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.
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