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 develops spontaneously in approximately 60% of BALB/c mice thymectomized neonatally. Histologically and clinically it is similar to the atrophic gastritis associated with pernicious anaemia in humans. Here we identified antigenic protein relating to the pathogenesis of autoimmune gastritis in these mice. All sera from 32 thymectomized mice with gastritis contained autoantibodies to the vesicular fraction prepared from rat gastric parietal cells. Immunoblot analysis revealed all of these to react with a 94-kD protein corresponding in molecular mass with the H+/K(+)-ATPase alpha subunit. Some sera were also reactive with 65-85-kD and/or 60-kD proteins, whose sizes correspond to the H+/K(+)-ATPase beta subunit and intrinsic factor, respectively. The finding that immuno-adsorption with these sera resulted in reduction of H+/K(+)-ATPase activity in the vesicular fraction, supported a conclusion of H+/K(+)-ATPase alpha and/or beta subunits as the antigenic proteins. After immunization of normal syngeneic mice with various doses of gastric parietal cells or their vesicular fraction, all sera from animals demonstrating atrophic gastric mucosa with lymphocyte infiltration reacted with the H+/K(+)-ATPase alpha subunit. No antibodies to other proteins were induced even in mice immunized with higher doses of antigen. We therefore conclude that H+/K(+)-ATPase alpha subunit is important as the target antigen in pathogenesis of autoimmune gastritis in neonatally thymectomized mice, probably due to a high affinity for the MHC molecule.
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PMID:Involvement of the H+/K(+)-ATPase alpha subunit as a major antigenic protein in autoimmune gastritis induced by neonatal thymectomy in mice. 132 Oct 13

Little data exists regarding the activity of gastric parietal cells in the very immature infant. Therefore we have examined the developing human stomach for the presence and location of parietal cells, using both standard histological methods and antibodies to the H+/K+ ATPase (proton pump) and intrinsic factor, in 35 fetuses (ranging from 13-28 weeks) and in five infants (2-21 weeks). Parietal cell activity was noted in the body, antrum and pyloric regions in all the fetal specimens examined. However, this activity was much more limited in the infant specimens. We have noted that from the end of the first trimester parietal cells are present in a mature, functional form with the potential to secrete both gastric acid and intrinsic factor.
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PMID:Gastric secretory function in the developing human stomach. 133 42

Intrinsic factor is produced by the gastric parietal cell. Its secretion is stimulated via all pathways known to stimulate gastric acid secretion: histamine, gastrin, and acetylcholine. There is, however, a different mode of secretion for both substances: atropine, vagotomy, and H2 receptor antagonists inhibit both intrinsic factor and acid secretion, but secretin and the hydrogen-potassium ATPase antagonist omeprazole have no effect on intrinsic factor while substantially reducing acid secretion. Cobalamin in food is bound to animal protein. Cobalamin deficiency due to inadequate dietary intake is rarely seen in extreme vegetarians (vegans). In the stomach cobalamin is liberated from its protein binding by peptic digestion and bound to R-proteins. Hypochlorhydria or achlorhydria, whether medically induced or not, may impair cobalamin uptake. The cobalamin-R-protein complex is split by pancreatic enzymes in the duodenum, where cobalamin is bound to intrinsic factor. Pancreatic insufficiency may lead to cobalamin deficiency. Lack of intrinsic factor is the commonest cause of cobalamin deficiency; very rarely, aberrant forms of intrinsic factor are produced, but the clinical syndrome is similar. Gram-negative anaerobe bacteria bind the cobalamin-intrinsic factor complex, and bacterial overgrowth of the small intestine diminishes cobalamin resorption. Parasitic infections with fish tape-worm and Giardia lamblia are also associated with cobalamin malabsorption. The cobalamin-intrinsic factor complex binds to the ileal receptors in the terminal ileum. Cobalamin absorption may be impaired after resection or by diseases affecting more than 50 cm of the terminal ileum, such as Crohn's disease, coeliac disease, tuberculosis, lymphoma or radiation. There is clearly a wide diversity in the aetiology of cobalamin deficiency, which requires a versatile diagnostic approach.
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PMID:Intrinsic factor secretion and cobalamin absorption. Physiology and pathophysiology in the gastrointestinal tract. 177 33

Omeprazole is the first H+-K+-adenosine triphosphatase antagonist available for clinical use. It has a very strong, long-lasting inhibitory effect on gastric acid secretion. The effect is very selective: pepsin and intrinsic factor secretion are unaffected. Once-daily doses of 30-40 mg cause a more than 95% reduction of intragastric acidity. Lower doses have less predictable results. During treatment with omeprazole serum gastrin levels increase. After cessation of treatment gastric acid secretion and serum gastrin levels rapidly return to pretreatment levels. No rebound phenomena are observed after treatment.
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PMID:Effects of omeprazole on gastric secretory functions. 269 7

