Gastric Mucosal Epithelial Cells Research Articles

MRNA expression of cytokines and chemokines in the normal gastric surface mucous epithelial cell line GSM06 during bacterial infection with Helicobacter felis

Background and aim: A group of the proinflammatory and chemotactic cytokines (chemokines) has been considered as an important factor in the pathomechanism of different bacterial diseases, among them the common Helicobacter pylori infection. Experimental results obtained with gastric biopsy samples of H. pylori positive patients, and with H. pylori infected tumor originated gastric cell lines indicated that these cytokines have essential roles in the development and maintenance of the immune response and inflammation of the gastric mucosa during H. pylori infection. Although the mRNA expression was shown in these biopsy samples and cell lines, it is not yet proved that the normal gastric mucosal epithelial cells themselves express these cytokines. The establishment of a gastric surface mucous cell line with non-tumor origin (GSM06), and the usage of Helicobacter felis as a model of the classic H. pylori infection gave us the possibility to check this question. Materials and methods: in this study GSM06 cells were infected with different numbers (10 5, 10 6, 10 7, 10 8, 10 9 bacterium/ml medium) of H. felis for two different time periods (2, 4 h). Cells treated with medium only were used as control. Then the mRNA expression of the following cytokines was measured by RT–PCR method in the GSM06 cells: proinflammatory cytokine IL1-beta, and chemokine RANTES, eotaxin, MCP-1, MIP1-alpha and MIP1-beta. Results: we found that neither mRNA of the investigated cytokines was expressed constitutively, however the GSM06 cells expressed the mRNA of each cytokine during H. felis infection. Conclusion: our results prove that normal gastric surface mucous epithelial cells express immunologically active peptides during H. felis infection. We may suppose that the epithelial cells of the gastric mucosa contribute to the immune response and inflammation by expressing proinflammatory (IL1-beta) and chemotactic (RANTES, eotaxin, MCP-1, MIP1-alpha and beta) cytokines during H. pylori infection in human.

Gastric mucosal inflammation and epithelial cell turnover are associated with gastric cancer in patients with Helicobacter pylori infection

Background—Infection with a virulent Helicobacter pylori strain is associated with gastric mucosal damage and the increased risk of gastric cancer. Aims—To examine the characteristics of host gastric mucosal responses in...

Upregulated cyclooxygenase-2 inhibits apoptosis of human gastric epithelial cells infected with Helicobacter pylori.

Helicobacter pylori induces apoptosis and alters the proliferation of gastric mucosal epithelial cells. Cyclooxygenase-2 (COX-2), the inducible form of prostaglandin (PG) synthesis, is known to cause alteration in epithelial cell growth. The goal of this study was to determine whether COX-2 gene expression by H. pylori infection could influence gastric epithelial cell apoptosis. Expression of COX-2 mRNA and proteins was up-regulated in Hs746T gastric epithelial cell lines infected with H. pylori, when assessed by quantitative RT-PCR and western blot. Inhibition of COX-2 expression using NS-398, a specific COX-2 inhibitor, showed a significant increase of gastric epithelial cell apoptosis and caspase-3 activation in Hs746T cells infected with H. pylori. Moreover, the effect of NS-398 on H. pylori-induced apoptosis was reversed by the addition of PGE2. These results suggest that up-regulated COX-2 expression by H. pylori infection can inhibit apoptosis of gastric epithelial cells.

Injection of Plasmid DNA into the Gastric Mucosa Induces Mucosal and Systemic Immunity

Nearly all mucosal surfaces participate in a common mucosal immune system, and application of an antigen to one mucosal surface elicits local as well as distant mucosal immune responses. However, whether the gastric mucosa is a part of this network has not been examined directly. We show here that the injection of plasmid DNA encoding β-galactosidase into the gastric wall caused transfection of gastric mucosal epithelial cells, induced systemic and mucosal antibody responses at both local (digestive tract) and distant (genital and respiratory tracts) sites, and induced cytotoxic T lymphocyte responses in the spleen and the mesenteric and iliac lymph nodes.

