Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038358 (gastric ulcer)
 5,179 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During experimental gastric ulceration in rats an elevation in the mucosal cAMP/cGMP ratio can be encountered. The cause of this significant elevation is mainly (but not entirely) the dramatic fall of the cGMP level. Similar observations were obtained with prostacyclin application (100 micrograms/kg, p.o.), too. This prostaglandin derivative is well known, among others, because of its pronounced anti-ulcerogenic (cytoprotective) effect, too. Other substances of different molecular structure and properties may also exert such effect. The exact mechanism of action of this above-mentioned cytoprotection is still not completely understood. H2-receptor blocker drug cimetidine, given in such small dose (5 mg/kg, p.o.) which does not interfere with gastric acid secretion, also exerts very significant cytoprotective effect in stress (restraint)- and drug (indomethacin)-induced gastric ulcer models. Under cimetidine effect--together with a noticeable endogenous prostacyclin mobilization--the gastric mucosal cAMP/cGMP ratio was also strongly elevated. We conclude that this elevation in the mucosal cAMP/cGMP ratio might be a possible molecular basis of the gastric cytoprotective (anti-ulcerogenic) drugs but it needs further investigations whether all substances exerting cytoprotective effect, e.g. atropine, somatostatin, sulfhydryl drugs, etc., have the same "shifting" property or not? Moreover the phenomenon of the so-called "adaptive cytoprotection" can not be ruled out completely either, therefore this problem needs attention, too.
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PMID:Gastric anti-ulcerogenic drug effect. A possible mechanism of its molecular basis. 134 9

A study is presented of the effect of copper vapors laser therapy on the content of biogenic amines--serotonin and histamine and the state of adenylcyclase (AC) system (content of cAMP, cGMP and AC activity) at the edge of the gastric ulcer. Direct effect of laser radiation (single dose 10--15 J.) produced a significant increase of serotonin, histamine, cAMP, AC activity and an insignificant increase of cGMP. Healing of the ulcerative defect after 5--6 laser therapy sessions was followed by a reduction of the content of serotonin, increase of histamine, cAMP and AC activity. The authors discuss the biostimulating effect of laser radiation by influencing the inflammatory-proliferative processes in the epitheliocytes in prolonged nonhealing gastric ulcers.
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PMID:[Biogenic amines and cyclic nucleotides in the laser therapy of long-term nonhealing stomach ulcers]. 201 85

A study was made of the effect of copper laser therapy on the content of PGE and PGF2 alpha and on the adenylate cyclase system (cAMP, cGMP and adenylate cyclase content) in patients with gastric ulcer. Seventy patients with indolent (from 3 months to 2 years) gastric ulcers were examined. The patients were assigned into 2 groups: group I received drug therapy combined with the influence of laser on copper vapours on the ulcerous surface (a single radiation dose 10 to 15 J). As compared to group I, the patients of group II manifested a considerable rise of the content of cAMP and prostaglandins, as well as adenylate cyclase activation in the gastric mucosa. Nonspecific biostimulating action of laser radiation exercised via the influence on the dysregenerative processes in the epitheliocytes of long nonhealing ulcer edges is under discussion.
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PMID:[The effect of laser therapy on the mechanisms for generating healing in long-term nonhealing stomach ulcers]. 233 23

Isolated human gastric glands provide an in vitro model that can yield significant information about the mechanisms regulating gastric acid secretion at the parietal cell level. Aminopyrine, a weak base that accumulates in acid compartments, has been used as an indirect probe of H+ secretion. By means of a microscale technique it was possible to isolate oxyntic glands from gastroscopic biopsy specimens and thereby enable studies of healthy subjects and non-operated ulcer patients. Histamine (5.4 X 10(-5) M) and db-cAMP (10(-3) M) both induced a pronounced response, whereas the response to carbachol (4.5 X 10(-6) M), although still statistically significant, was less potent. The response to stimuli was twice as high in duodenal ulcer patients as in normal individuals. In contrast, the response in patients with a gastric ulcer located either in the prepyloric region or at the minor curvature on the antrum-corpus border was of the same magnitude as in healthy subjects. Pentagastrin did not induce any response in isolated gastric glands from normal individuals. Gastric acid secretion in vitro, measured as aminopyrine accumulation, did not decrease with increasing age of the individuals.
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PMID:Acid secretion in isolated gastric glands from healthy subjects and ulcer patients. 299 68

