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)

Protamine stimulates guinea-mesenteric mast cells in a concentration-dependent manner, both histamine release and mast cell degranulation being correlated. Mast cell stimulation is blocked by 2,4-DNP (0.03 mM), low (0 degrees C) and high (45 degrees C) temperature. The inhibitory effect by 2,4-DNP is reversed by glucose (5.0 mM), while incubation at 37 degrees reverses that by low and high temperature. Lack of calcium from the incubation medium does not influence mast cell stimulation by protamine. However calcium chelation with EDTA (2.0 mM) or EGTA (2.0 mM) blocks mast cell stimulation. Addition of calcium (0.9 mM) reverses this inhibition. These observations indicate that guinea-pig mast cell stimulation by protamine is a nonlytic, energy and calcium dependent process, similar to anaphylaxis, but different from that of other basic compounds which induce mast cell lysis.
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PMID:Non cytotoxic guinea-pig mesenteric mast cell stimulation by protamine. 245 98

Rat peritoneal fluid mast cell present parallel increases in cell area (swelling), and in hydrolytic activity on the trypsin substrate p-tosyl arginine methyl ester (TAME), when placed in Tris buffers of concentrations between 0.15 and 0.03 M. Under these conditions, cells do not degranulate and preserve their trypsin-like enzyme activity after low speed centrifugation. Exposure to more dilute Tris buffers, between 0.015 and 0.003 M, leads to cell rupture accompanied by progressive degranulation and loss of activity on TAME. Protamine, a heparin antagonist prevented this loss when added to mast cells prior to hyposmotic lysis, or lysis by sonication or repeated periods of freezing and thawing. Enzyme activity released in the presence of protamine was fully recovered in supernates of cell lysates submitted to low speed centrifugation. Controlled swelling of mast cells propitiates the expression of trypsin-like activity, possibly by facilitating enzyme-substrate interaction. Cell lysis on the contrary, leads to inactivation of such activity, possibly by enzyme binding to heparin in exposed mast cell granules.
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PMID:Hyposmotic swelling leads to the expression of trypsin-like activity by rat peritoneal fluid mast cells. 330 42

Protamine sulfate, known for a long time as a histamine releaser, was labeled with a fluorescent dye (FITC). This conjugate was shown to stain selectively the mast cell fraction of rat peritoneal cells. Within a few seconds, the protamine was found inside the cells. Although the cells had lost their histamine completely, no granules were found outside the cells. In the electron microscope, the protamine treated mast cells showed a loss of the electron density of their granules, a vacuolization, and other signs of histamine release. Evidence for a direct connection between the vacuoles and the extracellular fluid was gained by incubating mast cells in FITC-labeled human serum albumin followed by the addition of unlabeled protamine. After washing, the fluorescence was found to be located inside the cells, demonstrating an influx of the FITC-HSA under the influence of protamine. The protamine-induced release reaction is increased after addition of Ca2+, reduced by lowering the temperature, addition of 2-deoxyglucose, or cytochalasin B. Disodium cromoglycate also diminished the histamine release in a dose dependent manner. Protamine did not induce a loss of lactate dehydrogenase from the mast cells. The release reaction is mediated by the cell membrane, as shown by the releasing activity of insolubilized protamine. We conclude that the protamine-induced release is a non-cytotoxic reaction, fulfilling some criteria of the anaphylactic histamine release.
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PMID:[Mode of action of protamine sulfate on histamine secretion in the rat mast cells]. 616 92

Protamines are polycationic proteins that are widely used for neutralisation of the anticoagulant action of heparin. However, several reports have shown adverse, mast cell-dependent reactions to protamine. The exact mechanism by which protamine causes these adverse effects is not clear. In the present study, the possibility that protamine may influence mast cell chymase function was investigated. Mast cell chymase is in vivo recovered in a macromolecular complex with heparin proteoglycan, and this interaction is essential for expression of optimal enzymatic activity. Protamine was shown to strongly reduce the activity of mast cell chymase by a mechanism that involved displacement of the chymase from heparin proteoglycan.
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PMID:Mast cell chymase in complex with heparin proteoglycan is regulated by protamine. 892 90

Tryptase may be a key mediator in mast cell-mediated inflammatory reactions. When mast cells are activated, they release large amounts of these tetrameric trypsin-like serine proteases. Tryptase is present in a macromolecular complex with heparin proteoglycan where the interaction with heparin is known to be essential for maintaining enzymatic activity. Recent investigations have shown that tryptase has potent proinflammatory activity, and inhibitors of tryptase have been shown to modulate allergic reactions in vivo. Many of the tryptase inhibitors investigated previously are directed against the active site. In the present study we have investigated an alternative approach for tryptase regulation. We show that the heparin antagonists Polybrene and protamine are potent inhibitors of both human lung tryptase and of recombinant mouse tryptase (mouse mast cell protease 6). Protamine inhibited tryptase in a competitive manner whereas Polybrene showed noncompetitive inhibition kinetics. Treatment of tetrameric, active tryptase with Polybrene caused dissociation into monomers, accompanied by complete loss of enzymatic activity. The present report thus suggests that heparin antagonists potentially may be used in treatment of mast cell-mediated diseases such as asthma.
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PMID:Heparin antagonists are potent inhibitors of mast cell tryptase. 1140 83

This study sought to investigate the effects of nadroparine on an in vivo experimental model of type I hypersensitivity response in the rat conjunctiva. Following drug application onto the eye, either before or after challenge with the mast cell degranulator, basic polyamine compound 48/80, the conjunctival histamine content and the nitrite levels in the conjunctival lavage fluid were quantified fluorometrically and spectrophotometrically, respectively. Instillation into the eye of nadroparine inhibited the C48/80-induced decreases in conjunctival histamine and the delayed increases in nitrite levels, without influencing basal mediator levels. Protamine did not induce histamine release and only partially reversed the effects of nadroparine post-challenge, yet it had no effect on the protective action of the drug when administered prior to degranulation. The results showed that nadroparine was equally effective in attenuating the effects of compound 48/80 in the eye when administered topically either before or after challenge.
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PMID:Nadroparine inhibits the hypersensitivity response in the conjunctiva. 1463 83

The incidence of anaphylaxis during anesthesia has been reported to range from 1 in 4000 to 1 in 25,000. Anaphylaxis during anesthesia can present as cardiovascular collapse, airway obstruction, and/or skin manifestation. It can be difficult to differentiate between immune and nonimmune mast cell-mediated reactions and pharmacologic effects from the variety of medications administered during general anesthesia. In addition, cutaneous manifestations of anaphylaxis are less likely to be apparent when anaphylaxis occurs in this setting. The evaluation of IgE-mediated reactions to medications used during anesthesia can include skin testing to a variety of anesthetic agents. Specifically, thiopental allergy has been documented by skin tests. Neuromuscular blocking agents such as succinylcholine can cause nonimmunologic histamine release, but there have also been reports of IgE-mediated reactions in some patients. Reactions to opioid analgesics are usually caused by direct mast cell mediator release rather than IgE-dependent mechanisms. Antibiotics that are administered perioperatively can cause immunologic or nonimmunologic reactions. Protamine can cause severe systemic reactions through IgE-mediated or nonimmunologic mechanisms. Blood transfusions can elicit a variety of systemic reactions, some of which might be IgE-mediated or mediated through other immunologic mechanisms. The management of anaphylactic reactions that occur during general anesthesia is similar to the management of anaphylaxis in other situations.
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PMID:Anaphylaxis during the perioperative period. 2588 4