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)

The generation of slow reacting substance (SRS) from ionophore A23187-stimulated rat peritoneal mast cells was enhanced by arachidonic acid (AA). This SRS generation was inhibited by 5,8,11,14-eicosatetraynoic acid (ETYA), an acetylenic analogue of AA and an inhibitor of both fatty acid cyclooxygenase and lipoxygenase. Indomethacin, a fatty acid cyclooxgenase inhibitor, had an enhancing effect upon SRS generation. This suggests SRS generation occurred through an ETYA sensitive step--perhaps a lipoxygenase. Radiolabel from [14C]-AA was incorporated into SRS with comigration of radioactivity and bioreactivity in silicic acid and thin layer chromatographies. Upon silicic acid chromatography, the active principle was eluted in the methanol fraction. Two-dimensional thin layer chromatography revealed chromatographic separation from other known spasmogenic substances and phospholipids. Mast cell SRS was found to display physiochemical properties similar to those of rat basophilic leukemia cell SRS, namely: that mast cell SRS generation was 1) enhanced by arachidonic acid; 2) inhibited by ETYA but not by indomethacin; 3) incorporation of [14C]-AA into the active principle; and 4) similar behavior during purification in silicic acid and thin layer chromatographies.
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PMID:Slow reacting substance (SRS) from ionophore A23187-stimulated peritoneal mast cells of the normal rat. II. Evidence for a precursor role of arachidonic acid and further purification. 37 31

1. Intravenous administration of substance P (SP) or of the NK1 selective agonist [beta-Ala4, Sar9, Met (O2)11] SP-(4-11) increased vascular permeability in the urinary bladder of urethane-anaesthetized rats, providing evidence for an NK1 receptor-mediated inflammatory response. 2. BW 755C, a dual inhibitor of arachidonate cyclo-oxygenase and lipoxygenase, significantly reduced the plasma extravasation induced by SP, but did not modify the effect of [beta-Ala4, Sar9, Met (O2)11] SP-(4-11). 3. SP-induced microvascular leakage was also inhibited by systemic pretreatment with indomethacin or with the prostaglandin receptor antagonist SC-19220, while it was unaffected by the selective 5-lipoxygenase inhibitor BW A4C or the leukotriene antagonist FPL 55712. 4. Pretreatment of rats with the mast cell degranulating agent compound 48/80 significantly attenuated the inflammatory effect of SP. Indomethacin administration to 48/80-pretreated animals failed to produce further inhibition. 5. These findings indicate that intravascular SP promotes plasma exudation in rat urinary bladder through an NK1-mediated effect on venular permeability and the release of cyclo-oxygenase metabolites of arachidonic acid. The latter effect largely derives from the interaction of the neuropeptide with mast cells.
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PMID:Microvascular leakage induced by substance P in rat urinary bladder: involvement of cyclo-oxygenase metabolites of arachidonic acid. 138 Sep 64

The response to antigen (trinitro-phenyl-haptenized ovalbumin) and the modulatory role of several antiallergic drugs was studied in isolated hearts from actively sensitized rats. Antigen induced a triphasic effect on coronary flow (CF) and left ventricular pressure (LVP) characterized by short-term increase (0-1.5 min = phase 1) and a severe decrease (1.5-7.5 min = phase 2) followed by a less pronounced long-lasting decrease (7.5- greater than 20 min = phase 3). The first phase was accompanied with a substantial release of 5-hydroxytryptamine (5-HT), histamine, and leukotrienes measured in cardiac effluents. The histamine2 (H2)-receptor antagonist cimetidine (60 microM) reversed the antigen-induced increase in CF to a decrease. In contrast, H1-receptor blockade by mepyramine (6 microM) had no effect. Methysergide (10 microM) and ketotifen (0.1 microM) evoked a mild suppression during all three phases. Indomethacin (10 microM) was almost inactive while tolfenamic acid (1 microM) was slightly active in this respect during phase 2. Addition of the 5-lipoxygenase inhibitor AA 861 (1 microM) resulted in complete suppression of the antigen-induced decrease in CF. The leukotriene antagonist FPL 55712 (5 and 50 nM) evoked a dose-dependent suppression with respect to the anaphylactic phases 2 and 3. A similar reduction was obtained with sodium cromoglycate (1 mM). AA 861, FPL 55712, and sodium cromoglycate also suppressed the antigen-induced decrease in LVP. The antigen-induced histamine release was not affected by the aforementioned drugs. Our results provide evidence that H2-receptor blockade during cardiac anaphylaxis enhances coronary constriction and may be detrimental in this condition. On the other hand, leukotriene antagonists and 5-lipoxygenase inhibitors may exert beneficial effects during cardiac anaphylaxis. Further experiments in this area are needed to clarify the precise role of mast cell-generated mediators in cardiac anaphylaxis possibly leading to new therapeutic approaches in this life-threatening disorder.
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PMID:Characterization and modulation of antigen-induced effects in isolated rat heart. 172 33

