Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20020 (adenosine triphosphatase)
 3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antibodies to a membrane-bound antigen, localized to the canalicular structures of the parietal cell, are found in most sera of patients with chronic atrophic gastritis and pernicious anemia. In the present study immunoglobulins containing parietal cell antibodies were found to inhibit the activity of H+,K+-adenosine triphosphatase (EC 3.6.1.36) in a tubulovesicular membrane preparation from porcine gastric mucosa. The degree of inhibition correlated to the titer of parietal cell antibodies as assessed by an enzyme-linked immunosorbent assay. The specificity of the enzymatic inhibition was confirmed by the lack of effect of parietal cell antibodies on membrane-bound esterase. A possible interaction of parietal cell antibodies with gastrin binding at the receptor level was investigated in a radioreceptor assay employing 125I-gastrin 1 and gastric mucosal cell suspension from the guinea pig. No blocking capacity was found with immunoglobulins from patients with pernicious anemia as compared with immunoglobulins from healthy controls. The results thus demonstrate a direct inhibitory effect of parietal cell antibodies on the acid producing H+,K+-adenosine triphosphatase of the parietal cell, but also a lack of interaction with the gastrin receptor, and indicate that in the development of hypo/achylia H+,K+-adenosine triphosphatase autoantibodies could have a major pathogenic role.
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PMID:Parietal cell antibodies in pernicious anemia inhibit H+, K+-adenosine triphosphatase, the proton pump of the stomach. 254 Oct 40

We studied whether enprostil, a synthetic prostaglandin E2 derivative, might inhibit gastrin release and the trophic effects on gastric oxyntic mucosa induced by prolonged treatment with an inhibitor of hydrogen-potassium-stimulated adenosine triphosphatase, the substituted benzimidazole BY 831-78. Rats were treated intragastrically with enprostil (1 or 15 micrograms/kg b.i.d.), BY 831-78 (15 mumol/kg once daily), the combination of enprostil and BY 831-78, ranitidine (300 mumol/kg b.i.d.), and placebo. Plasma gastrin and somatostatin levels and gastric acid secretion were measured during a 1-day treatment in animals fitted with chronic gastric fistulas and repeatedly during 9 wk of treatment in intact rats. Despite inhibiting acid secretion, enprostil did not increase plasma gastrin. When combined with BY 831-78, enprostil transiently reduced the BY 831-78-induced increase of integrated plasma gastrin (1375 +/- 206 vs. 2137 +/- 256 pmol/L.12 h, p less than 0.05) in fasted rats with fistulas, but failed to prevent the marked hypergastrinemia following 9 wk of treatment with BY 831-78 (717 +/- 80 vs. 731 +/- 56 pmol/L) in intact rats. However, enprostil reduced the BY 831-78-induced increase of oxyntic mucosal volume (458 +/- 31 vs. 567 +/- 33 mm3, p less than 0.01), whereas BY 831-78 prevented the enprostil-induced increase of antral mucosal volume (42 +/- 3 vs. 56 +/- 3 mm3, p less than 0.01). These results demonstrate that some of the trophic effects induced by a hydrogen-potassium-stimulated adenosine triphosphatase inhibitor are not exclusively governed by gastrin.
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PMID:Enprostil reduces the increase of gastric corpus mucosal mass induced by the hydrogen-potassium-stimulated adenosine triphosphatase inhibitor BY 831-78 in the rat. 257 Jul 29

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

Due to its potent and long-lasting antisecretory properties is omeprazole, the first clinically used H+/K+-adenosine triphosphatase inhibitor, highly effective in healing of duodenal and gastric ulcers and reflux oesophagitis. Omeprazole is superior to all other presently available antiulcer drugs in the treatment of Zollinger-Ellison syndrome and refractory ulcers. Short-term administration of the drug is safe. However, serum gastrin and gastric enterochromaffin-like cells should be carefully monitored during long-term treatment with the drug.
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PMID:H+/K+-adenosine triphosphatase inhibitors. A new approach to the treatment of acid-peptic diseases. 269 16