The inhibitory effect of omeprazole on acid formation has been studied in vitro in gastric glands and partly purified H+,K+-ATPase, prepared from mucosa obtained either from healthy subjects by gastroscopic biopsy or from gastric ulcer patients during antrectomy. The effect of omeprazole was compared with the inhibitory pattern of the H2-antagonist cimetidine. Acid production in the glands was determined by measuring the accumulation of 14C-aminopyrine. In glands isolated from patients, omeprazole inhibited acid production maximally stimulated by histamine, db-cAMP, and potassium in a dose-dependent manner, with an IC50 value of about 50 nM irrespective of the agonist used. In contrast, cimetidine inhibited only histamine-induced aminopyrine accumulation, with an IC50 of about 30 micron. The inhibitory effect of omeprazole in db-cAMP-stimulated glands from healthy volunteers was of the same magnitude as seen in glands from gastric ulcer patients. Basal aminopyrine accumulation in glands from both patients and healthy volunteers was almost totally inhibited by omeprazole, whereas cimetidine was without effect. Omeprazole also concentration-dependently inhibited the H+,K+-ATPase activity in isolated gastric membrane vesicles. The estimated IC50 value was 4 micron.
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PMID:Inhibitory action of omeprazole on acid formation in gastric glands and on H+,K+-ATPase isolated from human gastric mucosa. 301 68

In HGT-1 cells incubated at 20 degrees C for 15 min with 1 mM 3-isobutyl-1-methylxanthine (IBMX), histamine (10(-4)M) increased basal cAMP levels from 2.12 +/- 0.14 to 22.9 +/- 2 pmol per 10(6) cells, with a potency of 6.4 X 10(-6)M. IBMX was added in order to inhibit cAMP degradation by low and high Km cAMP-phosphodiesterases (cAMP-PDE). The use of specific H1, H2 agonists or antagonists indicated that the histamine effect was due to an interaction with typical H2 -receptors that are involved in gastric acid secretion. Cyclic AMP levels were also increased (10-fold) by vasoactive intestinal peptide VIP (3 X 10(-11) - 10(-8)M). Porcine peptide having N-terminal histidine and C-terminal isoleucine amide (PHI) and secretin were respectively 80 and 3600 times less potent than VIP and did not produce additive effect when tested in combinations with VIP. This observation indicates that these two peptides, structurally related to VIP, are acting through the recognition sites for VIP. Combination of VIP and histamine results in additive stimulation on intact cells as well as on membrane-bound adenylate cyclase, suggesting the existence of two cell populations bearing respectively the two sets of receptors. Two other human cancer cell lines originating from nongastric tumors (HT-29 and HL-60) possess only VIP or histamine receptors, respectively, indicating the gastric cellular originality of the HGT-1 cells. It is concluded that HGT-1 cells possess both VIP and histamine H2 receptors with similar pharmacological properties to those characterized in normal human fundic glands (1,2). Therefore, this cell line can be a good model to study drugs used therapeutically during the treatment of patients for gastric ulcer or cancer.
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PMID:Histamine and VIP interactions with receptor-cyclic AMP systems in the human gastric cancer cell line HGT-1. 619 8

Gastric ulcer was provoked by indomethacine (20 mg/kg s.c.) in rats. The ulcer protection by prostacyclin and cimetidine as well as the changes of tissue cAMP level in the gastric fundic mucosa--during ulcer-provocation and ulcer protection--were studied. The animals received prostacyclin (125, 250 and 500 micrograms/kg) and cimetidine (2.5 and 50 mg/kg) together with indomethacine. Evaluation of the results was undertaken 4 hours after the administration of the provoking agent. The number and severity of the ulcers as well as the cAMP level of the gastric fundic mucosa were measured. The following results were obtained: (1) cAMP level of the gastric fundic mucosa remained unaltered at the time of ulcer provocation; (2) cimetidine and prostacyclin reduced the number and severity of the ulcers in a dose-dependent manner; (3) cAMP level of the gastric fundic mucosa was reduced after cimetidine and prostacyclin treatment in a dose-dependent manner, the extent of which however did not show any correlation with the degree of ulcer-preventive action. The experimental results indicate that (1) the development of indomethacine-induced gastric ulcer is independent of the ATP--adenylate cyclase--cAMP system of the gastric fundic mucosa; (2) the ulcer protective action of cimetidine and prostacyclin is independent of tissue cAMP system of the gastric fundic mucosa in this model.
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PMID:The relationships between indomethacine-induced gastric ulcer, ulcer protection by cimetidine and prostacyclin and the cAMP system of the gastric fundic mucosa in the rat. 630 55

The Os Sepiella maiudrone (OSM) could markedly inhibit the stress-induced gastric mucosal lesions and promote the healing of acetic acid-induced gastric ulcer in rats were reported previously. In order to demonstrate its mechanism, the effects of OSM on acidity of gastric juice, combined mucus content in gastric wall, DNA synthesis, gastric movements, the gastric contents of prostaglandin E2 (PGE2) and cAMP of gastric tissue were examined. The results showed that OSM could neutralize the gastric acid, promote the production of cAMP and PGE2 in gastric tissue. These suggested that the neutralization of gastric acid and enhancing the gastric mucosal cytoprotection by OSM would play a role in preventing and curing gastric ulcers in rats.
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PMID:[A study on Mechanism of prevention and treatment of gastric ulcer with Os sepiella in rats]. 804 5

