to stimulation of gluconeogenesis nor due to allosteric interaction between Pi carrier and succinate transporter. The results support the notion that the inhibition of Pi uptake by succinate in the intact renal cell is due to dissipation of the Na chemical gradient.

Topics: Animals; Citric Acid Cycle; Fumarates; Glucose; Kidney; Male; Methylglucosides; Microvilli; Phosphates; Picolinic Acids; Rabbits; Sodium; Succinates; Succinic Acid

We investigated the viability of isolated rabbit renal cortical cells and the effect of metabolic intermediates on phosphate uptake. Glucose production and its stimulation by hormones was similar to that previously reported for renal tubules. The uptake of alpha-methylglucoside and phosphate was reduced by 90% when sodium was removed from the media. ATP content of the cells was 9.4 +/- 0.7 nmol/mg protein. Succinate and fumarate stimulated phosphate uptake in a dose-dependent manner by 30-60%. Valeric acid (1 mM) and butyric acid (10 mM) stimulated phosphate uptake by 20-30%. Glucose and fructose stimulated phosphate uptake by 18% but only at low concentrations (0.1 mM). Exogenous nucleotides had no effect on phosphate uptake at 0.2 mM, but inhibited 2.4 mM phosphate uptake at 2 mM. We conclude: rabbit renal cortical cells in suspension are metabolically and functionally viable; tricarboxylic acid cycle and glycolytic intermediates as well as short chain fatty acids can stimulate phosphate uptake, and exogenous nucleotides are hydrolyzed to produce free phosphate causing inhibition of isotopic phosphate uptake.

Topics: Animals; Fumarates; Gluconeogenesis; Glycolysis; Isoproterenol; Kidney Cortex; Male; Methylglucosides; NAD; Nucleotides; Phosphates; Rabbits; Succinates; Succinic Acid; Time Factors