Original Article
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World J Gastroenterol. Mar 28, 2011; 17(12): 1569-1573
Published online Mar 28, 2011. doi: 10.3748/wjg.v17.i12.1569
Glutamate reduces experimental intestinal hyperpermeability and facilitates glutamine support of gut integrity
Mechteld AR Vermeulen, Jeffrey de Jong, Mathijs J Vaessen, Paul AM van Leeuwen, Alexander PJ Houdijk
Mechteld AR Vermeulen, Mathijs J Vaessen, Paul AM van Leeuwen, Department of Surgery, VU University Medical Center, 1007 MB Amsterdam, The Netherlands
Jeffrey de Jong, Department of Surgery, Gemini Hospital, 1782 GZ Den Helder, The Netherlands
Alexander PJ Houdijk, Department of Surgery, Medical Center Alkmaar, 1815 JD Alkmaar, The Netherlands
Author contributions: Vermeulen MAR and Vaessen MJ performed data analyses, interpreted the data and wrote the manuscript; de Jong J performed the experiments, designed the study, helped interpret data analyses and critically reviewed the manuscript; van Leeuwen PAM critically reviewed the manuscript and helped interpret the data; Houdijk APJ supervised all parts of the study and is responsible for all parts of the study; Vermeulen MAR and de Jong J contributed equally to this work.
Supported by VU University Medical Center, Amsterdam, The Netherlands
Correspondence to: Paul AM van Leeuwen, MD, Department of Surgery, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands. pam.vleeuwen@vumc.nl
Telephone: +31-20-4442908 Fax: +31-20-4443620
Received: April 9, 2010
Revised: February 7, 2011
Accepted: February 14, 2011
Published online: March 28, 2011
Abstract

AIM: 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.

CONCLUSION: 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.

Keywords: Apical; Basolateral; Flux; Glutamate; Glutamine; Gut protection; Gut wall integrity; Intestine; Permeability