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)

The antiulcerogenic effect of zinc acexamate on gastric ulcers induced by reserpine and changes in the morphology of gastric mucosa were studied in rats by histochemical methods. Histochemistry revealed that zinc acexamate preserved reserpine-depleted neutral and acid glycoproteins. ATPase reaction remained strong in nearly normal periglandular capillaries. The reaction intensity of SDH and NADH2-tetrazolium reductase, and the number and size of the DH-positive parietal cells were decreased, illustrating the decline of energy metabolism involved in acid secretion. The decreased height and weaker staining of the pyroninophile chief cell layer corresponded to the lower amount of RNA, an indirect indicator of pepsinogen synthesis. The significant correlation indices "r" between the severity of gastric lesions and histochemical parameters of the defensive (glycoproteins and microvascular ATPase) and aggressive factors (parietal cell DH and chief cell RNA) confirmed the pathogenic effect of reserpine and the protection provided by zinc acexamate. These findings confirm the multifactorial mechanism of action described for zinc acexamate in several previous works.
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PMID:Protective effect of zinc acexamate on experimental gastric ulcers: a histochemical study. 128 67

The presence of autoimmune gastritis was investigated in 54 women with postpartum thyroiditis. Parietal cell antibodies (PCA) specific against H+, K(+)-adenosine triphosphatase (EC 3.6.1.36) were found in 18 women during pregnancy; in 10 of them, a 2-9-fold increase in the PCA level was observed in the postpartum period. At a 5-year follow-up, the initially PCA-positive women still had elevated antibody levels. Hypergastrinemia and low pepsinogen levels were noted in 4 women. In 2 of these women low serum vitamin B12 levels had developed. In 6 of 9 PCA-positive women examined by gastroscopy, biopsy specimens from the gastric body mucosa contained mononuclear cells, mainly T lymphocytes (CD3+) and macrophages (Leu-M3+) combined with an aberrant epithelial expression of HLA-DR. In four patients with chronic gastritis, all parietal cells, as defined by a specific monoclonal antibody, were found to have immunoglobulin G (IgG) deposits by a double-immunostaining method. Three of them had microscopic evidence of atrophy, whereas in 1 patient the body mucosa was intact. In 1 further patient with intact glands at histological examination, the basolateral membrane of some oxyntic glands was coated with IgG. The selective in situ deposition of antibodies associated with histologically intact parietal cells may support the concept that specific autoantibodies participate in the early pathogenesis of parietal cell destruction.
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PMID:A study of autoimmune gastritis in the postpartum period and at a 5-year follow-up. 132

The occurrence of auto-antibodies in patients with the autoimmune disease pernicious anaemia and in patients with active duodenal ulcers was investigated. In order to characterize antigenic structures, various cellular and subcellular fractions were prepared from pig gastric mucosa and from a homogenate of duodenal mucosa. By means of an enzyme-linked immunosorbent assay and immunoblotting, both the H+,K(+)-ATPase and pepsinogen/pepsin were shown to constitute the major antigens. All of the seven pernicious-anaemia sera that were tested contained auto-antibodies against both antigens, and the epitopes of the H+,K(+)-ATPase were shown to be localized on its cytoplasmic face. In 75% (18/24) of the sera from patients with duodenal ulcers, auto-antibodies were detected when using purified antigens. Six sera reacted with H+,K(+)-ATPase and twelve reacted with pepsinogen, one reacted with both antigens, and four sera reacted with the duodenal mucosal antigen. The occurrence of auto-antibodies indicates that there is a mucosal lesion and that immunological factors may be involved in the pathogenesis of the disease in some patients.
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PMID:The occurrence of auto-antibodies in patients with gastro-duodenal lesions. 169 83