AgNOR of Human Interphase Cells in Relation to Acrocentric Chromosomes

Using simultaneous detection of fluorescence in situ hybridization (FISH) to acrocentric chromosome centromeres and argyrophilic nucleolar organizer regions (AgNOR), we investigated the number of AgNOR and involvement pattern of acrocentric chromosomes in the nucleoli in various types of human interphase cells. The number of AgNOR of normal gastric mucosal epithelial cells was 2.27 ± 1.18 and was higher than that of lymphocytes (1.08 ± 0.28) and lower than that of gastric cancer (7.76 ± 3.21). The number of acrocentric chromosome centromere signals of normal gastric mucosal epithelial cells was higher than that of normal leukocytes ( P < 0.000), and lower than that of gastric cancer ( P < 0.000). The acrocentric chromosome centromere signals in the lymphocytes and neutrophils were only half of that expected for diploid cells, perhaps related to acrocentric chromosome association. The proportion of acrocentric chromosomes attached to AgNOR in gastric cancer (0.88 ± 0.22) was significantly higher than that of normal gastric mucosal epithelial cells (0.72 ± 0.35, P = 0.007). In conclusion, acrocentric chromosome association appears to be present in circulating leukocytes even in interphase. The number of AgNORs and proportion of acrocentric chromosomes involved in AgNORs in human interphase cells may vary according to cell types. This could play a significant role in rDNA transcription and determination of cell phenotype, including malignant change.

Effect of polaprezinc ( N-(3-aminopropionyl)- l-histidinato zinc), a novel antiulcer agent containing zinc, on cellular proliferation: role of insulin-like growth factor I

The effect of polaprezinc ( N-(3-aminopropionyl)- l-histidinato zinc), a novel antiulcer drug containing zinc, on cellular proliferation was studied using cultured cells. In human umbilical vein endothelial cells (HUVEC) or human foreskin fibroblast cells, bromodeoxyuridine (BrdU) uptake and the number of cells were increased by polaprezinc under low serum conditions, but polaprezinc had no effect on guinea pig gastric mucosal epithelial cells. In addition, l-carnosine (a component of polaprezinc) had no effect on cultured HUVEC, while zinc sulfate, a representative zinc compound, increased BrdU uptake by about 2-fold at 10 −9 M. However, the action of zinc sulfate was weaker than that of polaprezinc. The insulin-like growth factor I (IGF-I) mRNA level was increased in HUVEC by polaprezinc at 10 −9 M ∼ 3 × 10 −8 M concentrations, causing stimulation of BrdU uptake. When an anti-IGF-I antibody was added to cultures, the effects of polaprezinc on BrdU uptake was suppressed. These results suggest that although polaprezinc, a novel antiulcer agent, does not have proliferative effects on epithelial cells, it does promote the proliferation of non-parenchymal cells, and IGF-I is involved in this action.

Hydrogen peroxide-induced cellular injury is associated with increase in endogenous fluorescence from rat gastric mucosal epithelial cell culture: A new method for detecting oxidative cellular injury by fluorescence measurement.

To develop a new method of detecting cellular injury caused by oxygen radicals, we studied endogenous fluorescence from the cultured cells of a rat gastric mucosal epithelial cell line. Measurement with an ultra-high sensitivity camera-image processor system under an inverted epifluorescence microscope showed that the fluorescence intensity of the cells increased time- and dose-dependently after the addition of hydrogen peroxide (H2O2), an oxygen radical precursor, to the medium. This increase was inhibited by the presence of catalase. Phase-contrast and fluorescence microscopy revealed that the fluorescence was emitted from granular substances in the cytoplasm of the injured cells. The spectral pattern of excitation and emission indicated that the fluorescent substances were flavins. In cell-free experiments, glutathione reductase which has flavin adenine dinucleotide (FAD) at the active site, increased in fluorescence after incubation with H2O2 in the presence of reduced glutathione and glutathione peroxidase. These findings indicate that FAD in the cytoplasm of cells injured by H2O2 increased in endogenous fluorescence according to the extent of injury, and suggest that fluorescence measurement may be a simple method in cellular toxicology to detect oxygen radical-induced injuries.

