L-GLUTAMINE AND L-ASPARAGINE STIMULATE ODC ACTIVITY AND PROLIFERATIONIN A PORCINE JEJUNAL ENTEROCYTE LINE

We studied the effect of L-glutamine (Gln), the principal intestinal f uel, on proliferation of a porcine jejunal cell line, IPEC-J2. In cell s 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, me thyl-beta-D-glucoside, L-phenylalanine, ammonia, and aminoisobutyric a cid were ineffective. The alanine aminotransferase inhibitor aminooxya cetate (AO) inhibited the ODC stimulation by Gln in a dose-dependent m anner (half-maximal inhibitory concentration = 0.5 mM). AO was not tox ic to cells, as determined by propidium iodide uptake into nuclei. In addition, Gin stimulated a twofold increase of cellular 24-h [H-3]thym idine incorporation above rates of control cells bathed in standard me dia (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 thr ough a mechanism requiring transamination and intact Na+/H+ exchange. This stimulation of enterocyte proliferation by Gln suggests that ther apeutic Gln administration could facilitate epithelial recovery in the injured small intestine.