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PubMed2002

Transepithelial transport of prodrugs of the HIV protease inhibitors saquinavir, indinavir, and nelfinavir across Caco-2 cell monolayers.

PURPOSE: [corrected] This study is dedicated to the permeation of various amino acid-, D-glucose-, and PEG-conjugates of indinavir, saquinavir, and nelfinavir across monolayers of Caco-2 cells as models of the intestinal barrier. This screening is aimed at detecting the most promising prodrugs for improving the intestinal absorption of these protease inhibitors. METHODS: The bidirectional transport of the prodrugs was investigated using P-gp-expressing Caco-2 monolayers grown on membrane inserts using high-performance liquid chromatography for quantitation. RESULTS: The L-valyl, L-leucyl, and L-phenylalanyl ester conjugates led to an enhancement of the absorptive flux of indinavir or saquinavir. These results are likely attributable to an active transport mechanism and/or to a decrease of their efflux by carriers such as P-gp. Connection of tyrosine through its hydroxyl, of D-glucose, or of polyethylene glycol decreased their absorptive and secretory diffusion. CONCLUSIONS: Conjugation of the protease inhibitors to amino acids constitutes a most appealing alternative that could improve their intestinal absorption and oral bioavailability. Whether it could improve their delivery into the central nervous system remains to be explored. D-Glucose conjugation will most probably not improve their intestinal absorption or their crossing of the blood-brain barrier. If some pharmacologic benefits are to be expected from PEG-protease inhibitor conjugates, they must then be administered intravenously.

Biological Transport↗
PubMed2005

A murine model of ulcerative colitis: induced with sinusitis-derived superantigen and food allergen.

BACKGROUND: The etiology of ulcerative colitis (UC) is to be understood. The basic pathological feature of UC is intestinal chronic inflammation. Superantigen, such as Staphylococcus enterotoxin B (SEB), is reported to compromise intestinal barrier function by increasing epithelial permeability and initiate inflammation in the intestinal mucosa. Inasmuch as anatomic position of the sinus, chronic sinusitis-derived SEB may follow the secretion and to be swallowed down to the gastrointestinal tract and induce lesions to the intestinal mucosa. METHODS: Sinus wash fluid (SWF, containing SEB) was collected from a group of patients with both chronic sinusitis (CS) and UC. A group of mice were sensitized to ovalbumin (OVA) in the presence of SWF. The sensitized mice were challenged with the specific antigen OVA. The inflammatory status of the colonic tissue was determined with histology, serology and electron microscopy. Using horseradish peroxidase (HRP) as a tracer, another group of mice was stimulated with SWF for 2 hours. The HRP activity was detected in the colonic tissue with enzymatic approaches and electron microscopy. RESULTS: Epithelial hyperpermeability in colonic epithelium was induced by stimulating with SWF. The HRP activity in the colonic mucosa was almost 11 times more in the SWF treated group (3.2 +/- 0.6 microg/g tissue) than the control group (0.3 +/- 0.1 microg/g tissue). Mice were sensitized using a mixture of SWF and OVA (serum OVA-specific IgE was detected with a highest titer as 1:64). Challenge with OVA induced extensive inflammation in the colonic mucosa by showing (1) marked degranulation in mast cells (MC, 46.3 +/- 4.5%) and eosinophils (Eo, 55.7 +/- 4.2%); (2) inflammatory cell infiltration (MC = 145.2 +/- 11.4; Eo = 215.8 +/- 12.5; mononuclear cell = 258.4 +/- 15.3/mm2 tissue); (3) increased MPO activity (12.9 +/- 3.2 U/g tissue) and inflammatory scores (1.8 +/- 0.3); (4) mucosal surface ulcers; (5) edema in the lamina propria; (6) bacterial translocation and abscess formation in the subepithelial region. CONCLUSION: Introducing Sinusitis-derived SEB-containing SWF to the gastrointestinal tract compromised colonic mucosal barrier function increasing epithelial permeability to luminal macromolecular protein in mice. The SWF facilitated colonic mucosal sensitization to luminal antigen. Multiple challenging the sensitized colonic mucosa with specific antigen OVA induced inflammation, induced a condition similar to human ulcerative colitis.

Adult↗
PubMed2006

Small-bowel permeability in collagenous colitis.