1. Zymosan, an activator of the alternative complement pathway, (2 to 16 mg kg-1) injected intravenously via the tail vein of anaesthetized rats, dose-dependently increased the vascular permeability of lung parenchyma, as measured by the accumulation of 125I-labelled albumin in lungs. 2. Pretreatment of the animals with cyclo-oxygenase inhibitors, indomethacin or ketoprofen (3 mg kg-1) or with the lipoxygenase and cyclo-oxygenase inhibitor, BW755C (40 mg kg-1) abolished the vascular permeability changes induced by zymosan (16 mg kg-1). Neither, the PAF antagonist, WEB 2086 (10 mg kg-1) nor the antagonist of mast cell amines, mepyramine and methysergide (3 mg kg-1) affected the plasma exudation in lungs. Zymosan did not induce any accumulation of labelled albumin in lungs of rats made leukopenic by rabbit anti-neutrophil serum. 3. Zymosan (16 mg kg-1) increased the haematocrit. This increase was not modified by indomethacin but reduced by WEB 2086. 3. Intravenous injection of zymosan (3 and 8 mg kg-1) in anaesthetized rats transiently increased right ventricular blood pressure and pulmonary arterial pressure, accelerated respiratory rate and decreased systemic blood pressure. 5. WEB 2086 largely reduced the systemic hypotension but did not affect the increase of pulmonary vascular resistance. Indomethacin inhibited the increase of blood pressure in the right ventricle and the modification of the respiratory rate. This drug did not inhibit but increased the systemic hypotension induced by zymosan. 6. Zymosan (16 mg kg-1) reduced serum complement haemolytic activity by 46%. 7. These data suggest that the pulmonary vascular changes induced by intravascular complement activation with zymosan in rats are mediated by neutrophils and prostanoids while the systemic vascular effects depend mainly on PAF.
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PMID:Dissociation between the effects of zymosan on the systemic and pulmonary vessels of the rat. 179 19

WEB 2086 reduced the increase in vascular permeability induced by platelet-activating factor (PAF-acether) in rat abdominal skin. Injected alone, WEB 2086 did not modify the oedema induced by zymosan in rat paw. However, administered with methysergide and mepyramine, WEB 2086 reduced the development of this oedema during the first two hours. WEB 2086 also reduced the volume of the exudate induced by zymosan in the peritoneal cavity and its content in leucocytes. Methysergide and mepyramine reduced the volume of the peritoneal exudate. BW755C inhibited the peritoneal accumulation of fluid and of leucocytes. Indomethacin was inactive. The inhibitory effect of WEB 2086 suggests that PAF-acether is involved in the inflammatory responses induced by zymosan in rats beside other endogenous factors such as lipoxygenase products and mast cell amines.
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PMID:Inhibition by WEB 2086, a PAG-acether antagonist of oedema and peritonitis induced by zymosan in rats. 207 45