The rabbit gastric gland model was used to study the nature of the muscarinic cholinergic and gastrin responses of parietal cells. Carbachol (100 microM) stimulation of acid secretion, as measured by the accumulation of aminopyrine, was inhibited by the M1 antagonist pirenzepine with an IC50 of 13 microM; by the M2 antagonist 11,2-(diethylamino)methyl-1-piperidinyl acetyl-5,11-dihydro-6H-pyrido 2,3-b 1,4-benzodiazepin-6-one (AF-DX 116) with an IC50 of 110 microM; and by the M3 antagonist diphenylacetoxy-4-methylpiperidinemethiodide (4-DAMP) with an IC50 of 35nM. The three antagonists displayed similar IC50 values for the inhibition of carbachol-stimulated production of 14CO2 from radiolabeled glucose, which is a measure of the turnover of the H(+)-H(+)-ATPase. Intracellular calcium levels wer measured in gastric glands loaded with FURA2. Carbachol was shown both to release calcium from an intracellular pool and to promote calcium entry across the plasma membrane. The calcium entry was inhibitable by 20 microM La3+. The relative potency of the three muscarinic antagonists for inhibition of calcium entry was essentially the same as for inhibition of acid secretion or metabolism. However, the rise in cell calcium due to release of calcium from intracellular stores was inhibited by 4-DAMP with an IC50 of 1.7 nM. Image analysis confirmed that the effect of carbachol and of the antagonists on intracellular calcium was occurring in the partial cell. In particular, the high-affinity inhibition of calcium release by 4-DAMP occurs in the parietal cell. Accordingly, it appears that the secretory receptor of the parietal cell is of the M3 type, and acid secretion depends on the entry of calcium rather than on calcium release from intracellular stores. In parallel experiments gastrin (G-17-sulfated) produced a dose-dependent increase in intracellular calcium (EC50, 0.14 +/- 0.013 microM). No stimulation of acid secretion was observed, but pepsinogen secretion was stimulated dose-dependently (EC50 = 1.17 +/- 0.21 microM).
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PMID:Second messengers in the gastric gland: a focus on calcium. 204 37

Experimental studies performed on 227 rats showed that Zn-aspartate and Zn-glycinate administered ip lowered the incidence, number, and severity of the reserpine-induced gastric lesions ensuring significant protection indices. Histochemical methods revealed increased amount of mucosal glycoproteins. The activity of dehydrogenases involved in energy metabolism that modulates acid secretion in the parietal cells was depressed. RNA content in the chief cells, as premises of pepsinogen synthesis, was decreased. ATPase reaction in the periglandular capillaries was uniform and stronger, showing an improvement of gastric mucosal microcirculation. Since these histochemical changes were also noted in healthy rats receiving Zn salts, it might be suggested that they are not the mere expression of an anti-ulcer protective effect of zinc, but rather reflect its mechanism of action, relating to the complex metabolic events induced by the trace element. Our results are in agreement with those previously reported concerning the noxious influence of Zn depletion, the accelerated healing of peptic ulcer patients after Zn treatment, and the protective effect of Zn against ulcerogenesis in several experimental models involving different pathomechanisms.
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PMID:Effects of zinc-aspartate and zinc-glycinate in healthy rats and on reserpine-induced gastric lesions. 248 53

Using isolated cells and subcellular fractions from pig gastric mucosa, antigenic structures with specific binding of IgG from sera of patients with auto-immune atrophic gastritis were characterized by means of immunoblotting and enzyme-linked immunosorbent assay. In immunoblotting experiments using mucosal cells as the antigen source, two dominating bands of 94 and 41 kDa were found. The two major antigens were identified as the H,K-ATPase (94 kDa), which constitutes the parietal cell acid pump, and pepsinogen (41 kDa) located in the chief cells. There was also a small but significant binding of antibodies to a preparation of Na,K-ATPase, an enzyme which is about 60% homologous to H,K-ATPase. Commercial preparations of hog gastric pepsinogen and pepsin bound pernicious anaemia IgG with equal efficacy. When sera from seven patients with the diagnosis pernicious anaemia were tested, all were found to contain auto-antibodies against H,K-ATPase as well as pepsinogen. In intact, isolated H,K-ATPase-containing vesicles the cytosolic part of the ATPase molecule is facing the outside of the vesicles. Both intact and trypsinized vesicles were incubated with patient sera and with a monoclonal antibody against H,K-ATPase. Pernicious anaemia IgG was found to bind to a cytosolic, trypsin-resistant structure, but the binding of the monoclonal antibody was lost upon trypsinization. The present results indicate that intracellular structures of the gastric mucosa, due to cell damage, may be exposed to immune-competent cells, which do not recognize these structures as 'self'.
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PMID:Characterization of antigenic structures in auto-immune atrophic gastritis with pernicious anaemia. The parietal cell H,K-ATPase and the chief cell pepsinogen are the two major antigens. 252 90

