Pathogenesis Of Gastric Ulcer Research Articles

Endoplasmic reticulum stress response is involved in the pathogenesis of stress induced gastric lesions in rats

Stress gastric ulcer is a serious complication, but the mechanism involved is not fully clarified. It is well known that mucosal cell apoptosis plays a crucial role in the pathogenesis of gastric ulceration. Recent studies have shown that endoplasmic reticulum (ER) stress is an important pathway leading to cellular apoptosis. To investigate the role of ER stress in the pathogenesis of stress gastric ulcer, we studied the alteration in the expression of ER stress markers GRP78 (glucose-regulated protein 78) and caspase-12 (an ER stress-specific proapoptotic molecule) and their relations with gastric mucosal apoptosis during development of stress gastric lesions in the water-immersion and restraint stress (WRS) model in rats. Rats developed severe gastric lesions after 6 h of WRS. Typical apoptosis was observed at the edge cells of WRS induced gastric lesions. Western blot analysis showed that GRP78 and activated caspase-12 were over-expressed in the gastric tissues of WRS rats. Immunohistochemical analysis demonstrated that increased GRP78 and caspase-12 were distributed only under the lesions. In addition, dithiothreitol and tunicamycin (ER stress inducers), which increased the expression of GRP78 and activated caspase-12, caused gastric mucosal injury and mucosal cell apoptosis in vitro. These findings suggest that ER stress might be involved in the development of stress gastric ulcer through an apoptotic mechanism.

Gastric hypermotility and antropyloric dysfunction in gastric ulcer patients

Impaired gastric emptying in gastric ulcer patients has generally been explained by gastric hypomotility. The gastric motor response to an electrical vagal stimulus was measured intraoperatively in patients with gastric ulcers (GU, n = 21), duodenal ulcers (DU, n = 25) and combined ulcers (GDU, n = 6). Amplitude and duration of the contraction and integrated motor response were found to be significantly greater in GU patients than in patients with duodenal and combined ulcers. Thus, hypermotility of the gastric muscle exists in GU patients and the delayed gastric emptying in GU disease may be the result of antropyloric motor dysfunction rather than of gastric hypotony. Abnormal motility associated with duodenogastric reflux appears to be a key feature in the pathogenesis of gastric ulcer.

Incidence of bile reflux in gastric ulcer and after partial gastrectomy

Duodenogastric bile reflux (DGBR) is reported to be increased in patients with gastric ulcer (GU) and following Billroth I partial gastrectomy (BIPG). pH, total bacterial counts, and total and free bile acids were measured in gastric juice aspirated hourly for 24 h in 6 patients with GU, 7 patients with a BIPG performed for GU and in 8 healthy normal controls. Intragastric pH was significantly higher in the BIPG group during the day (P less than 0.001) and at night (P less than 0.001) compared with normals and the GU group. There were no differences between GUs and normal patients. Bile acid concentrations in the gastric juice were not significantly different between GU and control groups over the 24 h. Median and range values were 0.14 (0.06-0.52) mmol l-1 in GU patients and 0.14 (0.05-0.67) mmol l-1 in the normals. However total bile acid concentrations were significantly greater in the BIPG group (0.23, 0.04-0.84) compared with GU or controls. (P = 0.04, P = 0.02). Our data do not support the role of DGBR in the pathogenesis of GU, but deoxycholic acid was detected in significantly greater amounts in BIPG subjects than controls (chi 2 = 12.94, P less than 0.001) or GU subjects (none detected) and may be important in the pathogenesis of gastric stump cancer.

Serotonin‐Containing Cells in the Gastrointestinal Tract of Newborn Foals and Adult Horses

Serotonin (5-hydroxytryptamine, 5-HT), a regulatory amine of mucosal enterochromaffin cells plays an important role in the control of gastrointestinal smooth muscle contraction and epithelial secretion. Serotonin has also been associated with gastric ulcers, diarrhoea and abdominal pain. In spite of the high incidence of these gastrointestinal disorders in newborn foals and adult horses, no data are available regarding 5-HT immunoreactive cells (i.c.) in the gastrointestinal tract (GIT) of foals, and for adult horses, data are incomplete and contradictory. In this study, the distribution and relative frequency of 5-HT i.c. in the GIT of newborn foals and adult horses were determined immunohistochemically. In foals as in adults, a relatively large number of 5-HT i.c. were detected in all portions of the GIT. In foals, a significantly higher amount of cells was found in the pyloric region and margo plicatus of the stomach, as well as in the caecum and colon ascendens compared with adults. Our results provided rationale for further research concerning the role of 5-HT i.c. during the milk diet or in the regulation of gastrointestinal growth/cell proliferation, and in the pathogenesis of gastric ulcers, especially in newborn foals.

