Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A membrane fraction containing H,K-ATPase (EC 3.6.1.36) was prepared from pig gastric mucosa and found to contain phospholipase A2 (EC 3.1.1.4) and lysophospholipase (EC 3.1.1.5) activities. Washing the membranes decreased their protein content by 25%. Recovery profiles of H,K-ATPase, phospholipase A2 and lysophospholipase were similar for membranes washed either with water or with 0.15 or 1.5 M KCl. Nearly identical distribution profiles were obtained for the three enzyme activities after centrifugation of washed vesicle membranes on a linear sucrose gradient. The phospholipase A2 activity was stimulated by calcium and increased further in the presence of calmodulin. The amount of cellular radioactively labelled lysophosphatidylcholine was doubled upon cholinergic stimulation of isolated parietal cells prelabelled with [3H]glycerol or 32Pi. The liberated lyso[32P]phosphatidylcholine had its acyl chain in the sn-1 position, which implies an activation of a phospholipase A2. These findings indicate that secretagogues which increase the cytosolic Ca2+ concentration, i.e. acetylcholine, histamine and gastrin, may activate a phospholipase A2 in the parietal cell.
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PMID:Occurrence of phospholipase A2 and lysophospholipase in a gastric H,K-ATPase-containing membrane fraction, and the formation of lysophosphatidylcholine in stimulated pig parietal cells. 196 31

Infection with Helicobacter pylori (H. pylori) is now recognized as a major factor in the pathogenesis of gastric disease, and the successful therapy regimens require a combination of H2 blockers with gastroprotective and antimicrobial agents. Ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene) amino]-4-thiazolyl] methyl]thio]ethyl]amino]methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542) is the only drug combining acid-suppressant activity with remarkable gastroprotective and anti-H. pylori properties. The drug not only displays a potent anti-H. pylori activity alone, but also exerts a strong potentiating effect on the efficacy of antimicrobial agents commonly used for H. pylori eradication, and the successful ulcer therapy with ebrotidine induces a significant (4-fold) increase in the H. pylori aggregation titer of gastric mucin. Moreover, the drug exhibits a strong inhibitory effect on H. pylori urease activity, the extent of which exceeds that of ranitidine, omeprazole and lansoprazole. Ebrotidine has also been demonstrated to exert a potent inhibitory action on the enzymatic activities directed towards mucus perimeter of gastric mucosal defense, causing a marked inhibition of H. pylori protease, lipase and phospholipase A2 activities. Another important property of ebrotidine is its ability to efficiently counteract the disruptive effects of H. pylori lipopolysaccharide on the integrity of gastric epithelium. This includes countering the interference by the lipopolysaccharide in mucosal integrin receptor interaction with proteins of extracellular matrix and the reversal of H. pylori disruptive effect on the binding of mucin to its gastric epithelial receptor. Furthermore, most recent data indicate that ebrotidine has the ability to reverse the impairment caused by H. pylori in feedback inhibition of gastrin release by somatostatin. This activity of ebrotidine apparently stems from the drug's ability to counter the untoward effect of H. pylori on the binding of somatostatin to its specific receptor on the gastric mucosal G-cells. The unique combination of acid suppressant, gastroprotective and anti-H. pylori activities makes ebrotidine a drug of choice in the treatment of gastric disease caused by H. pylori.
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PMID:Anti-Helicobacter pylori activities of ebrotidine. A review of biochemical and animal experimental studies and data. 920 47

The ECL cells control parietal cells by releasing histamine in their immediate vicinity. Gastrin and pituitary adenylate cyclase-activating peptide (PACAP) stimulate histamine secretion from isolated ECL cells, while somatostatin and galanin inhibit stimulated secretion. Prostaglandin E2 and related prostaglandins likewise suppress ECL-cell histamine secretion. Conceivably, that is how they inhibit acid secretion. In the present study, we examined if prostaglandin E2 can be generated by isolated ECL cells. Rat stomach ECL cells were purified (>90% purity) by counterflow elutriation and gradient centrifugation and cultured for 48 h. ECL cell stimulants (gastrin and PACAP) and inflammatory agents (interleukin-1 beta, tumor necrosis factor-alpha and bradykinin) were tested for their ability to induce prostaglandin E2 accumulation (24-h incubation), measured by radioimmunoassay. Gastrin and PACAP did not affect prostaglandin E2 accumulation but interleukin-1 beta (300 pg/ml), tumor necrosis factor-alpha (10 ng/ml) and bradykinin (1 microM) induced a 2- to 3-fold increase in the amount of prostaglandin E2 accumulated. While the combination of interleukin-1 beta and bradykinin induced a 9-fold increase, the combination interleukin-1 beta+tumor necrosis factor-alpha and bradykinin + tumor necrosis factor-alpha induced additive effects only. The combination of interleukin-1 beta + tumor necrosis factor-alpha + bradykinin did not induce a greater effect than interleukin-1 beta + bradykinin. The effect of interleukin-1 beta + bradykinin was abolished by adding 10 nM hydrocortisone (suppressing phospholipase A2 and cyclooxygenase) or 1 microM indomethacin (inhibiting cyclooxygenase). Incubating ECL cells in the presence of interleukin-1 beta+bradykinin for 24 h reduced their ability to secrete histamine in response to gastrin. The inhibitory effect was reversed by 1 microM indomethacin. Also, increasing the concentrations of hydrocortisone in the medium resulted in an enhanced gastrin-stimulated histamine secretion. Hence, the previously described acid-inhibiting effect of inflammatory agents may be explained by inhibition of ECL-cell histamine mobilization, consequent to enhanced formation of prostaglandin E2 by cells in the oxyntic mucosa, including the ECL cells themselves.
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PMID:Isolated rat stomach ECL cells generate prostaglandin E(2) in response to interleukin-1 beta, tumor necrosis factor-alpha and bradykinin. 1129 Mar 77