OBJECTIVE: Collagenous colitis (CC) is a chronic inflammatory bowel disease that affects the colon. However, some patients with CC present with accompanying pathologic small-bowel manifestations such as coeliac disease, defects in bile acid absorption and histopathologic changes in small-intestinal biopsies, indicating that CC is a pan-intestinal disease. In small-intestinal disease, the intestinal barrier function may be impaired, and the permeability of the small intestine altered. The purpose of this research was to study small-bowel function in patients with CC as expressed by intestinal permeability. MATERIAL AND METHODS: Ten patients with CC and chronic diarrhoea participated in the study. Coeliac disease was excluded by small-bowel biopsy and/or serology. Intestinal permeability was assessed as urinary excretion (ratios) 2, 4 and 6 h after ingestion of 14C-labelled mannitol (14C-mannitol) and 99mTc-labelled diethylenetriamine-pentaacetic acid (99mTc-DTPA). Data were compared with the results from healthy controls. RESULTS: No difference was found between groups in urinary excretion of 14C-mannitol and 99mTc-DTPA after 2, 4 or 6 h, respectively. Likewise, no significant differences in the 99mTc-DTPA/14C-mannitol ratios between patients and controls were detected after 2 h: 0.030 (0.008-0.130) versus 0.020 (0.007-0.030), p = 0.19, after 4 h: 0.040 (0.009-0.180) versus 0.020 (0.008-0.040), p = 0.14 or after 6 h: 0.040 (0.012-0.180) versus 0.020 (0.010-0.040), p = 0.17. CONCLUSIONS: No alterations in intestinal permeability in patients with CC could be demonstrated. Impairment of the integrity of the mucosa of the small bowel and the presence of a general dysfunction of the small intestine in patients with CC seem unlikely.

Adult↗
PubMed1998

Derangement of mucosal barrier function by bacteria colonizing the rat colonic mucosa.

BACKGROUND: Interaction between gut flora and the intestinal barrier may involve changes in permeability. METHODS: Rats with a colonic segment excluded from faecal transit were surgically prepared. Matched groups were either kept on luminal antibiotics to prevent colonization of the segment or recolonized with mixed rat flora. Permeability to low-dose trinitrobenzenesulphonic acid (TNBS) or trinitrophenol (TNP), and mucosal injury by the compounds at a high dose were tested in antibiotic and recolonized rats (the compounds differ in water solubility but share a common antigenic domain). RESULTS: Lumen to blood clearance of the hydrophilic probe (TNBS) was faster in recolonized than in antibiotic rats. The hydrophobic compound TNP was absorbed at faster rates than TNBS, but there was no difference between antibiotic and recolonized rats. Instillation of TNBS at a high dose induced mucosal release of inflammatory mediators and tissue myeloperoxidase accumulation in recolonized rats but not in antibiotic rats. Large necrotic lesions with submucosal involvement after TNBS were only observed in recolonized rats. In contrast, TNP induced mucosal inflammation and large lesions with submucosal necrosis both in recolonized and in antibiotic rats. CONCLUSION: Colonizing bacteria may increase intestinal permeability to hydrophilic compounds and render the mucosa susceptible to injury.

Animals↗
PubMed1998

[Dietary fiber protects intestinal structure and barrier function].

OBJECTIVE: To evaluate the effect of dietary fiber on intestinal structure and barrier function of 5-fluorouracil (5-Fu) challenged rat. METHOD: Thirty Wistar rats were divided randomly into three groups (10 each group): Chow, enteric nutrition (EN), and EN + Fiber group. Both EN and EN + Fiber group were isonitrogenic and isocaloric. The rats kept their diet respectively for 8 days. 5-Fu was injected intraperitoneally on day 4 postoperatively. Intestinal permeability (L/M) was measured respectively on day 3 and day 7. On day 8, the bacterial translation, wet weight and mucous thickness of both small intestine and colon and the villus height of small intestine were measured. The rats were weighted before and after experiment respectively. RESULT: The body weight loss of the EN + Fiber group (-3.1 +/- 3.4 g) was less than that of the EN group (-6.6 +/- 5.2 g) (P < 0.05), whereas the Chow group gained body weight (4.9 +/- 4.3 g) (P < 0.01 when compared with EN and EN + Fiber group). The parameters of intestinal structures of the EN + Fiber group was superior to the EN group (P < 0.05). The L/M of both EN + Fiber (from 0.0265 +/- 0.0073 to 0.0274 +/- 0.0068) and the Chow group (from 0.0268 +/- 0.0039 to 0.0281 +/- 0.0044) was unchanged (P > 0.05 for both) after 5-Fu challenged, whereas that of the EN group increased (from 0.0289 +/- 0.0070 to 0.0331 +/- 0.0084) (P < 0.01). The incidence of bacterial translocation to MLN of both EN + Fiber group and the Chow group (20%) was lower than that of the EN group (70%) (P < 0.05). CONCLUSION: The dietary fiber protects the intestinal structure and barrier function of 5-Fu challenged rats.