Attenuation of Neutrophil Infiltration and Proinflammatory Cytokines byCissus quadrangularis

Reactive oxygen species, neutrophil infiltration and proinflammatory cytokines play an important role in the pathogenesis of gastric ulcers caused by aspirin. The present study demonstrates the healing effect of Cissus quadrangularis extract (CQE) through inhibitory action on generation of lipid peroxidation, proinflammatory cytokines and neutrophil infiltration. The concentration ofmalondialdehye (MDA), protein carbonyl content, conjugated dienes, mucosal (SH) sulphydryls, uric acid, tumor necrosis factor-alpha (TNF-alpha), and activities of myeloperoxidase (MPO), xanthine oxidase (XO) and antioxidative enzymes were determined in the gastric mucosa. Administration of CQE significantly attenuated the gastric lesions induced by aspirin and this was accompanied by the rise in uric acid, antioxidative enzymes, SH groups, and a significant decrease in lipid peroxidase, TNF-alpha, MPO and XO activities. These findings suggest that the significant gastroprotective activity could be mediated by the antioxidant activity as well as by the attenuation of oxidative mechanism and proinflammatory cytokines.

Pathogenesis in Portal Hypertensive Gastropathy Due to Liver Cirrhosis

The recent advances of endoscopic examination had proven that source of upper gastrointestinal bleeding in liver cirrhosis is not always caused by esophageal varices rupture but also gastric mucosal lesion. The prevalence of gastric ulcer in patients with liver cirrhosis is higher than healthy individuals. Imbalance of defensive and aggressive factors of gastric mucosa may involve in development of portal hypertensive gastropathy (PHG). Several studies reported hemodynamic changes associated wuth portal hypertension causing decreased mucus layer thickness as one of mechanism of PHG. Other etiologic factors of PHG were hypoacidity, hypergastrinemia, reduced hexosamin concentration, mucus metabolic function associated with decreased prostaglandin E2 (PGE2), and increased nitric oxyde (NO) which had caused mucus wall thickness changes. Gastric mucus damage induced by portal hypertension has important role in the pathogenesis of gastric ulcer in liver cirrhosis. Keywords : Pathogenesis, PHG, liver cirrhosis

Antioxidant effect of methanolic extract ofSolanum nigrum berries on aspirin induced gastric mucosal injury

The antiulcerogenic effects of the methanolic extract ofSolanum nigrum berries (SBE) on aspirin induced ulceration in rats with respect to antioxidant status in the gastric mucosa have been investigated. Oxygen free radicals are considered to be important factors in the pathogenesis of gastric ulcer. The level of lipid peroxides, which were elevated highly in rats with acute gastric mucosal injury was taken as an index of oxidative stress. The activities of antioxidant defense enzymes were also decreased considerably by oral gastric administration of aspirin. The decreased levels of antioxidant enzymes and increased mucosal injury were altered to near normal status upon pretreatment with (SBE) when compared to the ulcer induced rats. The results indicate that (SBE) may exert its gastroprotective effect by a free radical scavenging action. Our observations suggest that (SBE) may have considerable therapeutic potential in the treatment of gastric diseases.

Effects of hydrochloric, acetic, butyric, and propionic acids on pathogenesis of ulcers in the nonglandular portion of the stomach of horses.

To identify the pathogenesis of gastric ulcers by comparing injury to the nonglandular gastric mucosa of horses caused by hydrochloric acid (HCl) or volatile fatty acids (VFAs). Gastric tissues from 30 horses. Nonglandular gastric mucosa was studied by use of Ussing chambers. Short-circuit current (Isc) and potential difference were measured and electrical resistance calculated for tissues after addition of HCl and VFAs to normal Ringer's solution (NRS). Tissues were examined histologically. Mucosa exposed to HCl in NRS (pH, 1.5) had a significant decrease in Isc, compared with Isc for mucosa exposed to NRS at pH 4.0 or 7.0. Also, exposure to 60mM acetic, propionic, and butyric acids (pH, 4.0 or 1.5) caused an immediate significant decrease in Isc. Recovery of sodium transport was detected only in samples exposed to acetic acid at pH 4.0. Recovery of sodium transport was not seen in other mucosal samples exposed to VFAs at pH < or = 4.0. Acetic, butyric, and propionic acids and, to a lesser extent, HCl caused decreases in mucosal barrier function of the nonglandular portion of the equine stomach. Because of their lipid solubility at pH < or = 4.0, undissociated VFAs penetrate cells in the nonglandular gastric mucosa, which causes acidification of cellular contents, inhibition of sodium transport, and cellular swelling. Results indicate that HCl alone or in combination with VFAs at gastric pH < or = 4.0 may be important in the pathogenesis of gastric ulcers in the nonglandular portion of the stomach of horses.