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of omeprazole are reviewed. Omeprazole, a substituted benzimidazole, has a unique site and mechanism of action because it inhibits the proton pump--i.e., hydrogen, potassium adenosine triphosphatase (H+,K+-ATPase)--and consequently blocks the final common step in the gastric acid secretory pathway. Omeprazole inhibits basal and histamine-, gastrin- and pentagastrin-stimulated gastric hydrochloric acid secretion. It produces a dose-dependent reduction in gastric acidity, gastric acid output, and gastric juice volume and has variable effects on pepsin secretion. Omeprazole has no documented effect on esophageal motility or lower esophageal sphincter pressure. Omeprazole is variably absorbed from the gastrointestinal tract, and food appears to decrease the rate, but not the extent, of drug absorption. The drug is approximately 95% bound to plasma proteins and is metabolized to inactive components that are enterohepatically or renally eliminated. Omeprazole is more effective (in most studies) than H2-receptor antagonists in treating duodenal ulcer, at least as effective in treating benign gastric ulcer, and more effective in treating reflux esophagitis. Omeprazole has been used successfully in patients with Zollinger-Ellison syndrome refractory to treatment with H2-receptor antagonists. Gastrointestinal complaints (nausea and diarrhea) are the most commonly reported adverse effects associated with omeprazole therapy. The most frequently reported laboratory abnormality occurring with omeprazole use is elevation of serum aspartate aminotransferase and alanine aminotransferase concentrations. Omeprazole will serve a valuable role in the management of gastrointestinal tract ulcers and hypersecretory conditions.
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PMID:Therapeutic evaluation of omeprazole. 306 85

Rabeprazole, a new benzimidazole proton pump inhibitor (PPI), is among a class of agents known to be very potent inhibitors of gastric acid secretion. PPIs inhibit hydrogen-potassium adenosine triphosphatase activity on the luminal surface of the parietal cell, effectively blocking the final common pathway for gastric acid secretion. Raising gastric pH stimulates the production of gastrin by G cells in the antrum of the stomach, which can lead to enterochromaffin-like (ECL)-cell hyperplasia. In the past, these changes have been viewed with concern, particularly in the light of studies in rats indicating that hypergastrinaemia and ECL-cell hyperplasia induce gastric carcinoid tumour formation. All available clinical data indicate that long-term PPI use does not lead to carcinoid tumour formation in humans. In fact, both serum gastrin elevation and ECL-cell hyperplasia are now generally viewed as normal physiological responses to gastric acid suppression. Serum gastrin concentrations, in particular, correlate well with gastric acid suppression, which has led to the use of gastrin response by some investigators as a surrogate marker of antisecretory effectiveness. Long-term tolerability data indicate that PPIs have a favourable side-effect profile. Data obtained from patients receiving acute or long-term maintenance rabeprazole therapy support this conclusion. Furthermore, neither animal nor human data obtained with rabeprazole suggest a significant risk for neoplastic changes secondary to hypergastrinaemia.
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PMID:Review article: current perspectives on hypergastrinaemia and enterochromaffin-like-cell hyperplasia. 1055 3

To study in vivo the cellular differentiation and secretion of human developing fetal stomach, ethically and technically impossible to perform in utero, 256 fetal stomachs were xenografted. Human stomachs from 6- to 10-week-old fetuses were grafted for 1-273 days into nude mice. Biopsies for immunohistochemistry, hybridization and electron microscopy were taken and a catheter introduced into the human stomach. Macroscopic growth was fast and cells in S phase were numerous during the first 9 weeks, then the stomach size was stable and the gastric mucosa, of adult type, remained normal. In situ hybridization detected only a minute mouse mesenchymal chimerism in the graft. Chromogranin A, intrinsic factor and H+/K+ adenosine triphosphatase were immunohistolocally detected in epithelial cells 20 days after grafting, gastrin was detected after 30 days and pepsinogen after 60 days. The pH in gastric juice, which was at 8.0 +/- 0.1 from days 10-25, dropped from 4.39 +/- 1.80 at 30 days to 1.58 +/- 0.29 at 90 days. Intrinsic factor was stable and pepsin ranged from 6.8 +/- 7.8 to 134 +/- 51 units at 90 days. The differentiation of the epithelial cells in xenografts was very accelerated in comparison to that in utero.
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PMID:Morphologic and functional development of whole human fetal stomachs grafted into nude mice. 1147 49

