Search

Regulation of gastric epithelial permeability is important in the protection of the gastric mucosa from secreted acid. However, the mechanism(s) for this regulation in gastric mucus cells remains unknown. In this study, we evaluated gastric epithelial-cell permeability in response to acid exposure by monitoring trans-epithelial electrical resistance (TEER) and paracellular permeability with carbon 14-labeled mannitol. We also examined the role of prostaglandins on gastric epithelial permeability. Rat gastric epithelial cells (RGM-1) were plated on 8-microm-pore tissue-culture inserts. Cells were exposed to solutions of differing pH (3-7.4), with and without the nonsteroidal antiinflammatory drug (NSAID) indomethacin (10(-7) mol/L), for 60 to 120 minutes. Transepithelial permeability was measured on the basis of TEER and the diffusion rate of [(14)C]mannitol. Prostaglandin E(2) (PGE(2)) was administered in some experiments with NSAIDs. After acid exposure (pH 3.0-5.0), TEER rapidly and significantly increased, peaking in 5 minutes. Diffusion of [(14)C]mannitol was blocked during the period when TEER increased. Pretreatment with the cyclooxygenase (COX) inhibitor indomethacin blocked the rapid acid-induced increase in TEER. A specific COX-2 inhibitor had no effect on this rapid increase in TEER. The blockade by indomethacin was eliminated by the addition of PGE(2). These findings suggest that when gastric-surface mucus cells are exposed to acid, gastric epithelial permeability decreases rapidly to inhibit acid back-diffusion. Prostaglandins play an important role in this protective response to acid exposure. COX inhibitors such as indomethacin may inhibit the regulation of epithelial permeability by reducing the concentration of PGE(2).

Background and Aim: It is well known that capsaicin-sensitive nerve signaling acts as a protective factor against various ulcerogens. However, the contribution of topical capsaicin-sensitive nerves within the stomach to rapid restitution has not been fully investigated. The present study was therefore conducted focusing on recovery from gastric mucosal damage induced by ethanol in vivo., Methods: Male Sprague-Dawley rats were fasted and anesthetized. 51Cr-EDTA was administered intravenously and gastric mucosal integrity was continuously monitored by measuring the blood to lumen 51Cr-EDTA clearance. Capsaicin or vehicle was irrigated before, together with or after the perfusion of 20% ethanol, followed by perfusion with saline. In another experiment, ruthenium red, a capsaicin-sensitive cation antagonist, was given before the ethanol-capsaicin perfusion. Furthermore, this study was verified using lafutidine, a histamine H2-receptor antagonist, which has a gastric mucosal protective action through the capsaicin-sensitive afferent nerves., Results: When capsaicin was administered before ethanol treatment, mucosal damage was significantly reduced and recovery was significantly rapid compared to the control. When capsaicin (160 micro M) and ethanol were administered simultaneously, the mucosal damage was exacerbated but recovery was nevertheless more rapid than the control group. With a lower dose of capsaicin (80 micro M), mucosal damage was not exacerbated and recovery was enhanced. When capsaicin or lafutidine was administered after the induction of ethanol injury no change was detected regarding the damage. However, recovery was significantly accelerated. Ruthenium red reversed the action of post-treatment with capsaicin on restitution., Conclusions: These results indicate that luminal administration of capsaicin exerts protection against and accelerates restitution from gastric damage in the very early phase after ethanol injury. This action is probably due to activation of topical capsaicin-sensitive afferent nerves in the rat.

Background and Aim: E-cadherin expressed on gastric epithelium is reported to form adherence junctions and stabilize barrier functions. While hypoxia-reoxygenation is well known to cause gastric mucosal injury during reoxygenation, gastric E-cadherin actions against this stress remain unclear. In this study, using the oxygen depleting agent thioglycolic acid we examined whether E-cadherin expressed on rat cultured gastric epithelial cells has protective actions against epithelial barrier dysfunction induced by chemical hypoxia-reoxygenation., Methods: Chemical hypoxia was induced by incubating cells with 5 mm thioglycolic acid in glucose free medium for 60 min. Cells were then reoxygenated for 240 min by changing to normal medium. The expression of E-cadherin on the cell surface was measured with an enzyme immunoassay, and epithelial permeability was determined by the diffusion rate of FITC-dextran through the cell layer., Results: E-cadherin expression increased during the 60 min hypoxic period, accompanied by activation of protein kinase C, protein kinase G and protein kinase A. The increased expression significantly diminished, but was considerably higher than the control values during reoxygenation for 180 min, which was partially due to generation of reactive oxygen species but not to activation of protein kinase. Conversely, epithelial permeability was stabilized during hypoxia, but increased only for 30 min of reoxygenation, probably due to generation of reactive oxygen species. Epithelial permeability during hypoxia was elevated by a combination of all the protein kinase inhibitors., Conclusion: An increase in the expression of E-cadherin during hypoxia through the activation of the kinases is likely to stabilize epithelial barrier functions. The reactive oxygen species generated during 30 min reoxygenation increased the molecular expression of E-cadherin less than during hypoxic stress. The transient break in the barrier functions caused by reactive oxygen species during reoxygenation appears to overcome the reactive oxygen species mediated cytoprotective action increasing E-cadherin expression.

AbstractBackground: The role of complement in ischaemia–reperfusion injury has not been well investigated. 5I2 is a monoclonal antibody (mAb) directed against a rat membrane inhibitor of the C3 convertase step, which is the rat counterpart of mouse Crry/p65. 6D1 is a mAb against rat CD59 which inhibits the formation of membrane attack complexes. Methods: We visualized the tissue distribution of these membrane inhibitors in rat gastrointestinal tract by immunohistochemical staining with the appropriate mAb. Then, we tested the hypothesis that complement regulatory proteins protect rat gastric mucosa against ischaemia–reperfusion stress by using these mAbs. Gastric mucosal integrity was continuously monitored by measuring the blood-to-lumen clearance of [51Cr]-labelled ethylenediaminetetraacetic acid (EDTA) under control conditions, during ischaemia and after reperfusion. Results: Rat 6D1 and 5I2 antigens were both widely distributed and predominantly expressed on smooth muscle and endothelial cells in gastrointestinal tracts. Blockade of complement regulatory proteins with 5I2 and 6D1 mAbs resulted in a significant increase in [51Cr]-EDTA clearance after reperfusion. Conclusions: These findings support the hypothesis that endogenous complement regulatory proteins may act as important protective factors against ischaemia–reperfusion stress in rat gastric mucosa. © 1999 Blackwell Science Asia Pty Ltd. [ABSTRACT FROM AUTHOR]