The allergic bronchoconstriction in guinea pigs has been attributed mainly to the release of mast cell mediators. Histamine has been involved in the first minutes of the anaphylactic reaction and new-formed compounds in the subsequent response. In this asthma model the vagal influence has been sparsely investigated. In the present work we evaluated the pharmacological modification of the acute allergic bronchoconstrictor response in guinea pigs sensitized to ovalbumin through aerosol exposure. Pyrilamine (20 micrograms/kg), diethylcarbamazine (a lipoxygenase inhibitor, 10 mg/kg) and dexamethasone (4 mg/kg) each reduced the antigen-induced bronchoconstriction throughout the 30 min studied. Indomethacin (3.1 mg/kg) did not modify the response to the antigen. Atropine (2 mg/kg) plus bilateral vagotomy also diminished this response from 5 min onward. On the other hand, from 5 min ahead pyrilamine-resistant bronchoconstriction was partially inhibited by dexamethasone, and it was almost completely blocked during all of the response when atropine plus bilateral vagotomy were added to dexamethasone. Dipyridamole (an inhibitor of the adenosine uptake, 0.4 mg/kg) enhanced the bronchoconstriction, though this was significant only in the 2-5 min time-interval of the response. These results suggest that histamine and vagal influence play an important role in the whole response to antigen, that other mediators, probably leukotrienes, participate in this response from 5 min onward, and that adenosine could exert a potentiation effect on this response.
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PMID:Pharmacological characterization of mediators and vagal influence in the acute allergic bronchoconstriction in guinea pigs. 228 Jul 95

The release of prostaglandin D2 (PGD2), prostaglandin E2 (PGE2), and histamine induced by antigen and compound 48/80 was studied using an in vitro model of anaphylaxis in guinea pig skin. Abdominal skin from ovalbumin-sensitized guinea pigs was cut into 0.5-1.0 mm-thick slices which were incubated in Tyrode solution at 37 degrees C with or without either ovalbumin or 48/80. Released PGD2 and PGE2 were measured by radioimmunoassay and gas chromatography-mass spectrometry, respectively. Release of PGD2 was detectable at 2 min after challenge (50 micrograms/ml ovalbumin), reaching a maximum at about 15 min. Histamine release was more rapid, achieving 50% of maximum at about 4 min compared to about 7 min for PGD2. In 11 experiments incubation with ovalbumin (50 micrograms/ml for 10 min) induced a significant 6-fold increase in PGD2 compared to unchallenged controls (399 +/- 53 and 67 +/- 19 ng/g dry weight skin, respectively; mean +/- SEM) and a net 47.2% histamine release. In contrast, a smaller (27%) rise in PGE2 was found. Indomethacin (14 microns) completely suppressed evoked PGD2 and PGE2 synthesis without evident effect on histamine release, suggesting that the release of histamine in this model is not dependent on prostaglandin production. The mast cell degranulating agent compound 48/80 (50 micrograms/ml) released significant amounts of PGD2 (340 +/- 86 ng/g skin compared to 89 +/- 30 ng/g for control skin, n = 5) but had no appreciable effect on PGE2. These results show that guinea pig skin can synthesize significant quantities of PGD2 in anaphylactic reactions. Prostaglandin D2 produced in acute allergic reactions in skin in vivo may contribute to the inflammatory reaction, either directly or in synergism with other mediators.
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PMID:Prostaglandin D2 release by guinea pig skin during in vitro anaphylaxis induced by antigen and compound 48/80. 243 54