Bright leaves, dark leaves.

The 20th century has been called the “Century of the Surgeon,” and surely it was. But who would we nominate to be the “Surgeon of the Century?” I want to place in nomination the name of a surgeon who worked in Europe and America. He developed a number of new surgical procedures, lived in four different countries during his surgical career, and studied and worked with two stalwarts in medicine. He worked in the laboratory of Ludwig Aschoff, a pioneer in pathology, and was a surgical resident and later colleague of Ernst Ferdinand Sauerbruch, an early leader in thoracic surgery. He was president of the German Surgical Society, even though he was not living in Germany at the time. He published more than 400 scientific articles in several surgical fields and in three different languages. He was editor or coeditor of 14 scientific journals, was author or coauthor of 27 books, and wrote 15 book chapters. He did pioneering research in the pathogenesis of gastric ulcer, diseases of the lungs and thorax, the origin of pulmonary emphysema, and on tuberculosis in bone and joints. In 1931, he did the first successful pneumonectomy in a human. He developed a technique for extrapleural pneumothorax for tuberculosis. Ironically, he was stricken by tuberculosis before the development of effective drug therapy, but he survived. He worked on techniques to deal with the difficult duodenal stump when partial gastrectomy was the accepted definitive therapy for intractable peptic ulcer disease. In 1937, he performed a resection of the gastric cardia and did an invaginated anastomosis. Proximal gastrectomy was well known to produce severe disabling esophagitis, but his patient did not develop it. This was to become a defining moment in his career. He left Germany, his homeland, never to live there again, and lived in Turkey, the United States, and in Switzerland. He counted among his patients Nobel Prize winners Albert Schweitzer, Albert Einstein, and pioneering radiologist Gustav Buckey. In 1955, he saw a patient with symptomatic reflux esophagitis and, recalling his 1937 patient, plicated the fundus of the stomach around the distal esophagus. This procedure not only set the stage for the best and most successful surgical treatment for reflux esophagitis—“heartburn”—but placed the surgeon’s name in the vocabulary of every general surgeon and gastroenterologist in the world. This man’s name is, of course, Rudolf Nissen. Why did a surgeon this successful entitle his biography, Helle Blatter, Dunkle Blatter—Bright Leaves, Dark Leaves (Fig. 1)? 4 Why did he leave his homeland, never to live there again? Why did he choose to live in Basel, Switzerland, for the last part of his life? How was he able to accomplish so much? What effect did his success have on his family? Rudolf Nissen was born in 1896 in Neisse, Silesia, to Dr Franz Nissen and Margarethe Borchert Nissen. Silesia was then a part of Prussia, Germany, but now is in Poland. His father, Franz Nissen, was a successful general surgeon in this quiet, tolerant city on the edge of the Carpathian Mountains. Two years after Rudolf ’s birth, his father built a clinic and hospital in Neisse. The family lived on one of the upper floors of the building, so Rudolf grew up in close contact with surgery and was inevitably drawn to it. He went to school at the katholische humanistisches Gymnasium, or Catholic high school in Neisse. The discipline of Prussia and of this school undoubtedly contributed to his strong work ethic and self-control. Perhaps, also, Immanuel Kant’s concept of “oughtness” was drilled into him at home and in school. As a young man, Rudolf thought he might like to become a painter. His father knew Fritz Erler, and sent his son to study with him at the Breslau Art Institute so that he could evaluate Rudolf ’s talent. It is likely Franz Nissen had given Erler instructions. Fritz concluded that Rudolf Nissen had enough talent to “earn his bread as a painter, but not the butter to go on it.” Rudolf began his medical studies in Breslau and then Munich, in 1913 and 1914. He volunteered for the German army to fulfill his one-year military service obligaPresented as the Presidential Address at the Texas Surgical Society, 2001.

