Transport of organic compounds in renal plasma membrane vesicles of cadmium intoxicated rats

Abstract

Effects of cadmium intoxication on renal transport systems for various organic compounds were studied. Subcutaneous injections of CdCl2 (2 mg Cd/kg.day) for two to three weeks induced marked polyuria, glycosuria, and proteinuria without altering glomerular filtration rate. In renal cortical brush border membrane vesicles (BBMV) isolated from cadmium treated rats, Na(+)-dependent D-glucose uptake was markedly attenuated, and this was due to reduction in Vmax and not Km. Likewise, Na(+)-driven L-glutamate transport and H(+)-driven tetraethylammonium transport were significantly reduced. In renal cortical basolateral membrane vesicles (BLMV) of cadmium intoxicated rats, Na(+)-dependent succinate transport was drastically reduced. These results indicate that cadmium intoxication impairs various transport systems for organic compounds in the brush border and basolateral membranes of proximal renal tubules.

Renal type II Na/Pi-cotransporter is strongly impaired whereas the Na/sulphate-cotransporter and aquaporin 1 are unchanged in cadmium-treated rats

“…The Na+-gradient-driven uptake in control vesicles was slightly above the equilibrium for [35S], and twofold and sixfold above equilibrium for [3Hi-glucose and [32p], respectively. In accordance with recent findings by Lee et al [19,20], BBMV from Cd-treated rats exhibited a much lower overshoot for glucose, thus indicating a significant decrease of the Na+-glucose cotransport in these membranes. In contrast, Na+-sulphate cotransport was not inhibited.…”

“…The Cd-treated rats exhibited 3.6-fold higher urine flow and excreted 3 times more urine, 5 times more urine protein and 40% more Pi in the urine. These findings, being typical for chronic Cd intoxication, are similar to those previously published for rats that underwent similar treatment with Cd [2,[17][18][19].…”

“…Although Cd treatment results in a number of acute and chronic effects mainly in the proximal tubule cells [25], it is believed that the primary target for Cd might be the plasma membrane, where the first contact with the toxic cation takes place. As studied in renal cortical brush-border membrane vesicles (BBMV) isolated from Cd-intoxicated rats and rabbits, Na+-D-glucose [19,20], Na+-amino acid [17,19,20], and Na+-phosphate cotransport [2], as well as H+-tetraethylammonium (TEA) countertransport [19] were strongly impaired. The Na+-dependent transports decreased in Vma x without changing the Km value for substrates, thus suggesting that the Cd treatment causes either a decreased number of active transporters or a decreased turnover rate of an unchanged number of transporters, or both, while the affinity for the substrate remains unaffected.…”

“…Nephropathy due to chronic Cd exposure in humans and experimental animals is characterized by defects of reabsorptive and secretory functions in the proximal tubule that clinically resemble acquired Fanconi's syndrome. Glucosuria [1,[17][18][19], proteinuria [1, 4, 17 19], aminoaciduria [1,17,20], phosphaturia [1,2,4,17,18], hypercalciuria [18,26], hyperosmolar polyuria [17][18][19], impared p-aminohippurate (PAH) secretion [18], and increased fractional excretion of Na +, K +, and C1-are common signs of the Cd-damaged kidney in humans and experimental animals.…”

Direct Effect of CoCl2 and NiCl2 on Citrate Uptake by the Rat Renal Brush Border Membrane

“…Other metals, such as, Cd inhibit Na-D-glucose transporter 24) in the rat small intestine brush border membrane, the L-alanine 25) and L-glutamate 26) cotransporter system in the rat renal brush border membrane, and mercury also inhibits the Na + -Pi-cotransporter 27) . In our previous studies, cadmium 28) , inorganic mercury 29) , platinum 30,31) and vanadium 32) were found to inhibit the citrate uptake in a concentration-and time-dependent manner.…”