Maleic acid-induced proximal tubulopathy: Na:K pump inhibition.
Maleic acid (MA) administration to experimental animals induces a rapid, reversible, complex dysfunction of the renal tubule resembling Fanconi's syndrome. The intent of this work was to characterize the changes in the Na:K pump along the nephron during the development and recovery from MA injury to better define the site of damage and to correlate the observed changes in Na:K pump function with alterations in metabolic function. Male Sprague Dawley rats were studied before and 2 and 24 h after the injection of MA (100 mg/kg iv). MA induced an early and reversible decline in Na:K pump activity in the proximal convoluted tubule (PCT) from 2,324 +/- 61 to 1,446 +/- 55 pmol/mm.h (P < 0.001). This decrement was transient because enzyme activity returned to near baseline by 24 h after MA administration. The changes in Na:K pump activity were restricted to the PCT because no change in pars rectae, in medullary thick ascending limb, or in medullary collecting tubules was observed. PCT obtained from MA-treated rats 2 h after drug injection showed a decline in 14CO2 formation from radiolabeled glutamine, implying impaired oxidation of the carbon skeleton of the amino acid. This decline was transient with recovery of oxidative rates to normal 24 h after MA administration. It was concluded that a reversible, segment-specific impairment in PCT Na:K pump occurs early after the administration of MA. The decline in PCT Na:K pump activity is paralleled by a decrement in oxidative metabolism and may underlie the many consequences of this model of proximal tubulopathy that are reflections of impairment in sodium-dependent transport processes.
Department of Medicine, Northwestern University, Chicago, IL.
S K
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Mujais
D000251:Adenosine Triphosphatases / Q000032:analysis; D000818:Animals; D003653:Decarboxylation; D005198:Fanconi Syndrome / Q000139:chemically induced* / Q000201:enzymology; D005973:Glutamine / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008298:Maleates / Q000494:pharmacology / Q000633:toxicity*; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*
D008298:Maleates; D005973:Glutamine; C030272:maleic acid; D000251:Adenosine Triphosphatases; D000254:Sodium-Potassium-Exchanging ATPase