Contraluminal para-aminohippurate (PAH) transport in the proximal tubule of the rat kidney

Publisher Website
Google Scholar
Abstract
In order to study the specificities of the contraluminal anion transport systems, the inhibitory potency of substituted benzene analogs on influx of [3H]PAH, [14C]succinate, and [35S]sulfate from the interstitium into cortical tubular cells has been determined in situ: (1) Contraluminal [3H]PAH influx is moderately inhibited by benzene-carboxylate and benzene-sulfonate, and strongly by benzene-dicarboxylates,-disulfonates and carboxy-benzene-sulfonates, if the substituents are located at positions 1 and 3 or 1 and 4. The affinity of the PAH transporter to polysubstituted benzoates increases with increasing hydrophobicity, decreasing electron density at the carboxyl group and decreasing pKa. Similar dependencies are observed for phenols. Benzaldehydes which do not carry an ionic negative charge are accepted by the PAH-transporter, if they possess a second partially charged aldehyde or NO2-group. (2) Contraluminal [14C]succinate influx is inhibited by benzene 1,3- or 1,4-dicarboxylates,-disulfonates and 1,3-or 1,4-carboxybenzene-sulfonates. Monosubstituted benzoates do not interact with the dicarboxylate transporter, but NO2-polysubstituted benzoates do. Phenol itself and 2-substituted phenol interact weakly possibly due to oligomer formation. (3) The contraluminal sulfate transporter interacts only with compounds which show a negative group accumulation such as 3,5-dinitro- or 3,5-dichloro-substituted salicylates. The data are consistent with three separate anion transport systems in the contraluminal membrane: The PAH transporter interacts with hydrophobic molecules carrying one or two negative charges (−COO−, −SO 3 − ) or two or more than two partial negative charges (−OH, −CHO, −SO2NH2, −NO2). The dicarboxylate transporter requires two electronegative ionic charges (−COO−, −SO 3 − ) at 5–9 Å distance or one ionic and several partial charges (−Cl, −NO2) at a favourable distance. The sulfate transporter interacts with molecules which have neighbouring electronegative charge accumulation.