title: Facilitated diffusion of urate in avian brush-border membrane vesicles.
abstract: Membrane transport pathways mediating transcellular secretion of urate across the proximal tubule were investigated in brush-border membrane vesicles (BBMV) isolated from avian kidney. An inside-positive K diffusion potential induced a conductive uptake of urate to levels exceeding equilibrium. Protonophore-induced dissipation of membrane potential significantly reduced voltage-driven urate uptake. Conductive uptake of urate was inhibitor sensitive, substrate specific, and a saturable function of urate concentration. Urate uptake was trans-stimulated by urate and cis-inhibited by p-aminohippurate (PAH). Conductive uptake of PAH was cis-inhibited by urate. Urate uptake was unaffected by an outward alpha-ketoglutarate gradient. In the absence of a membrane potential, urate uptake was similar in the presence and absence of an imposed inside-alkaline pH gradient or an outward Cl gradient. These observations suggest a uniporter-mediated facilitated diffusion of urate as a pathway for passive efflux across the brush border 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; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D004058:Diffusion; D006863:Hydrogen-Ion Concentration; D007476:Ionophores / Q000494:pharmacology; D007656:Ketoglutaric Acids / Q000378:metabolism / Q000493:pharmacokinetics; D007687:Kidney Tubules, Proximal / Q000737:chemistry / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology; D008871:Microvilli / Q000737:chemistry / Q000378:metabolism*; D027361:Organic Anion Transporters; D013347:Subcellular Fractions / Q000737:chemistry / Q000378:metabolism; D014422:Turkeys; D014527:Uric Acid / Q000378:metabolism* / Q000493:pharmacokinetics; D010130:p-Aminohippuric Acid / Q000493:pharmacokinetics
chemical_list: D002352:Carrier Proteins; D002712:Chlorides; D007476:Ionophores; D007656:Ketoglutaric Acids; D027361:Organic Anion Transporters; C103862:urate transporter; D014527:Uric Acid; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D010130:p-Aminohippuric Acid