Duodenogastric reflux following cholecystectomy in the dog: role of antroduodenal motor function.

Duodenogastric reflux has been implicated in the pathogenesis of gastric ulcer and gastritis. Duodenogastric reflux after cholecystectomy is also a possible cause of post-cholecystectomy syndrome. To investigate the role of antroduodenal motor function in increased duodenogastric reflux following cholecystectomy and the effect of trimebutine maleate (trimebutine) on the duodenogastric reflux in conscious dogs. Antropyloric and duodenal motility and bile acids content in the gastric juice were measured for 3 h during the inter-digestive state in dogs with or without cholecystectomy. Bile acids content in the gastric juice of cholecystectomized dogs was significantly higher than that of non-cholecystectomized dogs. The frequency of pyloric relaxation during phase II of the migrating motor complex was significantly increased following cholecystectomy. Intravenous infusion of trimebutine inhibited both the increased duodenogastric reflux and the frequency of pyloric relaxation in the cholecystectomized dog. Duodenogastric reflux and frequency of pyloric relaxations were increased in cholecystectomized dogs and trimebutine suppressed both of them. These findings suggest that the increased frequency of pyloric relaxation contributes to the duodenogastric reflux following cholecystectomy.

Immune response to autologous and heterologous Helicobacter pylori antigens in humans.

Infection of humans with Helicobacter pylori results in the development of chronic gastritis and plays an important role in gastric ulcer pathogenesis. Despite the infiltration of the mucosa with specific immunocompetent cells and production of specific antibodies, the infection usually persists for life. This study was performed to investigate if immunologic mechanisms exist which could contribute to the inability of the host to terminate the infection. Therefore, we compared the in vitro immunoreactivity of peripheral blood mononuclear cells (PBMC) from H. pylori-infected patients after stimulation with sonicated H. pylori bacteria from the stomach of the patient (autologous bacterial strain) with stimulation by bacteria from other patients (heterologous bacteria). We measured cell proliferation, expression of T cell activation markers CD25, HLA-DR, and CD71, as well as production ofinterleukin-10 (IL-10), an inhibitory cytokine. We found that the proliferative response of PBMC was significantly lower after autologous than after heterologous stimulation. Furthermore, secretion of IL-10 in the culture supernatants was significantly higher when PBMC were incubated with autologous than with heterologous H. pylori antigens. No significant differences between autologous or heterologous stimulation were observed in the increased expression of T cell activation markers. These data indicate that systemic immunologic response to H. pylori are strain-dependent. For further studies of the immune responses towards H. pylori, the use of an autologous stimulatory system seems necessary.

Does portal hypertension contribute to the pathogenesis of gastric ulcer associated with liver cirrhosis?

The prevalence of gastric ulcers in patients with liver cirrhosis is increased compared with that in the general population, and portal hypertension may contribute to the increased risk of gastric ulcer in cirrhosis patients. Aggressive factors involved in the pathogenesis of gastric ulcer are diminished in association with portal hypertension. In contrast, most of the important gastric mucosal defense mechanisms are shown to be impaired in portal hypertension; many of these mechanisms are also found to be altered in patients with liver cirrhosis. Portal hypotensive treatment with propranolol reduces ethanol-induced gastric mucosal damage in portal hypertensive rats and improves endoscopic signs of portal hypertensive gastropathy in cirrhosis patients. Together, these findings suggest portal hypertension-induced impairment of the gastric mucosal defenses to be an important factor in the pathogenesis of gastric ulcer in patients with liver cirrhosis. Prospective studies of portal pressure-reducing procedures, such as pharmacotherapy with propranolol, and their effect on the incidence of gastric ulcer in cirrhosis patients are needed to confirm this suggestion.

Matrix metalloproteinase expression in cultured human gastric wall fibroblasts--interactions with Helicobacter pylori isolated from patients with ulcers.

