Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostaglandins have been shown to prevent the damage to the gastric and intestinal mucosa which has been induced by diverse necrotizing substances. These damaging stimuli increase the liberation of histamine from mast cells. Because of its well known effects on cellular permeability, histamine may serve the initial stimulus for mediating cellular damage. The aim of our study was to investigate the effect of misoprostol, a synthetic PGE1 analog, on tissue histamine concentration and mast cell counts after damage to the gastric mucosa induced by stress, histamine, aspirin and concentrated ethanol in guinea pigs. Misoprostol or its matching placebo were administered intragastrically 3 minutes prior to the ulcerogenic stimulus. After the induction of the injury, the animals were sacrificed, stomachs were examined for ulceration. Gastric and duodenal histamine concentrations were determined. Mast cells from these organs were stained and counted. All four ulcerogenic stimuli resulted in significant gastric ulcer formation. This ulcerogenic action was accompanied by a significant decrease in mucosal histamine concentration and mast cell counts. Misoprostol induced a dose-dependent inhibition of gastric damage, histamine depletion and mast cell destruction. These results indicate that the stabilization of mast cells by misoprostol is an important mechanism for its mucosal protective effects against ulcerogens.
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PMID:Misoprostol prevents damage to the gastric mucosa by stabilizing the mast cells. 244 10

It is believed that aspirin (ASA) and other nonsteroidal antiinflammatory drugs elicit dysponea in ASA sensitive asthmatics by blocking the cyclooxygenase. It is unclear whether this bronchospasm is due to shunting of arachidonic acid into the lipooxygenase pathway or removal of cyclooxygenase product which prevent bronchospasm. Diminished tissue concentration of PGE may cause bronchoconstriction. PGE play also modulatory function to mast call decreasing the release of mediators of anaphylaxis. There are some evidences concerning the mast cell degranulation in postaspirin reaction in ASA sensitive asthmatics. The authors investigated the influence of synthetic analogue of PGE1--misoprostol (Cototec, Searle) on the postaspirin bronchoconstriction in seven ASA sensitive asthmatics aged 33-62. Aspirin threshold doses ranged from 10 to 150 mg. Postaspirin bronchoconstriction begun usually within 1-2 hrs after digestion of ASA and 200 micrograms were additionally given 2 h later. Seven days later misoprostol (400 micrograms) was administered together with previously determined dose of ASA. One the other day the bronchodilating effect of misoprostol alone was examined. In all but one patients we observed the protective influence of misoprostol on ASA induced bronchoconstriction. Max. fall in FEV1 in % after ASA in each of the patients was 40, 25, 24, 33, 47 and 54, and after ASA with misoprostol, respectively 10, 9, 4, (+8), 10, (+2) and 45. Misoprostol given together with ASA attenuated aspirin-induced bronchoconstriction reaching statistical significance at 3 and 3.5 h, and also diminished extrapulmonary symptoms. The authors discuss the possible mechanism of protective influence of misoprostol.
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PMID:[The influence of misoprostol on post-aspirin bronchoconstriction in patients with aspirin sensitive asthma]. 862 Jan 77

Misoprostol was found to be an extremely potent inhibitor of immunologically induced histamine release from mast cells isolated from both the human colonic mucosa and submucosa/muscle. The dose-inhibition curves were bell shaped, with IC(50) values in the range 0.1--1 nM. The compound was relatively selective for these cell types. It was less active against rat peritoneal mast cells, which again exhibited a bell-shaped dose-inhibition curve, but with a maximal inhibition of only about 30%, and human basophil leucocytes, where the inhibition was progressive with an IC(50) of similar1 &mgr;M. Very high concentrations of misoprostol (greater-than-or-equal5 &mgr;M) induced histamine release from all of the cell types examined. Insofar as the colonic mast cells may represent the two human mast cell phenotypes so far identified (MC(T) and MC(TC)), these data suggest that the drug may have therapeutic applications in human allergic and inflammatory diseases in which these cells are involved.
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PMID:Effect of Misoprostol on Histamine Secretion from Isolated Rat and Human Mast Cells and Basophils. 1185 84