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Original communication| Volume 113, ISSUE 5, P552-559, May 1993

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Regulation of small intestinal glutamine transport by epidermal growth factor

  • Rabih M. Salloum
    Affiliations
    From the Departments of Surgery, Biochemistry/Molecular Biology, Physiology, and Obstetrics and Gynecology, university of Florida College of Medicine, Gainesville, Fla., USA
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  • Bruce R. Stevens
    Footnotes
    Affiliations
    From the Departments of Surgery, Biochemistry/Molecular Biology, Physiology, and Obstetrics and Gynecology, university of Florida College of Medicine, Gainesville, Fla., USA
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  • Gregory S. Schultz
    Footnotes
    Affiliations
    From the Departments of Surgery, Biochemistry/Molecular Biology, Physiology, and Obstetrics and Gynecology, university of Florida College of Medicine, Gainesville, Fla., USA
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  • Wiley W. Souba
    Correspondence
    Reprint requests: Wiley W. Souba, MD, ScD, Department of Surgery, Box J-286, JHMHSC, Gainesville, FL 32610.
    Footnotes
    Affiliations
    From the Departments of Surgery, Biochemistry/Molecular Biology, Physiology, and Obstetrics and Gynecology, university of Florida College of Medicine, Gainesville, Fla., USA
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  • Author Footnotes
    a Supported by National Institutes of Health grant DK 38915.
    b Supported by National Institutes of Health grant EY 05587.
    c Supported by National Institutes of Health grants CA 45327 and HL 44986, a grant from the Veterans Administration Merit Review Board, and a Career Development Award from the American Cancer Society.
DOI:https://doi.org/10.5555/uri:pii:003960609390118W
Regulation of small intestinal glutamine transport by epidermal growth factor
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      Abstract

      Background. Epidermal growth factor (EGF) stimulates cell replication and increases DNA content of the small intestine, but its effects on mucosal amino acid transport are unknown.
      Methods. To investigate these effects, we treated adult rats with vehicle or EGF (10 μg/100 gm body weight subcutaneously every 8 hours for three doses). Jejunal brush border membrane vesicles (BBMVs) from each group were prepared by Mg++ aggregation/differential centrifugation. BBMVs were enriched fifteenfold in alkaline phosphatase, indicating BBMV purity. Transport of 3H-glutamine and 3H-alanine was studied by a rapid mixing filtration technique. Uptakes were primarily Na+ dependent, occurred in an osmotically active space, exhibited classic overshoots, and had similar 2-hour equilibrium values.
      Results. Glutamine transport by BBMVs more than doubled in rats treated with EGF (16.4 ± 0.1 pmol glutamine/mg protein/10 sec in EGF vs 7.1 ± 0.5 pmol glutamine/mg protein/10 sec in controls; p < 0.001). Kinetic studies of the glutamine transporter showed that the increase in transport was the result of a 70% increase in maximal transport velocity (total maximum glutamine uptake = 193 ± 8 pmol glutamine/mg protein/10 sec in EGF vs 114 ± 7 pmol glutamine/mg protein/10 sec in controls; p < 0.0001 with no change in transporter affinity (transporter affinity = 224 ± 6 μmol/L in EGF vs 242 ± 37 μmol/L in controls; difference, not significant). Alanine uptake by BBMVs was also increased with EGF administration (10.2 ± 2.0 pmol alanine/mg protein/10 sec in EGF vs 4.5 ± 0.5 pmol alanine/mg protein/10 sec in controls; p < 0.005). Simultaneously, glucose transport was decreased by 50% in EGF-treated rats, indicating that the Na+-dependent glucose cotransporter is regulated independently from and opposite to ammo acid transporters.
      Conclusions. We conclude that EGF up-regulates amino acid transport activity in jejunal BBMVs, an event that is most likely caused by an increase in de novo biosynthesis of transporter protein. The increase in amino acid uptake not only may support de novo protein synthesis but, in the case of glutamine, also may be required for energy production and nucleotide biosynthesis.
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      References