Animals↗
PubMed2006

Colon submucosal microdialysis: a novel in vivo approach in barrier function assessment - a pilot study in rats.

During shock, prognosis of a patient depends largely on intestinal barrier function. The potency of gut epithelium to represent an obstacle to toxins is determined by the blood supply. All established methods of mucosal function determination necessitate the functional involvement of bloodstream. Microdialysis allows monitoring of extracellular substances in the gut submucosa, but its potential use for gut barrier integrity assessment is unknown. Twelve rats underwent perfusion of the descending colon either with 20 % ethanol or control medium (vehicle). Both media contained equal amounts of a radioactive tracer substance ((51)Cr-EDTA). Mucosal permeability for (51)Cr-EDTA was assessed by microdialysate to luminal perfusate activity ratios. Sampling was performed using the colon submucosal microdialysis technique. The group subjected to ethanol treatment had profound macro- and microscopical alterations in perfused colonic segment associated with a significant increase in tracer permeability during ethanol exposure (2.354+/-0.298 % for ethanol as opposed to 0.209+/-0.102 % for control group, p 0.01), which remained elevated for 60 min after cessation of ethanol administration (3.352+/-0.188 % for ethanol compared to 0.140+/-0.0838 % for the control group, p 0.001). Submucosal microdialysis with radioactive tracer substance can be considered a feasible and advantageous alternative of gut barrier function estimation. Parallel monitoring of local tissue chemistry with this method remains a challenge in the future.

Animals↗
PubMed2000

Phagocytic and intestinal endothelial and epithelial barrier function during the early stage of small intestinal ischemia and reperfusion injury.

The effects of intestinal ischemia and reperfusion (I/R) on small intestinal mucosal endothelial and epithelial barrier integrity and phagocytic function were assessed in rats subjected to 20- or 40-min mesenteric ischemia and a 3-h reperfusion. The results showed that human serum albumin (125I-HSA) flux through the endothelial layer to the interstitial space increased as did 125I-HSA clearance from blood to the gut lumen and 131I-HSA flux from the gut lumen to the interstitial space in rats with I/R. E. coli adhering to microvilli, invading and passing into the microvessels, were noted on the small intestinal mucosa in animals subjected to 40-min ischemia and a 3-h reperfusion. Phagocytic function increased, especially in the small intestinal wall, lungs, liver, and spleen in the groups with I/R, correlating with the length of ischemia. The results imply that both endothelial and epithelial barrier integrity is impaired in the early phase after I/R and that the epithelial barrier more effectively restricts macromolecular leakage compared with the endothelial barrier. I/R impairs the intestinal barrier not only by causing tissue hypoxia but also by activating the phagocytic system and aggravating barrier damage, which finally may result in bacterial translocation and remote organ dysfunction.

Animals↗
PubMed2005

Differential expression of claudin-2 along the human intestine: Implication of GATA-4 in the maintenance of claudin-2 in differentiating cells.

Claudins, and particularly claudin-2, are important regulatory components of tight junction permeability. A better understanding of the involvement of claudin-2 in intestinal barrier functions requires the characterization of its distribution and regulation in the intestine. Interestingly, the claudin-2 gene promoter harbors a number of similarities to that of sucrase-isomaltase, a marker of enterocyte differentiation. We thus investigated the expression of claudin-2 in relation to the transcription factors CDX2, HNF-1alpha, and GATA-4 in the human intestine. The characterization of claudin-2 and the expression of the above transcription factors were performed by immunofluorescence, Western blot, and RT-PCR in the developing human intestinal epithelium. The functional role of CDX2, HNF-1alpha, and GATA-4 on claudin-2 regulation was also examined by ectopic expression studies in intestinal cell models. Claudin-2 was detected in both crypt and villus cells of the small intestine but restricted to undifferentiated crypt cells in the colon. CDX2 and HNF-1alpha were expressed along the entire intestine whereas GATA-4 was undetectable in the colon. Accordingly, in the colonic Caco-2 cell model, claudin-2 was found to be present only in undifferentiated cells. Like in the colonic epithelium, GATA-4 was found to be also lacking in Caco-2 cells while CDX2 and HNF-1alpha were present at significant levels. Cotransfection experiments showed that the claudin-2 promoter was activated by CDX2, HNF-1alpha, and GATA-4 in a cooperative manner. Furthermore, forced GATA-4 expression in Caco-2 cells enhances maintenance of claudin-2 expression during differentiation. These observations suggest that optimal claudin-2 expression in the gut relies on the presence of GATA-4, suggesting a role for this factor in intestinal regionalization.

