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.
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.
Ullrich
K J
KJ
Max-Planck-Institut für Biophysik, Frankfurt/Main, Federal Republic of Germany.
Rumrich
G
G
Wieland
T
T
Dekant
W
W
D000107:Acetylation; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism*; D000618:Aminohippuric Acids / Q000378:metabolism*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003545:Cysteine / Q000378:metabolism; D004151:Dipeptides / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D008745:Methylation; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D010130:p-Aminohippuric Acid / Q000378:metabolism*
D000596:Amino Acids; D000618:Aminohippuric Acids; D000806:Angiotensin-Converting Enzyme Inhibitors; D004151:Dipeptides; D009842:Oligopeptides; D005978:Glutathione; D003545:Cysteine; D010130:p-Aminohippuric Acid