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Am J Physiol Gastrointest Liver Physiol 269: G591-G599, 1995;
0193-1857/95 $5.00
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AJP - Gastrointestinal and Liver Physiology, Vol 269, Issue 4 591-G599, Copyright © 1995 by American Physiological Society


ARTICLES

L-glutamine and L-asparagine stimulate ODC activity and proliferation in a porcine jejunal enterocyte line

H. M. Kandil, R. A. Argenzio, W. Chen, H. M. Berschneider, A. D. Stiles, J. K. Westwick, R. A. Rippe, D. A. Brenner and J. M. Rhoads
Department of Pediatrics, University of North Carolina, Chapel Hill 27599-7220, USA.

We studied the effect of L-glutamine (Gln), the principal intestinal fuel, on proliferation of a porcine jejunal cell line, IPEC-J2. In cells synchronized by serum deprivation for 4 h, Gln stimulated ornithine decarboxylase (ODC; EC 4.1.1.17) 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 isosmolar mannitol, glucose, methyl-beta-D-glucoside, L-phenylalanine, ammonia, and aminoisobutyric acid were ineffective. The alanine aminotransferase inhibitor aminooxyacetate (AO) inhibited the ODC stimulation by Gln in a dose-dependent manner (half-maximal inhibitory concentration = 0.5 mM). AO was not toxic to cells, as determined by propidium iodide uptake into nuclei. In addition, Gln stimulated a twofold 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 stimulated ODC in a synergistic manner. The Na+/H+ exchange inhibitor methylisobutyl amiloride 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.


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