CDX2 Transcription Factor↗
PubMed2006

IgG transport across mucosal barriers by neonatal Fc receptor for IgG and mucosal immunity.

Mucosal secretions of the human gastrointestinal, respiratory, and genital tracts contain significant quantities of IgG. The neonatal Fc receptor for IgG (FcRn) plays a major role in regulating host IgG levels and transporting IgG and associated antigens across polarized epithelial barriers. The FcRn can then recycle the IgG/antigen complex back across the intestinal barrier into the lamina propria for processing by dendritic cells and presentation to CD4(+) T cells in regional organized lymphoid structures. FcRn, through its ability to secrete and absorb IgG, thus integrates luminal antigen encounters with systemic immune compartments and, as such, provides essential host defense and immunoregulatory functions at the mucosal surfaces.

Antigens↗
PubMed2006

Concurrent exposure to thermal stress and oral Ag induces intestinal sensitization in the mouse by a mechanism of regulation of IL-12 expression.

The mechanism of food allergy remains unclear. The absorption of intact protein Ag into the intestinal tissue is a prerequisite in the development of intestinal sensitization. Previous studies indicate that thermal stress compromises the intestinal barrier function. Mice were concurrently exposed to thermal stress and oral Ag. Intestinal sensitivity, levels of serum-specific IgE, IL-4 and INF-gamma were assessed. Intestinal dendritic cell, Th1 and Th2 functions were determined. The mice that were treated with thermal stress and oral Ag showed high levels of serum Ag-specific IgE, intestinal mast cell activation in response to oral Ag challenge, suppression of IL-12 expression in the intestinal dendritic cells, inhibition of T-bet expression and Th1 function and marked increases in (GATA)3 expression and Th2 function. Mice exposed to thermal stress alone or oral Ag alone did not show any signs of the intestinal sensitization. Pretreatment with IL-12 inhibited the intestinal sensitization induced by the concurrent exposure to thermal stress and Ag gavage. We conclude that although Ag absorption is essential, Ag absorption alone is insufficient; other accessory factors that can disturb the local immune homeostasis are also required for the induction of intestinal sensitization. The present study illustrates that concurrent exposure to thermal stress and oral Ag can prove to be a factor in the induction of intestinal sensitization by a mechanism of regulating IL-12 expression.

Administration, Oral↗
PubMed1998

[Lack of effect of EGF on epithelial barrier function in experimental TNBS colitis].

This study tested the hypothesis that EGF has a protective effect on the intestinal barrier function in experimental TNBS-induced colitis. EGF was given intraperitoneally one hour before and 24 hours after induction of colitis. The rats were killed 48 hours after induction of colitis: The distal colon was resected and mounted into Ussing chambers. Flux measurements were performed for Na+ and mannitol, and epithelial and subepithelial resistances were determined. A semiquantitative histological score was used to grade acute and chronic inflammation. Compared to controls, TNBS caused a 3-fold increase in both fluxy, indicating enhanced paracellular permeability. There rates was a severe reduction of total and epithelial resistances indicating a dramatic defect of epithelial barrier function. EGF failed to improve the electrophysiologic and histologic parameters. Therefore, EFG has no protective effective in experimental TNBS colitis.

Animals↗
PubMed1994

Effect of critical illness on microbial translocation and gastrointestinal mucosa permeability.

