title: Citrate and succinate transport in proximal tubule cells.
abstract: Urinary citrate, which inhibits calcium nephrolithiasis, is determined by proximal reabsorption via an apical dicarboxylate transporter. Citrate is predominantly trivalent at physiological pH, but citrate(-2) is transported at the apical membrane. We now demonstrate that low-Ca solutions induce transport of citrate(-2) and succinate in opossum kidney cells. With 1.2 mM extracellular Ca, citrate uptake was pH insensitive and not competed by succinate(-2). In contrast, with low extracellular Ca, citrate uptake increased twofold, was inhibited by succinate (and other dicarboxylates), was stimulated by lowering extracellular pH (consistent with citrate(-2) transport), and increased further by lowering extracellular Mg. The effect of Ca was incrementally concentration dependent, between 0 and 1.2 mM. The effect of Ca was not simply complexation with citrate because succinate (which is complexed significantly less) was affected by Ca similarly. Incubation of cells for 48 h in a low-pH media increased citrate transport (studied at control pH) more than twofold, suggesting induction of transporters.
authors.affiliation: Tulane Medical Center and Veterans Affairs Medical Center, New Orleans, Louisiana 70112, USA.
authors.forename: K S
authors.initials: KS
authors.lastname: Hering-Smith
authors.forename: C T
authors.initials: CT
authors.lastname: Gambala
authors.forename: L L
authors.initials: LL
authors.lastname: Hamm
mesh_terms: D000138:Acidosis / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D019343:Citric Acid / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics*; D029382:Dicarboxylic Acid Transporters; D005110:Extracellular Space / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism; D009893:Opossums; D012964:Sodium / Q000502:physiology; D012996:Solutions; D013379:Substrate Specificity; D019802:Succinic Acid / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D002352:Carrier Proteins; D029382:Dicarboxylic Acid Transporters; D012996:Solutions; D019343:Citric Acid; D012964:Sodium; D019802:Succinic Acid; D008274:Magnesium; D002118:Calcium