Growth hormone and epidermal growth factor upregulate specific sodium-dependent glutamine uptake systems in human intestinal C2BBe1 cells.
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, B(0,+), or ASC+B(0). A monolayer of C2(BBe)1 cells was exposed for 10 or 60 min to GH (500 microg/L), EGF (100 microg/L), both, or neither. Initial uptake of [(3)H]Gln (50 micromol/L) was measured in the presence of Na(+) or choline. The contributions of systems A, B(0,+), and ASC+B(0) were determined by competitive inhibition with arginine and/or alpha-(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, B(0,+), and ASC+B(0) 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 B(0+).
Ray
Edward C
EC
Department of Surgery, University of Rochester, School of Medicine and Dentistry, Rochester, NY 14642, USA.
Avissar
Nelly E
NE
Salloum
Rabih
R
Sax
Harry C
HC
D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005973:Glutamine / Q000378:metabolism*; D019382:Human Growth Hormone / Q000494:pharmacology*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007700:Kinetics; D012964:Sodium / Q000494:pharmacology
D005973:Glutamine; D019382:Human Growth Hormone; D004815:Epidermal Growth Factor; D012964:Sodium