Datensatz

Zusammenfassung

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 pK_a. 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.