Contraluminal para-aminohippurate (PAH) transport in the proximal tubule of the rat kidney. VI: Specificity ― Amino acids, their N-methyl-, N-acetyl- and N-benzoylderivatives; glutathione- and cysteine conjugates, di- and oligopeptides

• Published in: Pflügers Archiv 1989-12, Vol.415 (3), p.342-350
• Main Authors: ULLRICH, K. J, RUMRICH, G, WIELAND, T, DEKANT, W
• Format: Article
• Language: English
• Subjects: Acetylation; Amino Acid Sequence; Amino Acids - metabolism; Aminohippuric Acids - metabolism; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Animals; Biological and medical sciences; Biological Transport - drug effects; Cysteine - metabolism; Dipeptides - metabolism; Fundamental and applied biological sciences. Psychology; Glutathione - metabolism; Kidney Tubules, Proximal - metabolism; Male; Methylation; Molecular Sequence Data; Oligopeptides - metabolism; p-Aminohippuric Acid - metabolism; Rats; Rats, Inbred Strains; Vertebrates: urinary system
• ISSN: 0031-6768; 1432-2013
• DOI: 10.1007/BF00370886

In order to evaluate the specificity of the renal contraluminal PAH transport system for amino acids, oligopeptides and their conjugates, the inhibitory potency of these substances against contraluminal [3H] PAH influx has been determined. For this, inhibition of 3H-PAH flux from the interstitium into cortical tubular cells of the rat kidney in situ has been measured. Apparent Ki values were evaluated by a computer program assuming competitive inhibition. Unconjugated amino acids (glycine, cysteine, alanine, leucine, phenylalanine, tyrosine, aspartate, glutamate, arginine, ornithine and lysine) do not inhibit [3H] PAH influx. The very hydrophobic tryptophan, however, does. N-alpha-methylation does not change this behaviour. N-alpha-acetylation does not evoke interaction with the PAH transporter when it occurs with glycine, cysteine (to yield mercapturic acid), arginine, ornithine and lysine. However, it renders alanine, leucine, phenylalanine, tryptophan, L-aspartate moderately, and L-glutamate strongly, inhibitory. The acetylated D-isomers of alanine, leucine and phenylalanine exert a higher inhibitory potency compared with the respective L-isomers. N-alpha-benzoylation of L-lysine is ineffective. N-alpha-benzoylation, however, evokes interaction with the PAH transporter, when it occurs with ornithine less than arginine less than histidine less than glycine = leucine less than alanine = phenylalanine = aspartate = glutamate. Dipeptides interact with the PAH transporter according to their hydrophobicity (Nozaki scale down to 0.9, Fauchère scale up to 1.0). N-acetylation does not change this behaviour. Hydrophobicity also renders oligopeptides, as angiotensin II, inhibitory against PAH transport. Similarly the anionic angiotensin I converting enzyme inhibitors Captopril, Enalapril and Ramipril inhibit contraluminal PAH influx.