Activation of Epithelial Cells in Gastritis

Background: Helicobacter pylori is now recognised to be the major cause of antral gastritis and a risk factor for further development of gastric cancer. This infection results in local inflammation and a modification of gastric mucosal epithelial cell characteristics. Systematic investigation for the expression of the secretory component by gastric epithelium in a personal historical series of biopsy specimens showed the expression of this activation marker in 38% of the cases, 19% also showing clear signs of H. pylori infection. Aims: To further appreciate the activation of epithelial cells in the chronic gastric inflammation associated with H. pylori infection and other types of gastritis without consideration of the grade of gastritis. Methods: Punch gastric biopsies from 36 patients (10 patients with confirmed H. pylori gastritis, 16 patients with non-H. pylori gastritis and 10 controls) were tested for the expression of ICAM-1/CD54, HLA-DP, -DQ, -DR, secretory component and bcl-2 by immunofluorescence. Results: Up-regulation of most markers was observed both in H. pylori and non-H. pylori gastritis, although secretory component, CD54 and DP expression was more closely associated with H. pylori gastritis. Conclusion: H. pylori infection appears to activate gastric epithelial cells more strongly than other types of gastritis. This suggests an active relationship between this bacterium and epithelial cells. Investigation of the up-regulationship between this bacterium and epithelial cells. Investigation of the up-regulation of secretory component, ICAM-1/CD54 or DP in gastric biopsies may serve as extensive markers in search of H. pylori gastric infections.

Reversal of gastric somatostatin receptor inhibition by Helicobacter pylori lipopolysaccharide with ebrotidine and sulglycotide

1. 1. Among the consequences of H. pylori infection is an increase in gastric acid secretion due to the impairment in feedback inhibition by somatostatin. Here, we show that lipopolysaccharide from H. pylori inhibits the binding of somatostatin to gastric mucosal receptor, and that antiulcer agents, ebrotidine and sulglycotide, are capable of countering this effect. 2. 2. The somatostatin receptor was prepared from the solubilized gastric mucosal epithelial cell membranes by affinity chromatography on Affi-Gel-bound [D-Tryp 8]SRIF-14 and used in the binding assays for 125I-labeled somatostatin in the presence of H. pylori lipopolysaccharide and antiulcer agents. 3. 3. The assays revealed a dose-dependent inhibition in the receptor-somatostatin binding by the lipopolysaccharide which reached a maximum of 94.1%. The effect of H. pylori lipopolysaccharide was countered by ebrotidine and sulglycotide, which at their optimal doses produced 94.9% and 84% restoration in somatostatin-receptor binding, respectively. 4. 4. The results demonstrate that the antiulcer agents, ebrotidine and sulglycotide, possess the ability to counteract the H. pylori interference with somatostatin regulatory effect on gastric acid secretion.

Expression of B7-1 and B7-2 costimulatory molecules by human gastric epithelial cells: potential role in CD4+ T cell activation during Helicobacter pylori infection.

Human gastric mucosal epithelial cells display class II MHC, the expression of which is increased during Helicobacter pylori infection. These observations suggest that the gastric epithelium may participate as antigen-presenting cells (APC) during local immune responses. The increase in class II MHC expression occurs in parallel with an elevation in gastric CD4+ T cell numbers within and adjacent to the epithelium. Since the expression of either B7-1 (CD80) or B7-2 (CD86) on APC is required for the activation of T cells, it was important to establish human gastric epithelial cells expressed those surface ligands. The expression of B7-1 and B7-2 was detected on human gastric epithelial cell lines and freshly isolated epithelial cells from gastric biopsies with specific antibodies. B7-2 expression was higher than B7-1 at both protein and transcript levels and was increased after crosslinking class II MHC molecules on IFNgamma-treated epithelial cells and in cells pretreated with the combination of IFNgamma and H. pylori. Similarly, B7-2 expression was higher on gastric epithelial cells from H. pylori-infected tissues compared with those from uninfected specimens. To determine the function of these molecules on gastric epithelial cells, antibodies to B7-1 and B7-2 were shown to reduce the ability of the cells to stimulate alloreactive CD4+ T cells. These observations are the first to demonstrate that B7-1 and B7-2 are expressed on mucosal epithelial cells in situ. Thus, the expression of B7-1 and B7-2 by epithelial cells may allow them to act as APC in regulating local responses such as those that occur during infection with H. pylori.

