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)

This paper reports that the ionophore-induced slow-reacting substance (SRS) from mast cell tumor leukocytes is a member of a group of compounds called leukotrienes. Briefly, murine mastocytoma cells treated with calcium ionophore produced a SRS that caused guinea pig ileum to contract. This response could be reversed by an SRS antagonist, FPL 55712. Based on osotope incorporation experiments, spectrophotometry, and chemical degradation analyses, the SRS was identified. It is a cysteine-containing derivative of 5-hydroxy-7,9,11,14-icosatetraenoic acid, which was attached in a thioether linkage at C-6. The SRS was structurally related to previously identified epoxy and dihydroxy metabolites of arachidonic acid in leukocytes. The leukotrienes have the common feature of the presence of a conjugated triene. Leukotriene A is an intermediate in the formation of leukotriene B, and is proposed to be the precursor also of leukotriene C, the SRS chemically identified in this paper.
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PMID:Leukotriene C: a slow-reacting substance from murine mastocytoma cells. 4 Dec 40

When rat peritoneal mast cells were exposed to the ionophore A23187, a principle was released that possessed the biologic properties of slow reacting substance (SRS) from various sources. The response was dose, time, and temperature dependent with no activity being demonstrated in unstimulated cells. Supporting evidence that the mast cell product was similar or identical to SRS obtained from other sources include: 1) appropriate differential bioassay profile, 2) resistance to lipolysis and proteolysis, 3) acid lability and base stability, 4) inactivation by limpet arylsulfatase, and 5) inhibition by low concentrations FPL 55712. These data demonstrate that the isolated rat peritoneal mast cell contains the biosynthetic capacity to produce a bioreactive substance with the properties of SRS.
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PMID:Slow reacting substance (SRS) from ionophore A23187-stimulated peritoneal mast cells of the normal rat. I. Conditions of generation and initial characterization. 8 53

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

Stress- and ethanol-induced gastric mucosal damage are the two commonly used ulcer models in animals. They share some of the similarities but also have differences in the etiology of gastric ulceration. This article reviews the influences of various protective drugs on these two types of gastric damage in rats. Verapamil (a calcium antagonist) or N-ethylmaleimide (a sulfhydryl depletor) prevents cold restraint-, but potentiates ethanol-provoked gastric lesion formation. N-Acetylcysteine (a mucolytic agent) and acetaminophen (an antipyretic analgesic) have the opposite actions. Prostaglandins provide a much better antiulcer effect on ethanol-induced lesions. Cimetidine (a histamine H2-receptor antagonist) prevents only stress-induced mucosal damage. These differences in drug actions indicate that stress and ethanol may have dissimilar ulcerogenic mechanisms in rats. On the other hand, carbenoxolone (a mucus inducer), histamine H1-receptor antagonists, leukotriene inhibitors (FPL 55712 and nordihydroguaiaretic acid) and mast cell stabilizers (like zinc compounds, sodium cromoglycate, FPL 52694 and ketotifen), all protect against gastric mucosal damage by stress or ethanol in rats. However, the role of gastric sulfhydryls in both types of gastric lesions is still controversial. These findings imply that the two types of lesion formation share some of the ulcerogenic mechanisms. This communication attempts to analyze the various findings and to relate them to the etiology of stress and ethanol-induced gastric lesions. It also summarizes the uses, and the antiulcer mechanisms, of the drugs that have been studied utilizing these two animal ulcer models, and suggests their possible implications in man.
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PMID:The pharmacological differences and similarities between stress- and ethanol-induced gastric mucosal damage. 144 49

TMV F-IV, isolated from the venom of Trimeresurus mucrosquamatus (TMV), caused rat hind-paw edema in a dose-dependent manner. The maximum hind-paw swelling was reached at 1.5-2 h after subplantar injection of TMV F-IV. The edematous response caused by TMV F-IV was suppressed by the s.c. pretreatment with diphenhydramine, methysergide, acetylsalicylic acid or dexamethasone, and by the subplantar co-injection with FPL 55712, a SRS-A antagonist, and BN 52021 or L 652731, both PAF antagonists. Polymorphonuclear (PMN) leukocyte infiltration appeared within 1 h and gradually increased in the rat paw 3-6 h after edema induction. Compound 48/80 or methotrexate pretreatment also inhibited paw edema caused by TMV F-IV. In isolated mast cells, TMV F-IV increased the formation of PGE2 and LTB4 and caused a dose-dependent release of histamine and beta-glucuronidase. Since there are no significant differences in paw edema and mast cell degranulation responses between TMV F-IV and its DFP-modified analogue, the esterase activity may not be necessary in these models. These results indicate that mast cells. PMN leukocytes and some inflammatory mediators such as histamine, serotonin, arachidonate metabolites and PAF are involved in TMV F-IV induced paw edema.
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PMID:Rat hind-paw swelling effect of an edema-producing protein isolated from Trimeresurus mucrosquamatus snake venom. 171 14

