Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autoimmune gastritis, leading to pernicious anaemia, is an organ-specific autoimmune disease characterized by chronic atrophic gastritis and circulating gastric parietal cell autoantibodies. The parietal cell autoantigens have recently been identified as the alpha and beta subunit of the gastric proton pump (H+, K+ ATPase). Here Paul Gleeson and Ban-Hock Toh discuss how the identification of these gastric parietal cell autoantigens and the development of a mouse model of autoimmune gastritis have paved the way for an understanding of the pathogenesis of the gastric lesion.
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PMID:Molecular targets in pernicious anaemia. 165 72

The effects of ellagic acid on gastric H+, K(+)-ATPase, acid secretion, and the occurrence of gastric ulcers were studied. Ellagic acid inhibited hog gastric H+, K(+)-ATPase activity with a 50% inhibition at 2.1 x 10(-6)M; kinetic studies showed that the inhibition of H+, K(+)-ATPase by ellagic acid is competitive with respect to ATP and is noncompetitive with respect to K+. The effect on gastric ulcers was investigated by using a stress ulcer model. Intraperitoneal administration of ellagic acid at above 5 mg/kg markedly reduced the occurrence of gastric lesion. Ellagic acid significantly reduced acid secretion at the same doses. These results suggest that ellagic acid has a marked inhibitory effect on acid secretion and the occurrence of stress-induced gastric lesions, and these effects may be attributed to the inhibition of H+, K(+)-ATPase activity.
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PMID:Inhibition of gastric H+, K(+)-ATPase and acid secretion by ellagic acid. 166 31

Salvianolic acid A, a depside from the roots of Salvia miltiorrhiza, inhibited pig gastric H+,K(+)-ATPase and pNPPase with 50% inhibition values (IC50) of 5.2 x 10(-7) M and 1.7 x 10(-6) M, respectively. Kinetic studies revealed that the inhibition patterns induced by salvianolic acid A were competitive with respect to ATP and noncompetitive with respect to K+. Salvianolic acid A (25 mg/kg, i.p.) significantly inhibited acid secretion in pylorus-ligated rats. At the same dose it also showed a significant reduction in the formation of gastric lesion induced by water immersion and restraint stress. These results suggest that salvianolic acid A shows antisecretory and antiulcer activity by inhibiting the gastric H+,K(+)-ATPase.
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PMID:Effect of salvianolic acid A, a depside from roots of Salvia miltiorrhiza, on gastric H+,K(+)-ATPase. 217 8

Autoimmune gastritis induced by neonatal thymectomy of mice is a CD4+ T cell-mediated organ-specific autoimmune disease. The characteristic features of autoimmune gastritis, which include a mononuclear infiltrate within the gastric mucosa, loss of parietal and chief cells and circulating autoantibodies to the gastric H+/K+ ATPase, appear 6-10 weeks after thymectomy. Here we have assessed the role of interferon-gamma (IFN-gamma) in the pathogenesis of the gastric lesion. Splenic T cells derived from mice with gastritis produced three- to tenfold more IFN-gamma than T cells from normal animals after stimulation with anti-CD3 antibodies. Treatment of neonatally thymectomized mice at weekly intervals for 6 or 12 weeks with a neutralizing rat monoclonal antibody to mouse IFN-gamma abolished the production of anti-gastric autoantibodies and decreased the incidence of gastric mononuclear infiltrates from the 69% observed in normal rat immunoglobulin (Ig)-injected mice to 16%. Further, in mice treated with only a single dose of anti-IFN-gamma immediately after thymectomy at 3 days after birth, the incidence of autoimmune gastritis was 1/19 compared to 8/19 in normal rat Ig-injected mice. Prevention of autoimmunity by neutralization of IFN-gamma several weeks prior to the detection of a pathological lesion strongly suggests that IFN-gamma plays an essential role in the initiation of the gastric autoimmune response.
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PMID:Interferon-gamma is required during the initiation of an organ-specific autoimmune disease. 876 75

Autoimmune gastritis induced in BALB/c mice by neonatal thymectomy is a CD4+ T cell-mediated disease. The disease is characterised by mononuclear cell infiltrates in the gastric mucosa, loss of gastric parietal and chief cells and autoantibodies to the gastric H/K ATPase. Here we describe a simple non-enzymatic method for isolating cellular infiltrates from stomachs of gastric mice by injection of medium directly into stomach walls, causing swelling and rupture. Using this method, large numbers of viable lymphocytes were released from stomachs for analysis by flow cytometry. An 8.3 fold increase in the total number of lymphocytes from diseased stomachs compared to normal controls was observed. Total cell numbers of CD4+ and B cells were increased 4.8 fold and 39.5 fold respectively, in diseased stomachs compared with controls. No change was observed in the CD8+ T cell population. This method will allow detailed quantitative analysis of cellular infiltrates during the development of the gastric lesion and enrichment of pathogenic T cells for analysis and cloning. This procedure may have general application for the isolation of cellular infiltrates from lesion sites of other organs.
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PMID:A novel method for isolating mononuclear cells from the stomachs of mice with experimental autoimmune gastritis. 882 79

