Glutamine transport in isolated epithelial intestinal cells.: Identification of a Na+-dependent transport mechanism, highly specific for glutamine

L-Glutamine transport was evaluated in isolated cells from the guinea-pig small intestine by measuring [H-3]-L-glutamine uptake. Villous and crypt cells expressed Na+-dependent and Na+-independent transport mechanisms. Glutamine transport systems were identified using various amino acids and analogues as inhibitors. In both villous and crypt cells, 2-(methylamino)-isobutyrate (MeAIB), a system A inhibitor, did not inhibit Na+-dependent glutamine influx. 2-Aminobicyclo(2,2,1)heptane-2-carboxylate (BCH), a system B-0 and B-0,B-+ substrate, had no effect on Na+-dependent influx. Serine, cysteine and threonine, system ASC inhibitors, reduced Na+-dependent influx by 50%. Asparagine, but not histidine, system N inhibitors, reduced Na+-dependent glutamine influx by 50%, however the effect of asparagine was not additive to that of threonine. The remaining Na+-dependent glutamine influx (50%) was only inhibited by glutamine itself, by Na+ substitution (N-methyl-glucamine, K+, Li+) or by external pH reduction. Phenylacetyl-glutamine (PAG), a synthetic amino acid analogue, also inhibited this Na+-dependent, threonine-insensitive glutamine influx (IC50 2.45 mM). The Na+-independent uptake was partially inhibited by BCH, a system L inhibitor, and other neutral amino acids, but was not affect by PAG. Our results suggest that glutamine is transported in both villous and crypt cells by the Na+-independent system L, by the Na+-dependent system ASC and by an as yet undescribed Na+-dependent transport mechanism, highly specific for glutamine.