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  • Title: Contraluminal para-aminohippurate transport in the proximal tubule of the rat kidney. III. Specificity: monocarboxylic acids.
    Author: Ullrich KJ, Rumrich G, Klöss S.
    Journal: Pflugers Arch; 1987 Aug; 409(6):547-54. PubMed ID: 3627969.
    Abstract:
    In order to study the specificity of the contraluminal para-aminohippurate (PAH) transport system, the inhibitory potency of monocarboxylates on the 3H-PAH influx from the interstitium into cortical tubular cells in situ has been determined. The following was found: if a homologous series of fatty acids with increasing chain length is tested, inhibition of contraluminal PAH influx is first seen with valerate (app. Ki 1.4 mmol/l), increasing up to nonanoate (app. Ki 0.06 mmol/l) and remaining in this range up to duodecanoate, the last compound of this series which is sufficiently water-soluble. Similarly, the inhibitory potency of aromatic monocarboxylates increases with increasing hydrophobicity. If the fatty acids are esterified, their inhibitory potency is lost. If they are transformed to the respective aldehydes their inhibitory potency is preserved at a reduced degree. Introduction of a hydrophobic methyl-, ethyl-, or propyl-group increases the inhibitory potency. A beta-, but not an alpha-oxo-group augments the inhibitory potency of phenylpropionate analogs, an OH group diminishes it, and a NH2 group abolishes it. Among phenyl-fatty acids an increase in affinity is observed from phenyl- less than benzoylamine- less than phenoxy- less than benzoyl-acetate and -propionate. All monocarboxylate compounds, so far tested, do not inhibit contraluminal sulfate and Na+/succinate influx. The data indicate that the PAH transporter interacts with monocarboxylates and also with aldehydes which have a hydrophobic moiety. An additional oxo-group facilitates the interaction. Thus, the benzoyl compounds show the highest affinity observed.
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