title: Organic cation transport in human renal brush-border membrane vesicles.
abstract: The renal proximal tubule is responsible for the active elimination of organic cations. Studies in brush-border membrane vesicles (BBMV) suggest that active organic cation transport is mediated by an organic cation-proton antiporter. The goals of this study were to determine whether this transporter is expressed in human kidney and to elucidate its characteristics. Transport of the organic cations N1-[3H]methylnicotinamide (NMN) and [14C]tetraethylammonium (TEA) was determined by rapid filtration in BBMV of donor human kidneys. The uptake of NMN and TEA was driven against a concentration gradient by an outwardly directed proton gradient. NMN uptake was inhibited by the organic cations TEA, NMN, quinine, and cimetidine, but was not affected by p-aminohippuric acid, cephalexin, and polyamines. The electroneutral transport of NMN was characterized by a Km of 0.44 +/- 0.07 mM and a Vmax of 24.4 +/- 15.2 pmol.mg protein-1.s-1. The rate of proton efflux from BBMV increased in the presence of an inwardly directed TEA gradient. Preloading BBMV with NMN or TEA trans-stimulated the initial rate of uptake of TEA. Therefore the human proximal tubule expresses an organic cation-proton antiporter in the brush-border membrane. The antiporter is similar to that described in other mammalian species but shows some differences in its transport characteristics.
authors.affiliation: School of Pharmacy, University of California, San Francisco 94143.
authors.forename: R J
authors.initials: RJ
authors.lastname: Ott
authors.forename: A C
authors.initials: AC
authors.lastname: Hui
authors.forename: G
authors.initials: G
authors.lastname: Yuan
authors.forename: K M
authors.initials: KM
authors.lastname: Giacomini
mesh_terms: D000328:Adult; D001692:Biological Transport; D002412:Cations; D002648:Child; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008871:Microvilli / Q000378:metabolism*; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000378:metabolism; D012044:Regression Analysis; D013050:Spectrometry, Fluorescence / Q000379:methods; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000378:metabolism*
chemical_list: D002412:Cations; D013757:Tetraethylammonium Compounds; D009536:Niacinamide; D019789:Tetraethylammonium; D005947:Glucose; C024058:N(1)-methylnicotinamide