Matrix metalloproteinases (MMPs), enzymes capable of degrading collagens and other extracellular matrix components, have been implicated in gastric ulcer formation. However, the effect on MMP expression of Helicobacter pylori, also implicated in these lesions, has not been studied to our knowledge. To seek links between H. pylori and MMP expression likely to affect gastric ulcer formation. After fibroblasts from human gastric wall were cocultured with H. pylori. concentrations of MMP-1 and -2 in the medium were determined by enzyme-linked immunosorbent assays. Whereas MMP-1 was not detected in media from fibroblasts or H. pylori culture alone, MMP-1 was detected in cocultures (P<0.01). Similar amounts of MMP-2 were detected in medium from fibroblasts cultured alone and with H. pylori. No MMP-2 production by H. pylori cultured alone was detected. MMP-1 appears to be important in gastric ulcer pathogenesis, and MMP-1 induction by H. pylori may impede gastric ulcer healing.

Induction and maintenance of gastric ulceration in horses in simulated race training.

Gastric ulceration is a prevalent condition of racehorses. A number of models of gastric ulceration have been described, but none mimic the conditions of a horse in training. The objectives of this study were to determine whether gastric ulcers could be induced and maintained in a group of horses in simulated race training. In addition, serum cortisol was measured on a weekly basis to investigate the possibility that stress may be important in the pathogenesis of gastric ulceration. Thirty horses used in the trial were fed Bermuda grass hay and 6 kg of a concentrate diet, and exercised 6 days/week at speed over a distance of 1.6-2.4 km. Serum was collected and gastroendoscopic examinations performed on a weekly basis for the duration of the trial. All horses developed moderate to severe ulceration, and ulcers were maintained for the 56 day period of the trial. Only one horse had signs of abdominal discomfort, which resolved with minimal symptomatic treatment and without the use of anti-ulcer medications. Serum cortisol remained within reference ranges for the duration of the trial. Although there was some variation between the weekly examinations, serum cortisol concentrations were decreased from values obtained at the start of the trial. In this study ulcers developed without the administration of nonsteroidal anti-inflammatory agents or withholding of feed. This model provides a method to study the condition, and to investigate the effects of medications on the healing of ulcers in racehorses.

Enhanced mucosal expression of interleukin-6 mRNA but not of interleukin-8 mRNA at the margin of gastric ulcer in Helicobacter pylori-positive gastritis.

To elucidate the role of interleukin (IL)-6 and IL-8 in the pathogenesis of gastric ulcer in Helicobacter pylori-positive gastritis, in situ hybridization using digoxigenin-labeled cDNA probes for both cytokines was performed. Immunogold silver staining was added to further improve the sensitivity of this non-radioactive hybridization. The biopsy specimens were taken from eight patients with active gastric ulcer before treatment, in all of whom H. pylori was positive. Macrophages (the putative producers of these cytokines) were determined by immunohistochemistry using anti-CD68 monoclonal antibodies (KP-1). IL-6 mRNA was most abundantly expressed in the epithelium and in the infiltrating cells in tissue adjacent to gastric ulcer. Quantitative analysis disclosed a significant increase in cells positive for IL-6 mRNA near the ulcer margin compared to cells in the surrounding tissue. In contrast, cells positive for IL-8 mRNA were observed in equal proportions and evenly in the epithelium and over the entire layer of the gastric mucosa regardless of the presence of gastric ulcer. The majority of infiltrating cells positive for both IL-6 and IL-8 mRNA were thought to be macrophages because of their morphologic features and their immunohistochemical reactivity to CD68. These findings strongly suggest that IL-6 is overexpressed at the margin of gastric ulcer in H. pylori-positive gastritis.

Development of a new gastric ulcer model and the evaluation of drug effects

A new gastric ulcer model was developed by the ischemia-reperfusion procedure in rats. The ischemia-reperfusion was produced by clamping the celiac artery and subsequent removal of the clamp. Until 36 hr after the ischemia, erosive lesions were observed in the gastric glands. However, 48 and 72 hr after the ischemia, gastric ulcers involving damage of muscularis mucosae were observed. Seven days after the ischemia, the injured areas were covered with regenerated mucosa. This model may be useful for investigating the mechanisms of pathogenesis of gastric ulcer and to evaluate efficacy of drugs.

Repression of acute gastric mucosal lesions by antioxidant-containing fraction from fermented products of okara (bean-curd residue).

A crude antioxidant preparation from fermented okara (NTX) was examined for its protection against the pathogenesis of gastric ulcer in water-immersed rats. The areas of gastric mucosal lesions as well as the levels of thiobarbituric acid-reactive substances, prostaglandin E2 and hyaluronic acid in the gastric mucosa were measured in relation to the time elapsed after the imposition of stress. Comparison with those parameters in alpha-tocopherol-treated groups revealed that NTX exerted an anti-inflammatory effect on gastric injury, probably by functioning as a free radical scavenger.