Gene expression of keratinocyte and hepatocyte growth factors during the healing of rat gastric mucosal lesions

Background & Aims : The factors that stimulate the growth of gastric mucosal cells during gastric mucosal healing are not completely understood. This study was designed to investigate the gene expression of keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF) in the healing of gastric mucosal lesions. Methods : Northern blot analysis and reverse-transcription polymerase chain reaction were used to show HGF and KGF messenger RNA. Results : Transcripts of HGF and KGF were not shown in rat gastric mucosal epithelium but were found in submucosal and muscular layers under normal conditions. When acute gastric mucosal lesions were induced by indomethacin treatment, expression of HGF messenger RNA was augmented in submucosal, muscular, or serosal layers, whereas the transcript of KGF was not influenced. When rat gastric mucosal epithelial cell line RGM1 and rat gastric mucosal primary culture cells were incubated with HGF or KGF, their proliferation was enhanced. Conclusions : The results showed increased gene expression of HGF together with constant production of KGF during gastric mucosal healing.

自家蛍光による消化管病変の診断と治療

Backgrounds: Autofluorescences of endogenous porphyrins and. flavins were reported to appear in accordance with oxygen radical induced mucosal injuries in ischemia-reperfusion stress. Using the cultured cells of a rat's gastric mucosal epithelial cell line, we examined a relations between the endogenous cellular fluorescence and cellular injury caused by oxygen radicals. Moreover, we also elucidate relations between porphyrins' fluorescence and intestinal lesions, and examine the clinical applicability of this phenomenon in endoscopy. Methods: Fluorescence intensity of a rat gastric mucosal cell line RGM1 was measured with an ultra-high sensitivity camera-image processor system under a microscope. Cellular fluorescence spectrum were also analyzed. Patients of colon carcinoma, colon adenoma and ischemic colitis in University of Tsukuba Hospital were removed pieces of colon mucosae. which were observed with a microscope. Extracts from these specimens were also analyzed with a spectrofmeter. Results: The cellular fluorescence intensity increased in accordance with H2O2 induced cellular injury. Fluorescent substances were indicative of flavins from the spectral pattern of excitation and emission. Mucosae of all these lesions emitted obvious fluorescence and showed statistical significant difference in comparison with normal mucosae. In particular, fluorescence of ischemic colitis was strong and different significantly from the other lesions. Fluorescent substances were decided as porphyrins and flavins with spectroanalyses. Conclusions: These findings indicate that FAD in the cytoplasm of cells injured by H2O2 increased in endogenous fluorescence according to the extent of injury, and suggest that fluorescence measurement can be a simple method of cellular toxicology to detect oxygen radical-induced injuries. Colon mucosal lesions were able to detect with the fluorescence endoscopy-image analyzing system. This system can show a highly sensitive diagnosis in endoscopy. The stronger fluorescent mucosa of ischemic colitis patients suggests that mechanisms of this phenomenon came from oxygen radicals.

Sucralfate Counteracts the Inhibition of Gastric Mucosal Mucin Receptor byHelicobacter pyloriLipopolysaccharide

Among the disturbances in gastric mucosal defense associated with Helicobacter pylori infection is the loss of mucus coat continuity, which results in a severe disturbance in the ability of mucus coat to maintain its functions as the pre-epithelial element of gastric mucosal defense. Here, we show that H. pylori, through its cell-wall lipopolysaccharide, disrupts the interaction between gastric mucin and its mucosal receptor, and that sucralfate is capable of counteracting this untoward effect of the bacterium. The receptor was isolated from octylglucoside-solubilized gastric mucosal epithelial cell membranes by affinity chromatography on Sepharose-bound wheat germ agglutinin and following iodination with 125I, used in the binding assays for mucin in the presence of H. pylori lipopolysaccharide and sucralfate. Preincubation of the receptor protein with H. pylori lipopolysaccharide led to a decrease in mucin binding. The inhibitory effect was proportional to the concentration of lipopolysaccharide and reached a maximum of 91% at 30 micrograms/ml. The effect of H. pylori lipopolysaccharide was countered by sucralfate, which caused a dose-dependent relief of the inhibitory effect. The maximum (75%) restoration in mucin-receptor binding occurred at 60 micrograms/ml sucralfate. The results provide strong evidence for the effectiveness of sucralfate in preventing the loss of gastric mucus coat continuity caused by H. pylori.