It has been hypothesized that the barrier function of the gastrointestinal tract is deranged in patients with trauma, sepsis, or other critical illnesses. Derangements in intestinal barrier function might lead to bloodstream invasion by gut-derived microbes and/or activation of inflammatory cells in the submucosa of the intestine or within the liver. Activated immune cells are capable of releasing a number of inflammatory mediators, including eicosanoids and cytokines, which have been implicated in the pathogenesis of the multiple organ dysfunction syndrome (MODS). Thus, gut-barrier dysfunction might be primary factor leading to MODS in patients with critical illness. Two distinct forms of gut-barrier dysfunction have been described. The first, called translocation, appears to a transcellular process, whereby particulate antigens, including viable microbes, are transported across enterocytes into the submucosal compartment. The second is an increase in the paracellular permeability of the intestinal epithelium, which permits increased transmucosal absorption of water-soluble macromolecules. Pathological increases in both translocation and permeability occur in a number of animal models of critical illness. Moreover, a number of studies have documented that intestinal permeability is increased in humans with trauma, sepsis, burns, or other serious, acute medical problems. Nevertheless, convincing data to establish a causal link between gut-barrier dysfunction and organ failure in humans are lacking, and the importance of translocation and/or mucosal hyperpermeability on the development of MODS in patients remains to be elucidated.

Bacterial Physiological Phenomena↗
PubMed1997

Intestinal inflammation and barrier function in HLA-B27/beta 2-microglobulin transgenic rats.

BACKGROUND: Since intestinal inflammation is correlated with impaired barrier functions, transgenic HLA-B27/human beta 2-microglobulin rats that spontaneously develop intestinal inflammation were used to investigate whether onset of inflammation or impaired barrier function was the initial event. METHODS: During the age period of 9-14 weeks, transgenic and non-transgenic (control) rats were gavaged weekly with the marker molecules, 51Cr-ethylenediaminetetraacetic acid, 1-deamino-8-D-arginine vasopressin, and albumin, which were quantified in blood or urine. RESULTS: At 12 weeks of age the first signs of inflammation appeared with decreased body weight gain, decreased urine production, and onset of diarrhea. By 14-15 weeks of age all transgenic rats had developed intestinal inflammation, as confirmed by histology and increased myeloperoxidase content, whereas no inflammation was observed in controls. Intestinal passage of the markers did, however, not differ between transgenic and control rats over the studied period. CONCLUSIONS: The results suggest that intestinal inflammation precedes altered intestinal barrier function in this inflammation model.

Animals↗
PubMed2006

Thoracic epidural analgesia augments ileal mucosal capillary perfusion and improves survival in severe acute pancreatitis in rats.

BACKGROUND: Acute pancreatitis has been linked to intestinal barrier dysfunction and systemic inflammatory response with high mortality. Thoracic epidural analgesia improves intestinal perfusion. The authors hypothesized that thoracic epidural analgesia influences microcirculation injury, inflammatory response, and outcome of acute pancreatitis in rats. METHODS: Control groups underwent a sham procedure or untreated pancreatitis induced by intraductal taurocholate injection. In the treatment groups, epidural analgesia was commenced immediately or after a 7-h delay. Fifteen hours after injury, the ileal mucosal perfusion was assessed by intravital microscopy. Thereby, the intercapillary area between all perfused capillaries and between continuously perfused capillaries only was used to differentially quantify total and continuous capillary mucosal perfusion. Villus blood flow and serum levels of amylase, lactate, and interleukin 6 were determined, and pancreatic injury was scored histologically. Seven-day survival was recorded in an additional 30 rats undergoing untreated pancreatitis or pancreatitis with epidural analgesia. RESULTS: In untreated pancreatitis, decreased total capillary perfusion increased the total intercapillary area by 24%. Furthermore, loss of continuous perfusion increased continuous intercapillary area to 228%. After immediate and delayed epidural analgesia, continuous perfusion was restored (P < 0.05). Blood flow decreased 50% in untreated pancreatitis but was preserved by epidural analgesia (P < 0.05). Biochemical and histologic signs of pancreatitis were not affected by epidural analgesia. Lactate and interleukin-6 levels increased in untreated pancreatitis, which was prevented in the treatment groups (P < 0.05). Epidural analgesia increased 7-day survival from 33% to 73% (P < 0.05). CONCLUSION: Thoracic epidural analgesia attenuated systemic response and improved survival in severe acute pancreatitis. These effects might be explained by improved mucosal perfusion.

Analgesia, Epidural↗
PubMed2006

Effects of crude red kidney bean lectin (phytohemagglutinin) exposure on performance, health, feeding behavior, and gut maturation of pigs at weaning.