An Animal Model of Gastric Ulcer Due to Bacterial Gastritis in Mice

Conventional female BalbC mice were inoculated with Gastrospirillum-like bacteria in mouse gastric homogenate or in 5.0-microns filtrate of gastric homogenate. The bacteria were originally isolated from cheetahs with gastritis. The mice were killed 6 months, 7 months, or 1 year after inoculation. All mice became infected with Gastrospirillum-like bacteria that were confined to the gastric mucosa. Control mice, given either sterile Brucella broth, 0.22-microns filtrate of infected gastric homogenate, or uninfected gastric homogenate did not become infected with bacteria. Lesions in infected mice included severe lymphoplasmacytic gastritis (26/26 infected mice), gastric epithelial hyperplasia (25/26 infected mice), and gastric ulceration (11/26 infected mice). Neutrophilic inflammatory cell infiltrates were inconsistent. None of the uninfected control mice had Gastrospirillum-like bacteria, gastritis, gastric epithelial hyperplasia, or gastric ulceration. These results implicate Gastrospirillum-like bacteria from cheetahs in the pathogenesis of gastric ulceration. This model will be useful in investigating the mechanisms of gastric ulceration associated with bacterial gastritis.

Effectiveness of Cisapride in Gastric Ulcer Results of a Double-Blind Randomized Trial Versus Ranitidine and Versus Cisapride plus Ranitidine

Among the factors involved in the pathogenesis of gastric ulcer, the reduced clearing capacity of the stomach seems to play an important role. On this basis, cisapride, which improves gastrointestinal motility, enhances gastric emptying, and prevents duodenogastric reflux, may be effective in the treatment of the gastric ulcer. We randomly allocated 60 consecutive patients, with uncomplicated antral gastric ulcer (diameter 5-25 mm), into three groups of treatment: cisapride 20 mg b.i.d. (C), ranitidine 150 mg b.i.d. (R), cisapride 20 mg b.i.d. + ranitidine 150 mg b.i.d. (C+R). Endoscopic examination with biopsy specimens was performed on admission, after 4 weeks and (if ulcer not healed) after 8 weeks of therapy. Three patients were lost to follow-up (two in C and one in C+R), and three were withdrawn, due to malignant ulcer (one case in R) or to side effects (one case of diarrhea in C, one case of headache in C+R). Healing rates at 4 weeks were 41.1% in C, 52.6% in R, and 50.0% in C+R; at 8 weeks they were 88.2% in C, 89.4% in R, and 94.4% in C+R. Though the lack of a placebo arm makes final considerations difficult, the results were similar in all three groups, with no evident differences. In conclusion, therapy with cisapride appears as effective as H2-blocker alone or combined treatments in healing benign gastric ulcer.

Prostaglandins inhibit inflammatory mediator release from rat mast cells

Background: Mast cells have been implicated in the pathogenesis of gastric ulceration. It is possible that prostaglandins exert cytoprotective effects by inhibiting the release of proulcerogenic mediators from mast cells. Methods: The effects of three prostaglandins on the release of platelet-activating factor, tumor necrosis factor, and histamine from rat mast cells (peritoneal and intestinal mucosal) activated with calcium ionophore or antigen were assessed. Results: Upon stimulation with either agonist, intestinal mucosal and peritoneal mast cells released significant quantities of platelet-activating factor. Preincubation for 5 minutes with misoprostol, prostaglandin (PG)E2, 16,16-dimethyl PGE2, ketotifen, or PF-5901 concentration-dependently reduced ionophore-stimulated platelet-activating factor release; significant effects were observed with picomolar to nanomolar concentrations of the prostaglandins and micromolar concentrations of the other compounds. Tumor necrosis factor release from peritoneal and mucosal mast cells was also significantly inhibited by the prostaglandins in picomolar to nanomolar concentrations. Misoprostol and PGE2 at concentrations of 5–50 nmol/L significantly inhibited histamine release from peritoneal mast cells stimulated with ionophore but did not affect histamine release stimulated by antigen. Conclusions: These results show potent inhibitory effects of prostaglandins on the release of pro-ulcerogenic inflammatory mediators from mast cells. Such effects may contribute to the protective and anti-inflammatory effects of prostaglandins in the gastrointestinal tract and elsewhere.