Enhancement by thyroxine of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

The affects of L-thyroxine (T4) on the incidence and histology of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), and on the labelling index of gastric mucosal epithelial cells were investigated in Wistar rats. After oral treatment with MNNG for 25 weeks, the rats received s.c. injections of T4 (0.2 microgram kg-1) in depot form every other day until the end of the experiment in Week 52. This long-term treatment with T4 significantly increased the incidence of gastric cancers in Week 52. However, it did not influence the histological type of the gastric cancers. It also caused significant increases in the labelling indices of the fundic and antral epithelial cells. These findings indicate that T4 enhances the development of gastric cancers, and that its effect may be related to its effect in increasing proliferation of gastric epithelial cells.

Reconstitution of an epithelial chloride channel. Conservation of the channel from mudpuppy to man.

We have previously shown that monoclonal antibody E12 (MAb E12), one of several such antibodies raised against theophylline-treated Necturus gallbladder (NGB) epithelial cells, inhibits the chloride conductance in the apical membrane of that tissue. Since chloride channels are critical to the secretory function of epithelia in many different animals, we have used this antibody to determine whether the channels are conserved, and in an immunoaffinity column to isolate the channel protein. We now demonstrate that MAb E12 cross-reacts with detergent-solubilized extracts of different tissues from various species by enzyme-linked immunosorbent assay (ELISA). Western blot analysis shows that this monoclonal antibody recognizes proteins of Mr 219,000 in NGB, toad gallbladder, urinary bladder, and small intestine, A6 cells, rat colon, rabbit gastric mucosa, human lymphocytes, and human nasal epithelial cells, and inhibits the chloride conductance in toad gallbladder, rat colon, and human nasal epithelium. Detergent-solubilized protein eluted from an immunoaffinity column and then further purified via FPLC yields a fraction (Mr 200,000-220,000) which has been reconstituted into a planar lipid bilayer. There it behaves as a chloride-selective channel (PCl/PNa = 20.2 in a 150/50 mM trans-bilayer NaCl gradient) whose unit conductance is 62.4 +/- 4.6 pS, and which is blocked in the bilayer by the antibody. The gating characteristics of this channel indicate that it can exist as aggregates or as independent single channels, and that the antibody interferes with gating of the aggregates, leaving the unit channels unchanged. From these data we conclude that the protein of Mr 219,000 recognized by this monoclonal antibody is an important component of an epithelial chloride channel, and that this channel is conserved across a wide range of animal species.

Influence of pineal indoleamines on the mitotic activity of gastric and colonic mucosa epithelial cells in the rat: Interaction with omeprazole

We have investigated the effects of melatonin (Mel) and N-acetylserotonin (NAc-5HT) on the mitotic activity of gastric and colonic mucosa in adult male rats under basal conditions and after an administration of omeprazole (OM) (H+,K(+)-ATPase inhibitor). The metaphase-arrest technique was applied in the study. Additionally, serum gastrin levels were measured by RIA method in the OM-treated group and in respective polyethyleneglycol (PEG)-administered controls. We have found that: 1) OM-treatment increased serum gastrin levels in rats; 2) OM enhanced the mitotic activity of the colonic mucosa cells, although, unexpectedly, it did not exert such an effect on the gastric mucosa cells; 3) Mel suppressed the OM-induced increase of the colonic epithelium cell proliferation, while NAc-5HT failed to reveal that action: 4) NAc-5HT decreased the proliferation of gastric mucosa epithelial cells. The value of the mean mitotic activity rate (MMAR) of gastric mucosa after Mel-treatment also decreased, but that change was not statistically significant. The obtained data are in compliance with previous results from our laboratory concerning the inhibitory effect of pineal indoleamines on the jejunal epithelium mitotic activity. The stimulatory effect of OM on the proliferation of colonic epithelium is probably mediated by OM-induced hypergastrinaemia. The possibility of Mel interaction with intestinal gastrin receptors (a structural similarity occurs between Mel and benzotript, a specific gastrin receptor antagonist), as well as of the opposite effects of Mel and gastrin on intracellular cAMP content in the gut, are considered in the discussion of results.

Study of Wheals on Gastric Mucosa in Patients with Chronic Uticaria by Scanning and Transmission Electron Microscopy

Urticarial wheal is due to the leak of proteins and fluids to extravascula by increased capillary permeability. Edematous erythema and wheals located in the surface of gastric mucosa were observed by gastroscopy. The present contribution is the first in the international extent of the observation of wheals on gastric mucosa of 38 patients with chronic urticaria with the transmission electron microscope (TEM) and scanning electron microscope (SEM).Gastroscopies were performed on 38 patients with chronic urticaria during episodes ofcutaneous wheals. Biopsy specimens were taken from gastrical wheals from 38 patients. The EM specimens were routinely prepared. Linder the SEM, the surface of the epithelial cells of wheals on the gastric mucosa appeared slightly edematous and rough. Intercellular space of the epithelium became more narrow and shallow. The structure of microvillae on gastric mucosa epithelial cells could be seen, but appeared short and decreasing in amount. Under the TEM, it was found that the stomach mucous membrane was edematous.