Rat intestinal microvillus membrane contains at least 24 polypeptides, of which 18 can be solubilized using Triton X-114 at 4 degrees C. Upon phase separation at 32 degrees C, 11 proteins separated nearly completely into the detergent-rich phase, while 9 proteins were found exclusively in the aqueous phase. Enzymes which were uniquely included in the detergent phase were alkaline phosphatase, leucine aminopeptidase, gamma-glutamyl transpeptidase, and Ca2+-Mg2+ ATPase. The proteins which were excluded from the detergent phase and found exclusively in the aqueous phase included the disaccharidases (glucoamylase, sucrase-isomaltase, trehalase, lactase) and the ileal receptor for the intrinsic factor-cobalamin complex. Integral membrane proteins can thus be separated during solubilization into two groups prior to further purification or characterization.
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PMID:Phase separation of rat intestinal brush border membrane proteins using Triton X-114. 301 Jul 62

The effect of gastric anacidity on the absorption of food-bound cobalamins is uncertain. Omeprazole, an inhibitor of the enzyme H-K-ATPase in the parietal cell, is the most potent inhibitor of gastric acidity known so far. In 17 healthy male volunteers the absorption of liver-bound cobalamins was assessed after a single intravenous dose of omeprazole (80 mg) or placebo in a double-blind, crossover manner. The effect of omeprazole on pH, gastric acidity, and intrinsic factor (IF) concentration was measured in aspirates of gastric juice 5 min before and 30 and 60 min after the administration of liver homogenate containing 0.74 nmol of 57Co-labelled cobalamins. Omeprazole treatment resulted in anacidity (pH values above 6.0) in 14 individuals 30 min after the liver dose and in 15 individuals after 60 min. The IF concentration was unchanged in the omeprazole experiment as compared with the placebo experiment. The absorption of liver-bound cobalamins was 310 pmol (189-501 pmol) in the omeprazole experiment as compared with 415 pmol (150-549 pmol) in the placebo experiment (median values and range, p = 0.5228). We suggest that anacidity induced by omeprazole does not reduce the absorption of liver-bound cobalamins.
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PMID:The effect of omeprazole on gastric acidity and the absorption of liver cobalamins. 357 26

Gastric units in the glandular epithelium of the mouse stomach contain several types of continuously renewing epithelial cells. Acid-producing parietal cells are derived from a multipotent stem cell that also gives rise to mucus-producing pit cells and pepsinogen- and intrinsic factor-producing zymogenic cells. We used nucleotides -1035 to +24 of the mouse H+/K(+)-ATPase beta subunit gene (H+/K(+)-ATPase beta subunit-1035 to +24) to examine the consequences of expressing simian virus 40 T antigen (SV 40 TAg) in the normally rare, nonproliferating, short-lived pre-parietal cell progenitor. Light and electron microscopic morphologic studies plus multilabel immunohistochemical analyses of postnatal day (P) 14-80-day transgenic mice revealed that SV40 TAg produces a 50-70-fold amplification of pre-parietal cells which become the predominant cell type in gastric units. Differentiation to mature parietal cells is blocked, resulting in hypochlorhydria and an associated systemic iron deficiency. SV40 TAg-induced pre-parietal proliferation is accompanied by apoptosis. Examination of adult transgenic mice homozygous for p53 wild type or p53 null alleles established that the apoptosis occurs through a p53-independent pathway. H+/K(+)-ATPase beta subunit -1035 to +24/SV40 Tag is not expressed during differentiation of the zymogenic lineage. Nonetheless, P28-P80 transgenic mice exhibit an apparent block in the conversion of pre-zymogenic to zymogenic cells. This block appears to be quite specific: conversion of preneck to neck cells and neck to pre-zymogenic cells is not affected. Comparison of normal and transgenic mice that are p53+/+ or p53-/- confirmed that the loss of mature zymogenic cells is not dependent upon p53. Although H+/K(+)-ATPase beta subunit -1035 to +24 is not active in pit cell progenitors or their differentiated descendants, there is a 2-3-fold increase in mature pit cells in transgenic animals. Our findings (i) demonstrate an approach for amplifying and characterizing pre-parietal or other progenitor cell populations in gastric units, (ii) reveal an SV40 TAg-inducible, p53-independent apoptotic mechanism that operates in a committed epithelial progenitor cell, and (iii) provide a transgenic mouse model for defining factors that may mediate progression through specific points in the differentiation programs of the parietal and zymogenic cell lineages or that may influence decisions about allocation to the pit cell lineage.
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PMID:Simian virus 40 T antigen-induced amplification of pre-parietal cells in transgenic mice. Effects on other gastric epithelial cell lineages and evidence for a p53-independent apoptotic mechanism that operates in a committed progenitor. 779 80

