title: Contraluminal para-aminohippurate (PAH) transport in the proximal tubule of the rat kidney. II. Specificity: aliphatic dicarboxylic acids.
abstract: In order to study the specificity for contraluminal para-aminohippurate (PAH) transport, the inhibitory potency of aliphatic dicarboxylates on 3H-PAH influx, as well as the inhibitory effect on 35SO4(2-)- and 3H-succinate influx, from the interstitium into cortical tubular cells in situ has been determined. The following was found: Testing a homologous series of dicarboxylates--ranging from the 2 C oxalate to the 10 C sebacate--PAH transport was inhibited by succinate (app. Ki 1.35 mmol/l), and all longer dicarboxylates, with high potency (app. Ki 0.05--0.35 mmol/l). Sulfate transport was inhibited only by oxalate (app. Ki 1.1 mmol/l), while dicarboxylate transport was inhibited by succinate, glutarate, adipate and pimelate with decreasing potency (app. Ki 0.04, 0.24, 0.91, 4.0 mmol/l, respectively). PAH transport was inhibited by succinate and glutarate with high potency (app. Ki 1.35 and 0.05 mmol/l), by the correspondent monomethylester to a lesser extent (app. Ki 1.7 and 0.74 mmol/l), but not by the dimethylester. On the other hand, the semialdehyde of succinate with a Ki-value of 1.2 mmol/l, had the same inhibitory potency as succinate itself, while the dialdehyde of glutarate (app. Ki 1.4 mmol/l) was much less potent as glutarate. Introduction of an oxo-, methyl- or sulfhydroxyl-group group onto the 2-position of succinate, or of an oxo-group onto the 2-position of glutarate moderately augmented the inhibitory potency against PAH-uptake. However, introduction of a 2-hydroxy group onto succinate or glutarate in the L-position reduced the inhibitory potency more than in the D-position. Introduction of two methyl-, sulfhydryl- or hydroxyl-groups in the 2-3 position of succinate reduced or abolished its inhibitory potency. The introduction of a 2-amino group onto succinate or glutarate abolished its effect on PAH transport.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000618:Aminohippuric Acids / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D003998:Dicarboxylic Acids / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013386:Succinates / Q000378:metabolism; D019802:Succinic Acid; D013431:Sulfates / Q000378:metabolism; D010130:p-Aminohippuric Acid / Q000378:metabolism*
chemical_list: D000618:Aminohippuric Acids; D003998:Dicarboxylic Acids; D013386:Succinates; D013431:Sulfates; D019802:Succinic Acid; C039138:methylsuccinic acid; D010130:p-Aminohippuric Acid