V. Borner et al., TRANSPORT OF AMINO-ACID ARYL AMIDES BY THE INTESTINAL H+ PEPTIDE COTRANSPORT SYSTEM, PEPT1/, European journal of biochemistry, 255(3), 1998, pp. 698-702
Transport of amino acid aryl amides by the intestinal H+/peptide sympo
rter (PEPT1) was studied in Caco-2 cells and in Xenopus laevis oocytes
expressing human PEPT1. Several amino acid amides were able to inhibi
t the uptake of [C-14]glycylsarcosine in Caco-2 cells. Ala-4-nitroanil
ide (K-i = 0.08 mM), Phe-4-nitroanilide (K-i = 0.09 mM) and Ala-4-phen
ylanilide (K-i = 0.03 mM) were accepted as substrates with equal or hi
gher affinity than natural Ala-Xaa dipeptides. Ala-anilide (K-i = 2.9
mM), Ala-7-amido-4-methylcoumarin (K-i = 0.2 mM), Ala-4-chloroanilide
(K-i = 0.3 mM) and Ala-4-methylanilide (K-i = 0.3 mM) were also recogn
ized by PEPT1 as substrates. In contrast, alanine, Ala-amide, Phe-amid
e, Ala-methyl ester, Ala-4-nitrobenzyl ester and Ala-methylamide were
not recognized (K-i > 20 mM). In X. laevis oocytes, transport of Ala-4
-nitroanilide, Ala-7-amido-4-methylcoumarin, Ala-4-methylanilide and A
la-anilide was associated with transfer of positive charge and the cur
rents were saturable with respect to substrate concentration (K-0.5 va
lues: 0.1, 0.2, 0.8 and 3.1 mM, respectively). The currents induced by
Ala-4-methylanilide were saturable with respect to the substrate conc
entration and influenced by the membrane potential. The affinity of th
e transporter for Ala-4-methylanilide was also found to be influenced
by the membrane potential. We conclude that the intestinal H+/peptide
cotransport system PEPT1 accepts amino acid aryl amides as substrates.