Growth hormone and epidermal growth factor upregulate specific sodium-dependent glutamine uptake systems in human intestinal C2BBe1 cells

Abstract

Glutamine (Gln) is one of the major oxidative fuels of the enterocyte and enters from the lumen via Na+-dependent transport mechanisms. When given parenterally, growth hormone (GH) + epidermal growth factor (EGF) increase apical Gln uptake after massive enterectomy in rabbits. Although both receptors are basolateral, GH and EGF are present in luminal contents. We hypothesized that short-term luminal growth factor exposure to enterocytes increases apical Gln uptake by selective upregulation of systems A, B0,+, or ASC+B0. A monolayer of C2BBe1 cells was exposed for 10 or 60 min to GH (500 μg/L), EGF (100 μg/L), both, or neither. Initial uptake of [3H]Gln (50 μmol/L) was measured in the presence of Na + or choline. The contributions of systems A, B0,+, and ASC+B0 were determined by competitive inhibition with arginine and/or α-(methylamino)butyric acid. Gln uptake was linear for up to 8 min. Na+-independent transport was negligible. Under control conditions the relative contributions of systems A, B0,+, and ASC+B0 were 0, 19 ± 6, and 80 ± 4%, respectively. GH alone had no effect on Gln transport. After 10 min of EGF exposure, Na+-dependent Gln uptake increased by 50% (P < 0.001) with no change in individual transport systems. Combined EGF and GH for 60 min increased Gln transport by system B 0,+ nearly 250% (P < 0.001) and system A from undetectable levels to 16% of total transport (P < 0.01). Thus, short-term luminal exposure to EGF+GH increases Na+-dependent Gln transport mainly by upregulating system B0+.