title: Urate/alpha-ketoglutarate exchange in avian basolateral membrane vesicles.
abstract: Membrane transport pathways for transcellular secretion of urate across the proximal tubule were investigated in avian kidney. The presence of coupled urate/alpha-ketoglutarate exchange was investigated in basolateral membrane vesicles (BLMV) by [(14)C]urate and [alpha-(3)H]ketoglutarate flux measurements. An inward Na gradient induced accumulation of alpha-ketoglutarate of sufficient magnitude to suggest a Na-dicarboxylate cotransporter. An inward Na gradient also induced concentrative accumulation of urate in the presence of alpha-ketoglutarate but not in its absence, suggesting urate/alpha-ketoglutarate exchange. alpha-Ketoglutarate-dependent stimulation of urate uptake was not observed in brush-border membrane vesicles. An outward urate gradient induced concentrative accumulation of alpha-ketoglutarate. alpha-Ketoglutarate-coupled urate uptake was specific for alpha-ketoglutarate, Cl dependent, and insensitive to membrane potential. alpha-Ketoglutarate-coupled urate uptake was inhibited by increasing p-aminohippurate (PAH) concentrations, and alpha-ketoglutarate-coupled PAH uptake was observed. alpha-Ketoglutarate-coupled PAH uptake was inhibited by increasing urate concentrations, and an outward urate gradient induced concentrative accumulation of PAH. These results suggest a Cl-dependent, alpha-ketoglutarate-coupled anion exchange mechanism as a pathway for active urate uptake across the basolateral membrane of urate-secreting proximal tubule cells.
authors.affiliation: Department of Pharmacology, State University of New York, Upstate Medical University, 766 Irving Avenue, Syracuse, NY 13210, USA. grassls@upstate.edu
authors.forename: Steven M
authors.initials: SM
authors.lastname: Grassl
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002250:Carbon Radioisotopes; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D007656:Ketoglutaric Acids / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D007687:Kidney Tubules, Proximal / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D008564:Membrane Potentials / Q000502:physiology; D008871:Microvilli / Q000737:chemistry / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D014316:Tritium; D014422:Turkeys; D014527:Uric Acid / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D010130:p-Aminohippuric Acid / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D002250:Carbon Radioisotopes; D002712:Chlorides; D007656:Ketoglutaric Acids; D014316:Tritium; D014527:Uric Acid; D012964:Sodium; D010130:p-Aminohippuric Acid