        • Gospodarowicz D
        Epidermal and nerve growth factors in mammalian development.
        Annu Rev Physiol. 1981; 43: 251-263
        • Chabot JG
        • Payet N
        • Hugon JS
        Effects of epidermal growth factor (EGF) on adult mouse small intestine in vivo and in organ tissue culture.
        Comp Biochem Physiol [A]. 1983; 74: 247-252
        • Bans-Schlegel SP
        • Quintero J
        Human esophageal carcinoma cells have fewer but higher affinity epidermal growth factor receptors.
        J Biol Chem. 1986; 261: 4359-4362
        • Richman RA
        • Claus TH
        • Plikis SJ
        • et al.
        Hormonal stimulation of DNA synthesis in primary cultures of adult rat hepatocytes.
        in: 1st ed. Proc Natl Acad Sci USA. 73. 1976: 3589-3593
        • Cohen S
        Isolation of a mouse submaxillary gland protein accelerating incisor eruption and eyelid opening in the newborn animal.
        J Biol Chem. 1962; 237: 1555-1562
        • Savage RC
        • Cohen S
        Epidermal growth factor: chemical and biological characterization.
        Recent Prog Horm Res. 1974; 30: 533-550
        • Skov-Olsen P
        • Nexo E
        Quantitation of epidermal growth factor in the rat: identification and partial characterization of duodenal EGF.
        Scand J Gastroenterol. 1983; 18: 771-776
        • Ulshen MH
        • Lyn-Cook LE
        • Raash RH
        Effects of intraluminal epidermal growth factor on mucosal proliferation in the small intestine of adult rats.
        Gastroenterology. 1986; 91: 1134-1140
        • Hiramatsu Y
        • Eguchi K
        • Sekiba K
        Hormonal regulation of ornithine decarboxylase and polyamines in primary cultured rat hepatocytes: differences in hormonal response between adult and fetal hepatocytes.
        Acta Med Okayama. 1985; 39: 275-287
        • Taylor JM
        • Mitchell WM
        • Cohen S
        Characterization of the high molecular weight form of epidermal growth factor.
        J Biol Chem. 1974; 249: 3198-3203
        • Yeh YC
        • Scheving LA
        • Tsai TH
        • et al.
        Circadian stage-dependent effects of epidermal growth factor on deoxyribonucleic acid synthesis in ten different organs of the adult male mouse.
        Endocrinology. 1981; 109: 644-651
        • Fehlman EJ
        • Anres D
        • Grossman MI
        Epidermal growth factor stimulates ornithine decarboxylase activity in the digestive tract of mouse (40357).
        in: 1st ed. Proc Soc Exp Biol Med. 159. 1978: 400-402
        • Skov-Olsen P
        • Poulsen SS
        • Kirkegaard P
        • et al.
        Role of submandibular saliva and epidermal growth factor in gastric cytoprotection.
        Gastroenterology. 1984; 87: 103-108
        • Sakamoto T
        • Swierczek JS
        • Ogden WD
        • et al.
        Cytoprotective effect of pentagastrin and epidermal growth factor on stress ulcer formation: possible role of somatostatin.
        Ann Surg. 1985; 201: 290-295
        • Jacobs DO
        • Evans DA
        • Mealy K
        • et al.
        Combined effects of glutamine and epidermal growth factor on the rat intestine.
        Surgery. 1988; 104: 358-364
        • Windmueller HG
        Glutamine utilization by the small intestine.
        Adv Enzymol. 1982; 53: 201-237
        • Souba WW
        • Smith RJ
        • Wilmore DW
        Glutamine metabolism by the intestinal tract.
        JPEN. 1985; 9: 608-617
        • Souba WW
        • Klimberg VS
        • Plumley DA
        • et al.
        The role of glutamine in maintaining a healthy gut and supporting the metabolic response to injury and infection.
        J Surg Res. 1990; 48: 383-391
        • Stevens BR
        • Kaunitz J
        • Wright EM
        Intestinal transport of amino acids and sugars: advances using membrane vesicles.
        Annu Rev Physiol. 1984; 46: 417-433
        • Stevens BR
        • Ross HJ
        • Wright EM
        Multiple transport pathways for neutral amino acids in rabbit jejunal brush border border vesicles.
        J Membr Biol. 1982; 66: 213-225
        • Mircheff AK
        • Wright EM
        Analytical isolation of plasma membranes of intestinal epithelial cells: identification of Na, K-ATPase rich membranes and the distribution of enzyme activities.
        J Membr Biol. 1976; 28: 309-333
        • Stevens BR
        • Wright EM
        Kinetics of the intestinal brush border proline (imino) carrier.
        J Biol Chem. 1987; 262: 6546-6551
        • Hollenberg MD
        • Cuatrecasas P
        Insulin and epidermal growth factor: human fibroblast receptors related to deoxyribonucleic acid synthesis and amino acid uptake.
        J Biol Chem. 1975; 250: 3845-3853
        • Marti U
        • Burwen SJ
        • Jones AL
        Biological effects of epidermal growth factor, with emphasis on the gastrointestinal tract and liver: an update.
        Hepatology. 1989; 9: 126-138
        • Stevens BR
        Amino acid transport in intestine.
        in: Haussinger D Kilberg M Mammalian amino acid transport: mechanisms and control. Plenum, New York1992
        • Pan M
        • Nue J
        • Stevens BR
        Regulation of amino acids transport in differentiating intestinal epithelial cells in culture (Caco-2) [Abstract].
        FASEB J. 1991; 5: A760
        • Blais A
        • Bissonnette P
        • Bertelot A
        Common characteristics for Na+-dependent sugar transport in Caco-2 cells and human fetal colon.
        J Membrane Biol. 1987; 99: 113-125

      28. Souba WW, Pan M, Stevens BR. Kinetics of glutamine transport in confluent Caco-2 cell monolayers. Biochem Biophys Res Commun (in press).

        • Shotwell MA
        • Kilberg MS
        • Oxender DL
        The regulation of neutral amino acid transport in mammalian cells.
        Biochim Biophys Acta. 1970; 727: 283-295
        • Ferraris RP
        • Diamond JM
        Specific regulation of intestinal nutrient transporters by their dietary substrates.
        Annu Rev Physiol. 1989; 51: 125-141
        • Diamond JM
        • Karasov WH
        Adaptive regulation of intestinal nutrient transporters.
        in: 1st ed. Proc Natl Acad Sci USA. 84. 1987: 2242-2245
        • Bulus NM
        • Abumrad NN
        • Ghishan FK
        • et al.
        Characteristics of glutamine transport in dog jejunal brush border membrane vesicles.
        Am J Physiol. 1989; 257: G80-G85
        • Carpenter G
        • Cohen S
        Epidermal growth factor.
        Annu Rev Biochem. 1979; 48: 193-216
        • Visciano G
        • Fehlmann M
        Mechanism of the inhibitory effect of EGF on cAMP-stimulated amino acid transport.
        Mol Cell Endocrinol. 1984; 37: 103-107
        • Salloum RM
        • Souba WW
        • Fernandez A
        • et al.
        Dietary modulation of small intestinal glutamine transport in intestinal brush border membrane vesicles of rats.
        J Surg Res. 1990; 48: 635-638

      Article info

      Publication history

      Accepted: January 6, 1992

      Identification

      DOI: https://doi.org/10.5555/uri:pii:003960609390118W

      Copyright

      © 1993 Published by Elsevier Inc.

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