L-glutamine and l-asparagine stimulate ornithine decarboxylase
activity and proliferation in a porcine jejunal enterocyte line.
Kandil, Hosam M., Robert A. Argenzio, Wunian Chen, Helen M.
Berschneider, Alan D. Stiles, John K. Westwick, Richard A. Rippe,
David A. Brenner, and J. Marc Rhoads.
Department of Pediatrics and Medicine, University of North
Carolina, Department of Physiological Sciences, North Carolina State
University College of Veterinary Medicine, and Center for
Gastrointestinal Biology and Disease, Chapel Hill and Raleigh, NC,
27599 and 27524
APStracts 2:0084G, 1995.
We studied the effect of L-glutamine, the principal intestinal fuel,
on proliferation of a porcine jejunal cell line, IPEC-J2. In cells
synchronized by serum deprivation for 4 h, L-glutamine (GLN)
stimulated ornithine decarboxylase (EC 4.1.1.17, ODC) in a dose- and
time-dependent manner, with maximal effects at 10 mM in 3 h, (p <
0.01). Similar effects were seen for the structurally related amino
acid L-asparagine and serum. The GLN effect on ODC was specific, as
isoosmolar mannitol, glucose, methyl-[beta]-D-glucoside, L
-phenylalanine, ammonia, and aminoisobutyric acid were ineffective.
The alanine aminotransferase inhibitor (aminooxy)acetate (AO)
inhibited the ODC stimulation by GLN in a dose-dependent manner (IC50
= 0.5 mM). AO was not toxic to cells, as determined by propidium
iodide uptake into nuclei. In addition, GLN stimulated a two-fold
increase of cellular 24-h 3H-thymidine incorporation above rates of
control cells bathed in standard media (p < 0.01); this effect was
also blocked by AO. GLN and phorbol 12-myristate 13-acetate (PMA)
stimulated ODC in a synergistic manner. The Na+/H+ exchange inhibitor
methyl isobutyl amiloride (MIA) blocked the enhancement of ODC by
GLN. GLN also induced the mRNA of the immediate-early gene c-jun. GLN
stimulates proliferation in a porcine jejunal cell line through a
mechanism requiring transamination and intact Na+/H+ exchange. This
stimulation of enterocyte proliferation by GLN suggests that
therapeutic GLN administration could facilitate epithelial recovery
in the injured small intestine.
Received 26 September 1994; accepted in final form 22 April 1995.
APS Manuscript Number G379-4.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 2 May 1995.