Stimulation of weak organic acid uptake in rat renal tubules by cadmium and nystatin.
The uphill uptake of a weak organic acid, fluorescein, in superficial proximal tubules of the rat kidney was stimulated by CdCl2 (0.1 mM) or nystatin (20 microM) in the absence of metabolic substrates in the incubation medium. The stimulation could be observed during the initial period of incubation (up to 30 min) only and was prevented completely by ouabain (0.1 mM), fluoroacetate (1 mM), malonate (10 mM), alpha-cyano-4-hydroxycinnamate (0.1 mM), phenylpyruvate (1 mM), D-malate (2 mM) or phenazine methosulfate (20 microM). In the renal cortex fragment suspension, both Cd2+ and nystatin increased the ouabain-sensitive, basal oxygen consumption and inhibited the rate of glucose production from pyruvate, but not from lactate. In the presence of lactate (0.5-5 mM) in the incubation medium, Cd2+ and nystatin rather inhibited fluorescein uptake, while externally added pyruvate did not influence their stimulatory effects. Taken together, these data suggest that both activation of the tricarboxylic acid cycle and export of reducing equivalents from the mitochondria to the cytosol are necessary for the stimulatory effects of Cd2+ and nystatin on the weak organic acid uptake to develop.
Nikiforov
A A
AA
Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St Petersburg.
Ostretsova
I B
IB
D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002104:Cadmium / Q000494:pharmacology*; D002952:Citric Acid Cycle / Q000187:drug effects / Q000502:physiology; D003373:Coumaric Acids / Q000494:pharmacology; D019793:Fluorescein; D005452:Fluoresceins / Q000378:metabolism*; D005463:Fluoroacetates / Q000494:pharmacology; D066298:In Vitro Techniques; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism; D008293:Malates / Q000494:pharmacology; D008297:Male; D008314:Malonates / Q000494:pharmacology; D008773:Methylphenazonium Methosulfate / Q000494:pharmacology; D009761:Nystatin / Q000494:pharmacology*; D010042:Ouabain / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D010667:Phenylpyruvic Acids / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000502:physiology
D003373:Coumaric Acids; D005452:Fluoresceins; D005463:Fluoroacetates; D008293:Malates; D008314:Malonates; D010667:Phenylpyruvic Acids; D002104:Cadmium; D009761:Nystatin; C007175:alpha-cyano-4-hydroxycinnamate; D008773:Methylphenazonium Methosulfate; D010042:Ouabain; C030298:malic acid; C030290:malonic acid; D000254:Sodium-Potassium-Exchanging ATPase; D019793:Fluorescein; C031606:phenylpyruvic acid