The effect of antigen (ovalbumin) challenge on smooth muscle contraction and release of sulfidopeptide leukotrienes and histamine from superfused, actively sensitized guinea pig trachea was examined. Maximum concentrations of ovalbumin caused the release of 16 +/- 4 ng/g immunoreactive sulfidopeptide leukotriene (i-LT) and 27 +/- 3% of the endogenous histamine (x +/- S.E.M., n = 19). High performance liquid chromatography combined with a sulfidopeptide leukotriene radioimmunoassay was used to demonstrate that on a molar basis, approximately 10% of the leukotriene immunoreactivity recovered was LTC4, 45% LTD4 and 45% LTE4. Indomethacin slightly increased ovalbumin-induced histamine release and substantially enhanced (3-fold) i-LT release from the trachea. Neither the profile nor rate of sulfidopeptide leukotriene release was altered by indomethacin. Indomethacin had no effect on the maximum amplitude of the antigen-induced contraction but significantly enhanced the magnitude of contraction observed after 10 min of antigen exposure. These results demonstrate that actively sensitized airways synthesize and release sulfidopeptide leukotrienes upon challenge with specific antigen and that endogenously formed LTC4 is efficiently metabolized to LTD4 and LTE4. The results with indomethacin support the hypothesis that indomethacin potentiates antigen-induced airway contraction in vitro by enhancing the release of mast cell associated mediators.
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PMID:Antigen-induced sulfidopeptide leukotriene release from the guinea pig superfused trachea. 244 85

Antigen challenge of jejunal epithelium from rats sensitized to egg albumin induces an active Cl- secretory process secondary to release of mucosal mast cell mediators. The present study was designed to define the relative role of these mast cell mediators and the enteric nervous system in the transport abnormalities associated with intestinal anaphylaxis. Net ion transport of stripped jejunal tissue from sensitized and sham-treated animals was studied in Ussing chambers. The Cl- secretory response induced by egg albumin during intestinal anaphylaxis was similar to that after addition of 5-hydroxytryptamine (5-HT), histamine, and prostaglandins D2 and E2 to jejunal tissue. Cinanserin, a 5-HT2-receptor antagonist, virtually abolished the response to 5-HT and totally abolished the response to egg albumin. Methysergide, a 5-HT1-receptor antagonist had no effect on either response. Indomethacin, an inhibitor of prostaglandin synthesis, significantly inhibited the 5-HT and egg albumin response. Diphenhydramine, an H1-receptor antagonist and cimetidine, an H2-receptor antagonist both significantly inhibited the histamine response but neither altered the response to egg albumin. Atropine, an anticholinergic, and tetrodotoxin, a nerve blocker, did not inhibit the antigen induced anaphylactic response. These results indicate that 5-HT, acting through 5-HT2 receptors is largely responsible for the transport abnormalities seen in intestinal anaphylaxis induced by egg albumin while prostaglandins appear to play a partial role. The findings do not support a role for the enteric nervous system for the egg albumin induced changes in Cl- secretion.
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PMID:Intestinal anaphylaxis in the rat: mediators responsible for the ion transport abnormalities. 251 72

Plasma extravasation responses to silver nitrate (AgNO3), histamine, 5-hydroxytryptamine (5-HT), bradykinin and prostaglandin E1 (PGE1) in the abdominal skin, hindpaw ankle joint and subplantar region of rats have been investigated using the Evans blue dye leakage technique. All substances tested produced plasma extravasation and combination of low doses (5 x 10(-10) mol) of either histamine or bradykinin with PGE1 (5 x 10(-10) mol) exhibited potentiation of responses of all regions. Responses to AgNO3 (1 x 10(-6) mol) were significantly reduced by the H1 receptor antagonist, mepyramine, only in the abdominal skin, but the H2 receptor antagonist metiamide reduced the responses at subplantar and ankle joint regions. Indomethacin significantly reduced the AgNO3 responses at the ankle joint only, but aprotinin reduced it at the other two regions. In rats pretreated with a combination of all antagonists the residual plasma extravasation response to AgNO3 was very small, indicating that the response could be almost totally accounted for by the combined actions of mast cell amines, kinins and prostanoids. The finding that prostanoids played a major role in the plasma extravasation response of the rat ankle joint to AgNO3 indicated that this model would be useful for the screening of non-steroidal anti-inflammatory drugs.
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PMID:Mediators of the plasma extravasation response to silver nitrate in the rat skin, subplantar region and ankle joint. 256 64


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