Pharmacology of gastric acid inhibition

Shamburek, Robert D.; Schubert, Mitchell L.

doi:10.1016/0950-3528(93)90030-v

Cited by 36 publications

(15 citation statements)

References 151 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In parietal cells of the gastric mucosa, histamine via the H 2 R stimulates the production of protons (Hersey and Sachs, 1995). Although histamine is only one of several mediators exhibiting this function, its physiologic relevance is demonstrated by pharmacologic studies using selective antagonists (Shamburek and Schubert, 1993). Mice lacking the H 2 R were generated in 2000 (Kobayashi et al, 2000) and were found to have a normal gastric pH, indicating a compensation of the permanently absent H 2 R function by muscarinic M1 receptors, which may also point to problems associated with chronic therapy with H 2 R antagonists (Kobayashi et al, 2000).…”

Section: Hdcmentioning

confidence: 99%

Analysis of Histamine Receptor Knockout Mice in Models of Inflammation

Neumann

Schneider

Seifert

2013

J Pharmacol Exp Ther

View full text Add to dashboard Cite

The diverse functions of histamine are mediated by four specific histamine receptor subtypes, which belong to the family of Gprotein-coupled receptors. Here, we summarize data obtained with histamine-deficient L-histidine decarboxylase knockout and histamine receptor subtype knockout mice in inflammation models. Advantages and disadvantages of the knockout approaches compared with pharmacologic approaches are discussed critically. Due to many controversial data it is very difficult to draw clear-cut conclusions from the data provided in the literature.

show abstract

Section: Hdcmentioning

confidence: 99%

Analysis of Histamine Receptor Knockout Mice in Models of Inflammation

Neumann

Schneider

Seifert

2013

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…1). The increase in gastric acidity is considered an important contributing factor in the pathogenesis of gastric and duodenal ulcers and is often termed the 'aggressive factor' [36], The regulation of gastric acid secretions is complex and complicated; en dogenous gastrin, histamine, somatostatin and choliner gic mechanisms play major roles in controling gastric secretions [37], All these pathways converge on and mod ulate the activity of the proton pump of the parietal cells [38] . For acid secretion the expulsion of H+ across the api cal membrane is coupled with the movement of K+ into the cell [37], Furthermore basolatcral Na+-H+ exchange may also be a necessary accompaniment of acid secretion [39] Pretreatment with quinacrine significantly protected rats against indomethacin-induced gastric ulcers (table 2).…”

Section: Discussionmentioning

confidence: 99%

Effect of Quinacrine, a Phospholipase A<sub>2</sub> Inhibitor on Stress and Chemically Induced Gastroduodenal Ulcers

Moutaery

Tariq²

1997

Digestion

View full text Add to dashboard Cite

Quinacrine, a phospholipase A₂ inhibitor, has been studied for its ability to inhibit gastric secretion and to protect the gastric and duodenal mucosa against chemically and stress-induced ulcers. Acid secretion studies were undertaken in pylorus-ligated rats with and without quinacrine treatment. Experimental gastric lesions were induced by water-immersion restraint stress, indomethacin and 80% ethanol in rats; whereas duodenal ulcers were produced by treatment of rats with cysteamine. The level of nonprotein sulfhydryl compounds and gastric wall mucus were also measured in the glandular stomach of the rats following ethanol-induced gastric lesions. The results of this study demonstrate that quinacrine produces a dose-dependent inhibition of gastric acid secretion in rats. Pretreatment with quinacrine significantly attenuated the formation of stress-, indomethacin- and ethanol-induced gastric lesions. Quinacrine also protected intestinal mucosa against cysteamine-induced duodenal ulcers. The antiulcer activity of quinacrine was associated with appreciable inhibition of ethanol-induced depletion of nonprotein sulfhydryls and gastric wall mucus. These findings point towards the mediation of sulfhydryls in quinacrine-induced gastrointestinal cytoprotection. In conclusion, this study demonstrates that quinacrine possesses significant antiulcer and cytoprotective activity against various experimentally induced gastroduodenal lesions. Although the mechanism of action of quinacrine requires further evaluation, the experimental observations derived from this study may have future clinical relevance and therefore deserve to be investigated thoroughly.

show abstract

“…For each hydrogen ion secreted across the secretory membrane, one bicarbonate ion is generated in the cytoplasm and is transported across the basolateral membrane in exchange for chloride (Helander & Keeling 1993;Sachs et al 1990;Shamburek & Schubert 1993).…”

Section: Pharmacologymentioning

confidence: 99%

Risk-Benefit Assessment of Omeprazole in the Treatment of Gastrointestinal Disorders

Creutzfeldt

1994

Drug Safety

View full text Add to dashboard Cite

For the treatment of duodenal and gastric ulcer and reflux oesophagitis, especially erosive oesophagitis, omeprazole has an advantage over histamine H2-receptor antagonists because it heals significantly more patients significantly faster. Adverse effects have been observed during short term treatment with the same frequency as during treatment with H2-antagonists. Also, maintenance treatment with omeprazole of reflux oesophagitis is significantly superior to H2-antagonist therapy. During long term treatment for up to 8 years no further drug-related adverse effects have been observed. Moderate hypergastrinaemia occurs in some patients, especially if an omeprazole dosage of 40 mg/day is needed. A slight increase of the agyrophil (endocrine) cell volume density and an extension of micronodular hyperplasia in the oxyntic mucosa after several years of omeprazole treatment seem to be related to the severity of the corpus gastritis and not to drug-induced hypergastrinaemia, because similar changes have been observed in equal frequency in patients not receiving anti-secretory drugs. Theoretical arguments against long term treatment with potent acid-suppressing drugs, such as the possible consequences of gastric bacterial overgrowth or hypergastrinaemia, are not supported by clinical observations and epidemiological data and are, therefore, speculative.

show abstract

Pharmacology of gastric acid inhibition

Cited by 36 publications

References 151 publications

Analysis of Histamine Receptor Knockout Mice in Models of Inflammation

Analysis of Histamine Receptor Knockout Mice in Models of Inflammation

Effect of Quinacrine, a Phospholipase A<sub>2</sub> Inhibitor on Stress and Chemically Induced Gastroduodenal Ulcers

Risk-Benefit Assessment of Omeprazole in the Treatment of Gastrointestinal Disorders

Contact Info

Product

Resources

About