Arginine is an essential amino acid in neonates and sow milk
is deficient in arginine, therefore neonates heavily rely on de novo arginine synthesis. In piglets,
weaning from sow milk and parenteral nutrition and prematurity in human
increase the arginine requirement to maximize the growth and metabolic process.
PepT1 is necessary for peptide transport, but its activity also appears to
enhance free amino acid absorption via trans-stimulation of the Na+
independent amino acid transporter B0/+/AT. B0/+/AT transports
cationic amino acids such as arginine and lysine. Previously we demonstrated
significantly enhanced arginine uptake from in situ isolated small intestinal
segments that were perfused with arginine (arg) and lysyl-lysine (lys-lys) compared
to arg alone. We speculated that enhanced arginine uptake was facilitated by
PepT-mediated uptake of lys-lys, which increased intracellular lysine
concentration as a result of lys-lys hydrolysis. Higher intracellular lysine
enhanced arginine uptake through the trans-stimulation of the B0/+transporter. Therefore, the objective of
this study was to determine whether the enhanced arg uptake in the presence of
lys-lys can be abolished when co-perfused with the hydrolysis resistant
dipeptide, glycyl-sarcosine (gly-sar). In piglets (d=16-17, N=6) the small intestine was exposed by
laparotomy, and six segments of proximal small intestine were isolated.
Segments were continuously perfused two hours, with one of these six treatments:
1) L-arg  (10 mM) plus 3H-arg
(control)or same arg concentration as control plus either, 2) lys-lys (20 mM),
3) gly-sar (20 mM), 4) lys-lys (20 mM) plus gly-sar (5 mM) 5) lys-lys(20 mM)
plus gly-sar (10 mM) or 6) lys-lys(20 mM) plus gly-sar (20 mM). Disappearance
of 3H-arg and absolute arginine concentration in the perfusate analysis
showed significantly (p<0.05) greater arginine uptake when the loops perfused arg with lys-lys compared to arg alone and arg with gly-sar through the trans-stimulation of B0/+ transporter. Furthermore, arg with lys-lys and gly-sar (20 mM) significantly reduced the arg uptake compared to arg with lys-lys treatment via competitive inhibition of lys-lys uptake due to the high affinity of gly-sar to the Pep T1 transporter.  However, no differences in mucosal free arg was detected.