The more potent and longer-lasting inhibition of gastric acid secretion provided by proton pump inhibitors (PPIs) as compared with histamine-2-receptor antagonists is caused in large part by differences in their mechanism of action. PPIs block histamine-2-, gastrin-, and cholinergic-mediated sources of acid production and inhibit gastric secretion at the final common pathway of the H+/K+ adenosine triphosphatase proton pump. In contrast, histamine-2-receptor antagonists cannot block receptor sites other than those mediated by histamine. It seems that the rapid loss of acid suppression activity by the histamine-2-receptor antagonists may be attributed to tolerance. Such tolerance has not occurred in patients receiving PPIs because these agents are irreversible inhibitors of the H+/K+ adenosine triphosphatase proton pump. For these reasons, patients who have acid-related disorders that require high levels of acid suppression do not respond well to intravenous histamine-2-receptor antagonists and would be excellent candidates for intravenous PPI therapy. Candidates for intravenous PPIs also include patients who cannot receive oral PPIs and those who may need the higher acid suppression therapy provided by the intravenous rather than the oral route. Clinical studies have demonstrated the efficacy of intravenous pantoprazole in maintaining adequate control of gastric acid output during the switch from oral to intravenous therapy in patients with severe gastroesophageal reflux disease or the Zollinger-Ellison syndrome. Intragastric administration of solutions prepared from oral PPIs has been used as an alternative to the intravenous route in critical care settings. However, decreased bioavailability may limit the value of intragastric delivery of PPIs because of the high frequency of gastric emptying problems in critically ill patients.
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PMID:Pharmacology of acid suppression in the hospital setting: focus on proton pump inhibition. 1207 61

Amidated and nonamidated progastrin-derived peptides have distinct biological activities that are mediated by a range of receptor subtypes. The objective was to determine the nature of the stored and secreted progastrin-derived peptides and to investigate whether progastrin release is regulated by gastric acidity. Using an antiserum directed to the C terminus of progastrin for identification and to monitor purification, C-terminal flanking peptides (CTFP) of progastrin (prog(76-83), prog(77-83), and prog(78-83) in approximately equivalent amounts) were isolated and identified from extracts of sheep antrum using ion exchange, HPLC, and mass spectrometry. Only trace amounts of full-length progastrin were present. Progastrin CTFP was the predominant progastrin-derived peptide in the antrum [progastrin CTFP/gastrin amide (Gamide) = 3]. Similarly, progastrin CTFP was the major circulating form in the antral (CTFP, 710 +/- 62 pmol/liter; Gamide, 211 +/- 35 pmol/liter) and jugular (CTFP, 308 +/- 16 pmol/liter; gastrin amide, 32 +/- 3 pmol/liter) veins. Alteration of gastric acidity in sheep by iv infusion of a H/K-adenosine triphosphatase inhibitor or somatostatin or by intragastric infusion of HCl demonstrated that the CTFP concentrations changed, although to a lesser extent than the changes in circulating gastrin amide. We conclude that the CTFP of progastrin is the major stored and circulating species of the gastrin gene, and that it is secreted in a regulated fashion rather than constitutively. Because full-length progastrin is bioactive, but is only a minor antral and secreted form, determination of the biological activity of the C-terminal flanking peptides will be important for a complete understanding of gastrin endocrinology.
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PMID:Identity and regulation of stored and secreted progastrin-derived peptides in sheep. 1530 16

Methyl eugenol induces neuroendocrine (NE) cell hyperplasia and tumors in F344/N rat stomach. Detailed histopathological and immunohistochemical (IHC) characterization of these tumors has not been previously reported. The objective of this study was to fill that data gap. Archived slides and paraffin blocks were retrieved from the National Toxicology Program Archives. NE hyperplasias and tumors were stained with chromogranin A, synaptophysin, amylase, gastrin, H(+)/K(+) adenosine triphosphatase (ATPase), pepsinogen, somatostatin, and cytokeratin 18 (CK18) antibodies. Many of the rats had gastric mucosal atrophy, due to loss of chief and parietal cells. The hyperplasias and tumors were confined to fundic stomach, and females were more affected than the males. Hyperplasia of NE cells was not observed in the pyloric region. Approximately one-third of the females with malignant NE tumors had areas of pancreatic acinar differentiation. The rate of metastasis was 21%, with liver being the most common site of metastasis. Immunohistochemically, the hyperplasias and tumors stained consistently with chromogranin A and synaptophysin. Neoplastic cells were also positive for amylase and CK18 and negative for gastrin, somatostatin, H(+)/K(+) ATPase, and pepsinogen. Metastatic neoplasms histologically similar to the primary neoplasm stained positively for chromogranin A and synaptophysin. Based on the histopathological and IHC features, the neoplasms appear to arise from enterochromaffin-like cells.
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PMID:Histopathological and Immunohistochemical Characterization of Methyl Eugenol-induced Nonneoplastic and Neoplastic Neuroendocrine Cell Lesions in Glandular Stomach of Rats. 2545 33


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