Peptic ulcer is a common disorder of gastrointestinal system and its pathogenesis is multifactorial, where smoking and nicotine have significant adverse effects. Smoking and chronic nicotine treatment stimulate basal acid output which is more pronounced in the smokers having duodenal ulcer. This increased gastric acid secretion is mediated through the stimulation of H2-receptor by histamine released after mast cell degranulation and due to the increase of the functional parietal cell volume or secretory capacity in smokers. Smoking and nicotine stimulate pepsinogen secretion also by increasing chief cell number or with an enhancement of their secretory capacity. Long-term nicotine treatment in rats also significantly decreases total mucus neck cell population and neck-cell mucus volume. Smoking also increases bile salt reflux rate and gastric bile salt concentration thereby increasing duodenogastric reflux that raises the risk of gastric ulcer in smokers. Smoking and nicotine not only induce ulceration, but they also potentiate ulceration caused by H. pylori, alcohol, nonsteroidal anti-inflammatory drugs or cold restrain stress. Polymorphonuclear neutrophils (PMN) play an important role in ulcerogenesis through oxidative damage of the mucosa by increasing the generation of reactive oxygen intermediates (ROI), which is potentiated by nicotine and smoking. Nicotine by a cAMP-protein kinase A signaling system elevates the endogenous vasopressin level, which plays an aggressive role in the development of gastroduodenal lesions. Smoking increases production of platelet activating factor (PAF) and endothelin, which are potent gastric ulcerogens. Cigarette smoking and nicotine reduce the level of circulating epidermal growth factor (EGF) and decrease the secretion of EGF from the salivary gland, which are necessary for gastric mucosal cell renewal. Nicotine also decreases prostaglandin generation in the gastric mucosa of smokers, thereby making the mucosa susceptible to ulceration. ROI generation and ROI-mediated gastric mucosal cell apoptosis are also considered to be important mechanism for aggravation of ulcer by cigarette smoke or nicotine. Both smoking and nicotine reduce angiogenesis in the gastric mucosa through inhibition of nitric oxide synthesis thereby arresting cell renewal process. Smoking or smoke extract impairs both spontaneous and drug-induced healing of ulcer. Smoke extract also inhibits gastric mucosal cell proliferation by reducing ornithine decarboxylase activity, which synthesises growth-promoting polyamines. It is concluded that gastric mucosal integrity is maintained by an interplay of some aggressive and defensive factors controlling apoptotic cell death and cell proliferation and smoking potentiates ulcer by disturbing this balance.
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PMID:Smoking and the pathogenesis of gastroduodenal ulcer--recent mechanistic update. 1461 84

Gastric epithelial cells were incubated with a panel of clinical isolates of Helicobacter pylori, including nonulcer dyspepsia with gastritis (HS, n = 20), gastric ulcer (HU, n = 20), duodenal ulcer (HD, n = 21), and gastric cancer (HC, n = 20). HC strains induced a higher cyclooxygenase-2 (COX-2) expression than those from HS, HD, and HU. The bacterial virulence factors and the host cellular pathways were investigated. Virulence genes of iceA, vacA, babA2, cagA 3' repeat region, and hrgA failed to show any association with the disease status and COX-2 expression. Methylation-specific polymerase chain reaction revealed HC strains not affecting the methylation status of COX-2 promoter. Nuclear factor (NF)-kappaB, NF-interleukin 6, and cAMP response element were found to be involved in COX-2 induction. We explored a novel NF-kappaB activation pathway. The mutants of TLR2 and TLR9, but not TLR4, inhibited H. pylori-induced COX-2 promoter activity, and neutralizing antibodies for TLR2 and TLR9 abolished H. pylori-induced COX-2 expression. Phosphatidylinositol-specific phospholipase C (PI-PLC), protein kinase C (PKC), and Src inhibitors inhibited COX-2 induction. The dominant-negative mutants of NIK and various IkappaB kinase complexes, including IKKbeta (Y188F), IKKbeta (Y199F), and IKKbeta (FF), inhibited the COX-2 promoter activity. Phosphorylation of GST-IKKbeta (132-206) at Tyr188 and Tyr199 by c-Src was found after H. pylori infection. In summary, H. pylori induces COX-2 expression via activations of NF-kappaB, NF-interleukin 6, the cAMP response element. In NF-kappaB activation, H. pylori acts through TLR2/TLR9 to activate both the cascade of PI-PLCgamma/PKCalpha/c-Src/IKKalpha/beta and the cascade of NIK/IKKalpha/beta, resulting in the IkappaBalpha degradation and the expression of COX-2 gene. The COX-2 overexpression may contribute to the carcinogenesis in patients colonized with these strains.
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PMID:Induction of cyclooxygenase-2 overexpression in human gastric epithelial cells by Helicobacter pylori involves TLR2/TLR9 and c-Src-dependent nuclear factor-kappaB activation. 1545 96


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