title: Effect of maleate on tubular protein reabsorption in dog kidneys.
abstract: To examine the effects on protein and electrolyte reabsorption of reducing the energy supply to the proximal tubules, an inhibitor of the citric acid cycle, maleate (600 mg.kg-1), was administered to anesthetized dogs during continuous ethacrynic acid infusion. One hour after infusion, maleate reduced renal oxygen consumption from 128 +/- 3 to 48 +/- 6 mumol.min-1. Comparisons at similar GFR showed that maleate reduced bicarbonate reabsorption by 65%, chloride reabsorption by 60% and phosphate reabsorption by 90%. Tubular reabsorption of lysozyme, determined by the 'trapped-label' method, was reduced by 97%. Total protein excretion in urine increased from 0.12 to 1.0 mg.min-1 and was not associated with a significant increase in brush border and lysosome marker enzymes. However, by superimposing a carbonic anhydrase inhibitor, acetazolamide (100 mg.kg-1), electrolyte reabsorption was slightly further reduced but protein excretion increased to 2.7 mg.min-1, coincidentally with a dramatic increase in enzyme excretion: approximately 20-fold in the brush border enzymes, alanine aminopeptidase and alkaline phosphatase, and 10-fold in the lysosomal enzymes, acid phosphatase and N-acetyl-beta-glucosaminidase. Our data indicate that maleate stops protein reabsorption without signs of acute tubular damage, whereas subsequent administration of acetazolamide results in tubular desquamation and albumin leakage.
authors.affiliation: Institute for Experimental Medical Research, University of Oslo, Ullevaal Hospital, Norway.
authors.forename: J
authors.initials: J
authors.lastname: Hysing
authors.forename: J
authors.initials: J
authors.lastname: Ostensen
authors.forename: H
authors.initials: H
authors.lastname: Tolleshaug
authors.forename: F
authors.initials: F
authors.lastname: Kiil
mesh_terms: D000042:Absorption; D000086:Acetazolamide / Q000494:pharmacology; D000818:Animals; D004285:Dogs; D004357:Drug Synergism; D007684:Kidney Tubules / Q000378:metabolism*; D008298:Maleates / Q000494:pharmacology*; D011506:Proteins / Q000493:pharmacokinetics*
chemical_list: D008298:Maleates; D011506:Proteins; C030272:maleic acid; D000086:Acetazolamide