title: Glutamate reduces experimental intestinal hyperpermeability and facilitates glutamine support of gut integrity.
abstract: OBJECTIVE
  To assess whether glutamate plays a similar role to glutamine in preserving gut wall integrity.
  
  
  METHODS
  The effects of glutamine and glutamate on induced hyperpermeability in intestinal cell lines were studied. Paracellular hyperpermeability was induced in Caco2.BBE and HT-29CL.19A cell lines by adding phorbol-12,13-dibutyrate (PDB) apically, after which the effects of glutamine and glutamate on horseradish peroxidase (HRP) diffusion were studied. An inhibitor of glutamate transport (L-trans-pyrrolidine-2,4-dicarboxylic acid: trans-PDC) and an irreversible blocker (acivicin) of the extracellular glutamine to glutamate converting enzyme, γ-glutamyltransferase, were used.
  
  
  RESULTS
  Apical to basolateral HRP flux increased significantly compared to controls not exposed to PDB (n = 30, P < 0.001). Glutamine application reduced hyperpermeability by 19% and 39% in the respective cell lines. Glutamate application reduced hyperpermeability by 30% and 20%, respectively. Incubation of HT29CL.19A cells with acivicin and subsequent PDB and glutamine addition increased permeability levels. Incubation of Caco2.BBE cells with trans-PDC followed by PDB and glutamate addition also resulted in high permeability levels.
  
  
  CONCLUSIONS
  Apical glutamate -similar to glutamine- can decrease induced paracellular hyperpermeability. Extracellular conversion of glutamine to glutamate and subsequent uptake of glutamate could be a pivotal step in the mechanism underlying the protective effect of glutamine.
authors.affiliation: Department of Surgery, VU University Medical Center, 1007 MB Amsterdam, The Netherlands.
authors.forename: Mechteld A R
authors.initials: MA
authors.lastname: Vermeulen
authors.forename: Jeffrey
authors.initials: J
authors.lastname: de Jong
authors.forename: Mathijs J
authors.initials: MJ
authors.lastname: Vaessen
authors.forename: Paul Am
authors.initials: PA
authors.lastname: van Leeuwen
authors.forename: Alexander P J
authors.initials: AP
authors.lastname: Houdijk
mesh_terms: D000704:Analysis of Variance; D018938:Caco-2 Cells; D003998:Dicarboxylic Acids / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D050491:Glutamate Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006801:Humans; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D007555:Isoxazoles / Q000494:pharmacology; D010539:Permeability; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D005723:gamma-Glutamyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D003998:Dicarboxylic Acids; D004791:Enzyme Inhibitors; D050491:Glutamate Plasma Membrane Transport Proteins; D007555:Isoxazoles; D011759:Pyrrolidines; D005973:Glutamine; D015240:Phorbol 12,13-Dibutyrate; D018698:Glutamic Acid; C083486:pyrrolidine-2,4-dicarboxylic acid; D005723:gamma-Glutamyltransferase; C006303:acivicin