The aim of this study was to obtain information that could help to ease the weaning transition in commercial pig production. Before weaning, phytohemagglutinin (PHA) in the form of a crude preparation of red kidney bean lectin was fed by gavage to 24 crossbred [(Swedish Landrace x Yorkshire) x Hampshire] piglets, whereas 24 control piglets were fed alpha-lactalbumin by gavage, to study the effect on growth, occurrence of postweaning diarrhea, feeding behavior, and some anatomical and physiological traits of the gastrointestinal tract. Within the litter, piglets were randomly assigned to PHA treatment or control and remained in the same pen from the beginning (PHA exposure at 7 d before weaning) until the end of the experiment (14 d post-weaning). Weaning took place at the age of 31 to 34 d. Pigs treated with PHA grew faster (P = 0.013) during the first week postweaning and tended to have lower total diarrhea scores (P = 0.10) than did control pigs. On d 5 after weaning, piglets treated with PHA spent more time eating (P = 0.028) than control pigs. No immunostimulating effect of PHA, measured by plasma immunoglobulin G, could be detected. An increase in the intestinal barrier properties before weaning, as a response to PHA treatment, was demonstrated in intestinal absorption studies using Na-fluorescein and BSA as gavage-fed markers. Less uptake (measured as plasma concentrations) of the marker molecule Na-fluorescein occurred during a 24-h study period, and numerically lower levels of BSA were observed compared with studies in control pigs of the same age. A total of 12 pigs (6 control, 6 PHA-treated) were euthanized on the day of weaning for analyses of gastrointestinal properties. The PHA-treated pigs tended to have a longer total small intestinal length (P = 0.063) than that of the control pigs. The enzyme profile of the jejunal epithelium responded to PHA exposure with a decrease in lactase activity and an increase in maltase and sucrase activities, which is similar to changes normally observed after weaning. No differences were found in the size of the pancreas or in its contents of trypsin and amylase. In conclusion, exposing piglets to crude, red kidney bean lectin for 3 d during the week before weaning led to changes in performance and small intestinal functional properties that would be expected to contribute to a more successful weaning.

Animals↗
PubMed1999

[Effect of biologically active food additives containing autolysate of baker's yeast and spirulina on intestinal permeability in an experiment].

Influence of bioactive food supplements (BFA) intake on intestinal barrier permeability to macromolecules of polyethylene glycol 4000 was studied in rats with intestinal anaphylaxis and after external gamma-irradiation. BFA studied included autolysed baker's yeast ("Vitasil") and edible algae Spirulina platensis. Intake of complex additive Vitasil + Spirulina resulted in significant diminution of permeability before irradiation and its partial normalization (24% decrease) after irradiation. Spirulina additive intake led to practically complete normalization of permeability (1.84 times decrease) in anaphylactic rats. It is concluded that Spirulina and Vitasil are promising BFA for organism general resistance elevation.

Animals↗
PubMed1996

Inflammatory cytokines, nitric oxide, and necrotizing enterocolitis.

Numerous theories have been proposed to explain the pathogenesis of necrotizing enterocolitis (NEC). Current evidence suggests that injury to the intestinal barrier as a result of various perinatal insults may facilitate invasion of the intestinal wall by bacteria. An inflammatory cascade ensues, characterized by local release of various cytokines that may contribute to further tissue destruction and hemodynamic instability in NEC. Molecular biological probes show increased expression of inducible nitric oxide synthase and interferon-gamma in the intestine of infants with NEC. Studies are planned to define the role of these inflammatory mediators in a rat model of NEC.

Animals↗
PubMed2003

Glutamine and barrier function in cultured Caco-2 epithelial cell monolayers.

Dietary glutamine (Gln) has been shown to be important for maintenance of the intestinal barrier. To investigate the role of the epithelium in this Gln dependence, Caco-2 cells were raised on semipermeable membranes under conditions that model different regions of the crypt and villus. Gln availability was controlled by addition to the medium and treatment with methionine sulfoximine to inhibit Gln synthetase (GS). Barrier function was assayed by measuring transepithelial electrical resistance and fluxes of [(14)C]mannitol and fluorescein isothiocyanate-dextran. The barrier function of these monolayers was found to require the Gln provided either in the medium at the apical or basal surface or via GS. However, the barrier was no more sensitive to Gln deprivation than it was to accumulation or maintenance of total protein. These results suggest that the in vivo dependence of the gut mucosal barrier on Gln likely involves roles separate from maintenance of the epithelial barrier per se.

Caco-2 Cells↗