The early response of the jejunal brush border glutamine transporter to endotoxemia

Abstract

The early effects of endotoxin (4 hr after a single dose of Escherchia coli LPS, 7.5 mg/kg) on l-glutamine (GLN) transport across the jejunal brush border of rats were studied. Jejunal brush border membrane vesicles (BBMVs) were prepared by a Mg 2+ aggregation/differential centrifugation technique. Vesicle purity and integrity were confirmed by a 15-fold enrichment of brush border marker enzymes, osmotic activity, transport overshoots in the presence of sodium, and similar 1- and 2-hr equilibrium values. l-[ 3H]GLN transport in jejunal BBMVs was measured by a millipore filtration technique. Na +-dependent glutamine transport, which accounted for >80% of total transport, was increased twofold in BBMVs from endotoxin-treated rats (67 ± 5 pmole/mg protein/15 sec vs 38 ± 3, P < 0.01). Endotoxin treatment did not alter the activity of the Na +-independent carrier. Simultaneously, intestinal extraction of glutamine from the bloodstream fell by 56% (15.1 ± 2.3% in controls vs 6.6 ± 1.3% in endotoxin-treated rats, P < 0.01). This reduction in the uptake of circulating glutamine could not be accounted for by a fall in the arterial concentration. Thus, soon after endotoxemia brush border glutamine uptake is increased while consumption of glutamine across the basolateral membrane is decreased. This increased uptake may support protein synthesis and may provide a biochemical rationale for the use of early enteral nutrition after the onset of critical illness.