Murine autoimmune gastritis, induced by neonatal thymectomy, is characterized by a mononuclear infiltrate within the gastric mucosa, loss of parietal and zymogenic cells and circulating autoantibodies to the gastric H/K ATPase. The infiltrate contains both CD4+ and CD8+ T cells. Here we have investigated the roles of CD4+ and CD8+ T cells in the development of gastritis by in vivo treatment with depleting rat anti-CD4 and anti-CD8 monoclonal antibodies. Depletion of CD4+ T cells decreased the incidence of gastric mononuclear infiltrates from 63% (5/8), observed in normal rat immunoglobulin G (IgG)-injected mice, to 8% (1/12) and also abolished the production of antigastric autoantibodies. In contrast, depletion of CD8+ T cells did not reduce the incidence of gastritis. The absence of CD8+ T cells in the infiltrate of the stomach of anti-CD8(+)-treated mice was confirmed by immunocytochemistry. These results argue that neonatal thymectomy-induced autoimmune gastritis is mediated by CD4+ T cells and that CD8+ T cells do not play a significant role in the development of the gastric lesion.
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PMID:CD4+ T cells, but not CD8+ T cells, are required for the development of experimental autoimmune gastritis. 964 Feb 52

The mucosal protective effect of nitric oxide (NO) was examined by using N(G)-nitro-L-arginine methyl ester (L-NAME) as nitric oxide synthase (NOS) inhibitor and nitroprusside (NP) as NO donating agent, in ethanol-induced rat gastric lesion model. The results are summarized as follows: (1) As gastric tissue samples were examined by light microscopy, intragastric exposure of ethanol was demonstrated to induce gastric injury, which was more prominent in female rats. The depletion of NO by L-NAME treatment exacerbated the ethanol-induced gastric lesion but NP together with ethanol promoted repair of the mucosal injury, especially in female rats. (2) Gastric H+, K+ -ATPase enzyme activity, which was responsible for acid secretion, seemed not to be effected by ethanol treatment. Together with ethanol, L-NAME treatment activated, whereas NP treatment inhibited, the enzyme activity in female rats. (3) Ethanol treatment inhibited gastric alcohol dehydrogenase (ADH) activity, which was responsible for the first-pass metabolism of ethanol. Together with ethanol, L-NAME did not effect the enzyme activity whereas NP treatment disappeared the inhibitory effect of ethanol in both gender. Hydroxyl radical (OH*) scavenger activity was found to increase in ethanol and ethanol + NP groups in both sexes, but superoxide radical (O2-*) scavenger activity did not change. The results indicate that NO may ameliorate the damaging effect of ethanol possibly by regulating acid secretion, ethanol metabolism, and antioxidant content in rat gastric mucosa.
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PMID:Nitric oxide-mediated regulation of gastric H+, K+ -ATPase and alcohol dehydrogenase following ethanol-induced injury in rats. 1048 28

The efficacy of a paste formulation of the H+, K+, -ATPase inhibitor omeprazole was evaluated in standardbred racehorses for the treatment and prevention of gastric ulcers. Twenty standardbred racehorses in training, aged 2 to 9 years, were enrolled from 2 training centres in this field trial. Endoscopic examinations confirmed the presence of gastric ulcers in all horses, prior to allocation and treatment and on day 0. Lesions were scored on a scale of 0 to 3 (intact epithelium to extensive ulceration). Replicates were formed, based on training level and location. Within replicates, 1 horse was assigned to group 1 and 3 horses were assigned to group 2, randomly. Horses in group 1 were sham-dosed controls. Horses in group 2 were given omeprazole paste orally at 4 mg/kg bodyweight (BW)/day from day 0 to day 27 and 2 mg/kg BW/day of omeprazole paste orally from day 28 to day 57. Follow-up endoscopies were conducted on post treatment days 28 and 58 or 59. Physical examinations, including BWs, were conducted on all horses prior to treatment and on days 13 or 14, 28, 42 or 43, and 58 or 59. Horses treated with omeprazole had significantly (P < 0.01) more improvement in gastric lesion scores than did controls at day 28 and at study termination on days 58 or 59. All of the omeprazole-treated horses were improved relative to baseline ulcer score at both examinations, and 73.3% were healed (lesion score of 0) at both examinations. None of the controls improved at any point during the study. When the dose was reduced to 2 mg/kg BW, 80% of the horses showed no recurrences or worsening in gastric ulcers. It was concluded that omeprazole paste at 4 mg/kg BW orally, once daily is highly effective in healing gastric ulcers in standardbred racehorses in training and that a dose of 2 mg/kg BW orally, once daily, effectively prevents the recurrence of gastric ulcers in most horses.
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PMID:Efficacy of a paste formulation of omeprazole for the treatment of naturally occurring gastric ulcers in training standardbred racehorses in Canada. 1289 89

The gastrointestinal activity of hydroalcoholic extract (HE) of Salvia officinalis was evaluated in a model of ethanol-induced gastric lesion. HE showed excellent activity, with ID(50) 84.0 (54.8-128.9) mg/kg. The acetic acid-induced ulcer and the total acidity of the gastric secretion were also reduced by HE, and, in vitro experiments, the H(+),K(+)-ATPase activity was inhibited. Carnosol was identified as a possible active constituent for the gastroprotective effect of HE.
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PMID:Gastroprotective constituents of Salvia officinalis L. 1948 90

Autoimmune gastritis is the outcome of a pathological CD4 T cell-mediated autoimmune response directed against the gastric H/K-ATPase. Silent initially, the gastric lesion becomes manifest in humans by the development of megaloblastic pernicious anemia arising from vitamin B12 deficiency. Cutting edge issues in this disease relate to its epidemiology, immunogenetics, a role for Helicobacter pylori as an infective trigger through molecular mimicry, its immunopathogenesis, associated organ-specific autoimmune diseases, laboratory diagnosis, and approaches to curative therapy.
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PMID:Cutting edge issues in autoimmune gastritis. 2117 35


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