The possible relationship between peptic ulcer and the occurrence of auto-antibodies was investigated by means of an enzyme-linked immunosorbent assay (ELISA). Sera from 24 patients with active duodenal ulcer were analysed using cells and subcellular fractions from pig gastric acid duodenal mucosa for binding of immunoglobulins. Four sera (17%) reacted with a homogenate from duodenal mucosa. Nine sera (38%) were found to contain auto-antibodies against gastric mucosal cells. The cell-reactive auto-antibodies were shown to bind preferentially to parietal cells and chief cells. In these cells the antigens were identified as H, K-ATPase and pepsinogen respectively. Six sera were positive against purified H,K-ATPase; 12 sera were positive against pepsinogen, and only one of these sera reacted with both H,K-ATPase and pepsinogen. The results show that auto-antibodies are formed in a large fraction of patients (18/24; 75%) with peptic ulcer disease. The present study further demonstrates that enrichment of antigenic structures is required for obtaining a satisfactory sensitivity in the assay.
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PMID:The occurrence of gastric and duodenal auto-antibodies in peptic ulcer disease. 253 48

Treatment of rats with cycloheximide 1 h before carbachol dose-dependently reduced the secretagogue-stimulated gastric acid secretion in pylorus ligated rats, and partially blocked carbachol- or histamine-induced activation of rat gastric (H+ + K+)-ATPase which includes translocation of reserve intracellular (H+ + K+)-ATPase into the apical membrane of the parietal cells and induction of a KCl pathway. Time-course studies showed that the drug was effective only when administered at least 30 min before the secretagogues. Puromycin showed the same effect as cycloheximide. Pulse labelling studies with [35S]methionine led to identification of two most actively synthesized polypeptides in rat gastric mucosa; the proteins of 38,000 and 14,000 molecular weight. The larger polypeptide was identified as rat pepsinogen. The identity of the smaller protein is not known yet. We suggest that synthesis of nascent polypeptide(s) is required for certain steps of the acid secretory process leading to the activation of the acid pump.
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PMID:Gastric antisecretory activity of cycloheximide due to inhibition of protein synthesis. 303 29

To investigate the involvement of guanosine 3',5'-cyclic monophosphate (cGMP) in the cholinergic activation of gastric acid and pepsinogen secretion, we studied the subcellular and cellular relation between particulate guanylate cyclase and muscarinic cholinergic receptor sites. Subcellular fractionation of homogenates from rabbit gastric glands showed that particulate guanylate cyclase and muscarinic receptors were distributed in similar patterns, which differed from the pattern found for Na+-K+-ATPase, a marker for basal-lateral plasma membranes. Assuming a basal-lateral membrane localization for particulate guanylate cyclase and cholinergic receptors, these results suggested a heterogeneity of glandular basal-lateral membranes. The distributions of these markers among fractions enriched in isolated canine parietal or chief cells were also followed. Na+-K+-ATPase correlated with parietal cell distribution (r = 0.86) and guanylate cyclase with chief cell distribution (r = 0.76). The distribution of quinuclidinyl benzilate (QNB) binding sites indicated association of muscarinic receptors with both cell types. The similar subcellular and cellular distributions of guanylate cyclase and QNB binding sites may reflect a functional relationship of these markers in muscarinic-activated pepsinogen secretion. As seen in most other tissues, gastric glandular guanylate cyclase was not stimulated by various gastric secretagogues. We found that small changes in Ca2+ concentration, within the micromolar range, can regulate glandular guanylate cyclase activity. These results are discussed in terms of the cholinergic activation of parietal and chief cell function.
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PMID:Muscarinic receptors and guanylate cyclase in mammalian gastric glandular cells. 614 Aug 59

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


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