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Biochemical and Molecular Actions of Nutrients

Growth Hormone and Epidermal Growth Factor Upregulate Specific Sodium-Dependent Glutamine Uptake Systems in Human Intestinal C2_BBe1 Cells^1,2

Department of Surgery, University of Rochester, School of Medicine and Dentistry, Rochester, NY 14642

⁴To whom correspondence should be addressed. E-mail: nelly_avissar{at}urmc.rochester.edu.

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+B⁰. A monolayer of C2_BBe1 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, B^0,+, and ASC+B⁰ were determined by competitive inhibition with arginine and/or -(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+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⁺.

KEY WORDS: • enterocytes • amino acid transport systems A, ASC, B⁰, B^0,+ • glutamine • epidermal growth factor • growth hormone

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				Q. Huang, N. Li, W. Zhu, Q. Li, and J. Li Glutamine Transporter ASCT2 Was Down-Regulated in Ischemic Injured Human Intestinal Epithelial Cells and Reversed by Epidermal Growth Factor JPEN J Parenter Enteral Nutr, March 1, 2007; 31(2): 86 - 93. [Abstract] [Full Text] [PDF]

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