Quantitative immunogold localization of laminin and Type IV collagen in gastric mucosa

Upon exposure to alcohol, necrotic lesions form in the gastric mucosa and surface epithelial cells detach leaving an exposed basal lamina. Since the basal lamina acts as a scaffold during restitution and repair in other organs, it may play a significant role in gastric tissue recovery, directing epithelial cell migration to the denuded surface. Type IV collagen and laminin are two of the major macromolecules which compose the basal lamina type IV collagen furnishes strength and flexibility, while laminin functions in cell adhesion and migration. However, despite the likely role of the basal lamina in gastric tissue restitution and repair, it has not been studied as a target of alcohol injury. The technique of TEM immunocytochemistry enabled us to quantify the response of the basal lamina to acute alcohol through examining ensuing changes in immunogold labelling (IG) to type IV collagen and laminin in rat gastric mucosa.Female Sprague-Dawley rats weighing 180-200 g were fasted overnight. The next day 1 ml of 50%, 100% ethanol (50E, 100E) or saline (S) was administered via orogastric tube. After either 5 or 60 min, anesthetized animals were perfused with fixative. For IG studies, gastric tissues were fixed with 1% paraformaldehyde, which is known to preserve the antigenicity of basal lamina components. Since ultrastructural characteristics were not optimal with this fixative, however, parallel TEM studies were also executed using standard techniques. Tissues for IG studies were embedded in Lowicryl K4M at -30°C, sectioned, and incubated in anti-type IV collagen or anti-laminin followed by protein A-gold. Uranyl acetate-stained sections were viewed on a JEOL 1200EX TEM at 60kV. Micrographs from the interfoveolar, pit and gland isthmus regions of the gastric mucosa were examined at 30,000x, the area of lamina densa measured and number of gold particles per area counted. Results were analyzed using analysis of variance and Student-Newman-Keuls’ test for multiple comparisons (α= 0.05).

Do mild irritants protect surface epithelial cells of gastric mucosa against ethanol-induced damage in rat? An ultrastructural study of adaptive cytoprotection.

Do mild irritants protect surface epithelial cells of gastric mucosa against ethanol-induced damage in rat? An ultrastructural study of adaptive cytoprotection.

Gastric surface epithelial cell damage induced by restraint and water-immersion stress in rats. Protective effects of 16,16-dimethyl-prostaglandin E2.

The time course of gastric mucosal surface epithelial cell damage and macroscopically visible lesions in response to restraint and water-immersion stress (22 degrees C) in rats was examined, and the prophylactic effects on it of 16,16-dimethyl-prostaglandin E2 (dmPGE2) were compared with those of papaverine, timoprazole, and atropine. The stress produced surface epithelial cell damage prior to visible lesion, the former increasing in severity with time and reaching a plateau 60 min later, by which time exfoliation of surface epithelial cells was observable along the mucosal folds. In contrast, macroscopically visible lesions appeared 2 h after stress, and severity continued to increase with time. Pretreatment injections (s.c.) of dmPGE2 (3 and 30 micrograms/kg), papaverine (100 mg/kg), and atropine (1 mg/kg) protected the surface cells against stress-induced (1 h) damage, and inhibited visible lesion formation after 4 h stress. Timoprazole (30 mg/kg s.c.) did not protect the surface cells, but did markedly inhibit visible lesion formation. DmPGE2, papaverine, and atropine, but not timoprazole, inhibited stress-induced increases in gastric contractions. DmPGE2, timoprazole, and atropine, but not papaverine, inhibited acid secretion in stress conditions. These results indicated that stress induced damage to the gastric mucosa within 1 h due to increased gastric contractions, and the surface epithelial cell damage developed into macroscopically visible lesions in the presence of acid, and that dmPGE2 protected the surface epithelium against stress-induced damage probably by inhibiting gastric contractions.