Previous studies on the distribution of parietal cells and G cells in normal adult stomachs have shown that in about 20% of specimens parietal cells extended to the pylorus. This study aimed to examine the distribution of parietal cells and G cells in the body and antrum of the developing human stomach in relation to anatomical landmarks, using histological and immunocytochemical methods. In all 15 fetal stomachs examined, parietal cells extended to the pylorus and expressed intrinsic factor and hydrogen-potassium-ATPase activity from week 13 of gestation. By contrast, in only one of the five infant stomachs did parietal cells extend to the pylorus: this is identical to the distribution in the adult. G cells developed in the antrum from 18 weeks' gestation and their distribution did not differ between the fetal and infant stomachs. These findings indicate that parietal cells disappear from the antrum of the stomach in the third trimester of pregnancy, but this process fails to occur in approximately 20% of the population.
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PMID:Immunocytochemical localisation of parietal cells and G cells in the developing human stomach. 817 53

The mechanisms that regulate cell lineage-specific and differentiation-dependent patterns of gene expression in the gastric units of the stomach are largely unknown. Transgenic mice were generated in order to identify cis-acting sequences that determine the zymogenic cell-specific pattern of expression of the mouse intrinsic factor (InF) gene and the parietal cell-specific pattern of expression of the mouse H+/K(+)-ATPase beta-subunit gene. Portions of the 5'-nontranscribed domains of each gene were linked to the human growth hormone (hGH) gene beginning at its nucleotide +3. RNA blot hybridization studies combined with multilabel immunocytochemical surveys using a panel of lineage-specific antibodies and lectins indicated that nucleotides -1035 to +24 of the mouse H+/K(+)-ATPase beta-subunit gene direct a pattern of reporter production which recapitulates the parietal cell-specific and developmental patterns of expression of the endogenous gene. Analysis of three mosaic founders containing H+/K(+)-ATPase beta-subunit-1035 to +24/hGH+3 revealed that they had monophenotypic gastric units: a given unit contained either a wholly hGH-positive or a wholly hGH-negative population of parietal cells. These latter findings provide very strong evidence that gastric units are monoclonal, i.e. they are supplied by stem cells having one genotype. Although some, but not all, parietal cells are apparently derived from the same committed progenitor as zymogenic cells, virtually all parietal cells in a given gastric unit, but none of its zymogenic cells, express InF-1029 to +55/hGH+3. This suggests that InF-1029 to +55 may contain cis-acting sequences which allow parietal cell expression in other species (e.g. humans) but lack additional elements which normally function in mice to suppress InF expression in this lineage. The absence of hGH in zymogenic cells also means that the transcriptional regulatory environments of parietal and zymogenic cells derived from the same precursor are distinguishable by InF-1029 to +55. H+/K(+)-ATPase beta-subunit-1035 to +24 and InF-1029 to +55 are the only two sequences reported to date that are able to direct foreign gene expression exclusively to a gastric epithelial cell lineage in transgenic mice. This ability to deliver gene products to parietal cells can now be exploited to identify factors that control their normal proliferation and differentiation programs and/or to specifically alter their biological properties.
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PMID:Use of transgenic mice to study regulation of gene expression in the parietal cell lineage of gastric units. 825 86

Little data exist regarding the activity of gastric parietal and G cells in the very immature infant. Therefore, we have examined the developing human stomach for the presence and location of parietal and G cells, by using both standard histological methods and antibodies to the H+/K(+)-ATPase (proton pump), intrinsic factor and gastrin in 25 fetuses (ranging from 13-28 weeks) and in 5 infants (2-21 weeks). Parietal cell activity was noted in the body, antrum and pyloric regions in all the fetal specimens examined. However, this activity was much more limited in the infant specimens. Gastrin immunoreactivity was noted in all specimens from 18 weeks of gestation onwards; this activity was located solely in the antral and pyloric region. These results indicate that the human fetus has the potential to produce gastric acid, intrinsic factor and gastrin from the middle of the second trimester.
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PMID:When is the fetus first capable of gastric acid, intrinsic factor and gastrin secretion? 832 94


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