The mechanism of maleic acid nephropathy: investigations using brush border membrane vesicles.
Brush border membrane vesicles from dog kidney proximal tubule have been used to investigate the pathogenesis of glucosuria resulting from maleic acid nephropathy. Direct exposure of brush border vesicles to 9 mM maleic acid for up to 36 minutes has no effect of the Na+-dependent D-glucose uptake mechanism. Brush border membrane vesicles were then prepared from dogs in which glucosuria had first been induced by prior administration of maleic acid (250 mg/Kg body weight). The timed uptake of D- and L-glucose was measured in the presence in the presence of both Na+ chemical and electropotential driving forces and compared to uptake in vesicles prepared from matched control kidneys from the same animal. Maleic acid treated and control vesicles were also assayed for the presence of the Na+-dependent high affinity phlorizin receptor. Our results indicate that there is no alteration in behavior of the Na+-dependent transport system for glucose at the brush border membrane in the model Fanconi state produced by maleic acid. Moreover, there is no change in the coupling of sugar transport either to the Na+ chemical or the electrical potential gradient across the brush border membrane. These studies imply that further efforts to define the pathogenesis of maleic acid nephropathy are probably best carried out using intact tissue or cells because the molecular defect is at the level of the Na+ pump and/or at some intracellular site affecting production of ATP.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism*; D004285:Dogs; D005947:Glucose / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007700:Kinetics; D008298:Maleates / Q000494:pharmacology*; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000494:pharmacology; D013861:Thiocyanates / Q000494:pharmacology; D014634:Valinomycin / Q000494:pharmacology
D008298:Maleates; D013861:Thiocyanates; D014634:Valinomycin; D012964:Sodium; D005947:Glucose