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

Tryptase and chymase released from activated mast cells degrade the neuropeptides calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP) to peptide fragments. We have examined whether nedocromil sodium can modulate the ability of rat activated peritoneal mast cells to degrade 125I-CGRP and 125I-VIP. Mast cell-dependent degradation of both 125I-CGRP and 125I-VIP was observed with compound 48/80 (0.03-1 microgram/ml) and in the case of 125I-VIP with anti-IgE (1-20 micrograms/ml). Nedocromil sodium (10(-6)-10(-4) M) caused significant inhibition of neuropeptide degradation, with the most effective inhibition observed against anti-IgE-induced degradation of 125I-VIP. Nedocromil sodium had no inhibitory effect on the ability of lysed mast cells, bovine trypsin or chymotrypsin to breakdown 125I-VIP. These results suggest that nedocromil sodium inhibits mast cell-dependent degradation of neuropeptides, such as VIP, as a secondary consequence of inhibiting the release of mast cell proteases.
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PMID:The modulation by nedocromil sodium of proteases released from rat peritoneal mast cells capable of degrading vasoactive intestinal peptide and calcitonin gene-related peptide. 839 43

Many studies have demonstrated the ability of nedocromil sodium to block the acute response to allergen in persons who are sensitive to allergen. One study with subjects sensitive to ragweed showed a significant protective effect after a single 4 mg dose of nedocromil sodium, with no further protection achieved at higher doses. Numerous studies have also shown the ability of the drug to reduce or abolish the late asthmatic response in sensitive subjects when it was given before allergen challenge. Nedocromil sodium has also been shown to prevent the subsequent development of bronchial hyperresponsiveness. In addition, nedocromil sodium prevented the late asthmatic response when given after allergen challenge and an intact early response. These findings suggest that nedocromil sodium may be preventing the inflammatory events initiated by mast cell mediator and cytokine release.
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PMID:Clinical effects of nedocromil sodium on allergen-related mechanisms. 893 87

Ocular allergies are commonly encountered in clinical practice. The familiarity with the typical constellation of signs and symptoms, as well as the pathophysiology of these syndromes, is of utmost importance in diagnosing and treating these diseases. Several new therapeutic options have been tested in clinical settings in recent time. Lodoxamine tromethamine is a mast cell stabilizer at least as effective as cromolyn sodium, which is currently not available in the United States. Nedocromil sodium in addition to its mast cell stabilizing effect, has anti-inflammatory properties. Levocabastine hydrochloride is a very selective and potent H1 antihistamine. Ketorolac tromethamine is a topical nonsteroidal anti-inflammatory agent.
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PMID:Allergic and atopic diseases of the lid, conjunctiva, and cornea. 1015 Aug 78

Activation of mast cells, the key cells of allergic inflammation, causes typical morphological changes associated with an increase in volume, that is a function of area and perimeter. The purpose of this study was to evaluate the effect of mast cell activation to degranulate, carried out by the secretagogue Compound 48/80, and of inhibition of this activation carried out by Nedocromil sodium, a mast cell stabilizing drug, on mast cell area, perimeter and shape factor by a computerized image analyzer. Mast cells were isolated and purified by peritoneal lavage of rats (purity >98%) and co-cultured with mouse 3T3 fibroblasts to which they adhere. Cultures were incubated for 10 min at 37 degrees C with culture medium alone (Enriched Medium) or Enriched Medium containing either Nedocromil (10(-4) M) or Compound 48/80 (0.3 microg/ml) or Compound 48/80 and Nedocromil (0.3 microg/ml and 10(-4) M respectively). Supernatants were then assessed for histamine release, as a marker of mast cell activation and the cell monolayers were fixed and stained with an alcoholic-acidic toluidine blue solution and examined with a computerized image analyzer connected with a light microscope. Mast cells incubated in Enriched Medium or Nedocromil possessed similar morphometric parameters. Mast cells activated with Compound 48/80 (70% histamine release) had a significant increase in area and perimeter and a decrease in shape factor in comparison to mast cells in Enriched Medium alone. Simultaneous incubation of mast cells with Compound 48/80 and Nedocromil significantly inhibited their histamine release (36% histamine release) and the increase in area and perimeter, but did not affect significantly their shape factor, in comparison with mast cells incubated with Compound 48/80 alone. These data clearly show that there is a relationship between mast cell activation, consequent histamine release and changes in cell area, perimeter and shape factor and that Nedocromil not only inhibits mast cell histamine release but also the activation induced morphometric changes in mast cells.
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PMID:Activation and inhibition of mast cells degranulation affect their morphometric parameters. 1082 51

The effects of intravenous administration of nedocromil sodium were investigated in active and passive models of conjunctival immediate hypersensitivity in rats. In the active sensitization model, animals were immunized with ovalbumin 21 days prior to ocular instillation of a solution containing ovalbumin. Nedocromil sodium administered prior to antigen challenge significantly inhibited emergence of conjunctival edema and erythema (P < .05) and reduced mast cell degranulation (P < .02). In the passive-sensitization model, the conjunctiva in one eye was injected with ovalbumin antiserum 48 hours prior to intravenous administration of ovalbumin. Nedocromil sodium administered prior to antigen challenge significantly and dose-dependently reduced appearance of the signs of conjunctivitis (P < .01) as well as vascular leakage (P < .05). These data indicate that intravenous nedocromil sodium is effective in animal models of allergic conjunctivitis and may have potential for wider therapeutic application. These data are also consistent with results of clinical studies in which nedocromil sodium relieved symptoms of allergic conjunctivitis and further support a role for nedocromil sodium in the prevention of allergic conjunctivitis.
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PMID:Nedocromil sodium in two models of conjunctival immediate hypersensitivity. 1091 4


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