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

The extent of acute gastric lesions produced by intragastric administration of ethanol in mice paralleled gastric leukotriene (LT) C4 levels. Furthermore, an inverse dose-response relationship was observed between the extent of gastric lesions and the number of mast cells in the gastric mucosa. When mice were pretreated with the 5-lipoxygenase inhibitor, AA-861, both the extent of ethanol-induced gastric lesions and the level of gastric LTC4 decreased dose-dependently. In contrast, when mice were pretreated with the LTC4 receptor antagonist, FPL-55712, the extent of ethanol-induced gastric lesions was depressed without significant reduction of gastric LTC4 level. These results indicate that both production of LTC4 and also subsequent binding of LTC4 to the receptors is important for the pathogenesis of gastric lesions and suggest that mast cell-derived LTC4 plays a major role in the development of ethanol-induced gastric lesions.
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PMID:The possible role of LTC4 in the pathogenesis of ethanol-induced gastric lesions in mice and their prevention by 5-lipoxygenase inhibitor AA-861, and leukotriene receptor antagonist FPL-55712. 190 Oct 44

Mast cells were shown to accumulate around the periphery of the invasive and metastatic rat mammary adenocarcinoma (MTLn3), and histological evidence of mast cell degranulation was observed during the later stages of this model. To assess the physiological role of mast cells in vivo we have used the mast cell-stabilising compound FPL 55618 applied i.p. daily at 1 mg kg-1 for 23 days. Using groups of 12 rats we have found that this compound inhibited tumour growth at the primary site by as much as 70% in most of the treated animals compared with the control group which received equivalent volumes of saline. When the drug treatment was stopped after 23 days, tumour growth of the test group accelerated over the next 7 days and reached a similar tumour size to that of control animals. Histological studies of the tumour and contiguous host tissue at day 24 of the experiment revealed numerous extra-tumoural mast cells often showing signs of degranulation at several sites around the tumour periphery in the control animals. Such observations were not seen in those animals receiving FPL 55618 where, in contrast to controls, numerous intact mast cells were often seen within the tumour mass. Following cessation of the MC-stabilising treatment progressive mast cell activation was evident within 2-4 days, primarily at the tumour periphery. In vitro studies have shown that drug concentrations equivalent to five times the in vivo dose had no effect on the proliferative rate or viability of the MTLn3 cells. Moreover, the proliferative rate of these cells in culture was significantly increased when exposed to soluble mast cell products. Thus our data indicate that a mast cell-stabilising compound has significant benefits in reducing tumour growth in vivo, an observation which supports the concept that mast cell:tumour cell interactions are important for the growth and invasive properties demonstrated by this model of breast carcinoma.
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PMID:Mast cell modulation of tumour cell proliferation in rat mammary adenocarcinoma 13762NF. 206 44

We studied the in vitro effects of FPL-52694 [5-(2-hydroxypropoxyl)-8-propyl-4-oxo-4H-benzopyran-2-carboxylic acid Na] on histamine release from rat peritoneal mast cells. These cells exposed to ascaris antigen, compound 48/80 or the ionophore A 23187 concentration-dependently released histamine. About a 30-40% histamine release was obtained by 1 X 10(-4) g/ml of antigen, 1 X 10(-7) g/ml of compound 48/80 and A 23187. FPL-52694 (10(-9)-10(-4) g/ml) concentration-dependently inhibited the histamine release from mast cells in response to antigen (1 X 10(-4) g/ml) and compound 48/80 (1 X 10(-7) g/ml), but only slightly inhibited the histamine release induced by A 23187 (1 X 10(-7) g/ml). Similar results were obtained with disodium cromoglycate (DSCG), in the same dose ranges. However, the inhibitory activity of FPL-52694 on histamine release by antigen and compound 48/80 was approximately 10 times more potent than that of DSCG at certain concentrations. Tachyphylaxis was observed when these two agents were preincubated with mast cells for 10 min. These results show FPL-52694 to be a novel mast cell stabilizer.
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PMID:Characterization of FPL-52694 [5-(2-hydroxypropoxyl)-8-propyl-4-oxo-4H-benzopyran-2-carboxylic acid Na] on histamine release from rat peritoneal mast cells induced by antigen, compound 48/80 and A 23187. 241 56

With the use of a collagenase dispersion technique, cells were isolated from the lamina propria of the human small and large intestine. The cell suspensions contained 8% mast cells, which on average contained 1 to 2 pg of histamine/cell. With the use of histochemical procedures based upon fixative sensitivity and dye binding, which identify functionally distinct mast cell subtypes in the rat, dispersed human intestinal mast cells contained approximately equal proportions of two histochemical subtypes analogous to those in the rat. Whether these are functionally distinct as in the rat remains to be determined. The histochemically mixed mast cell populations from the human intestinal mucosa secreted histamine in a dose- and energy-dependent manner in response to anti-IgE and A23187, but not 48/80. Theophylline, doxantrazole, quercetin, and salbutamol all significantly inhibited anti-IgE-induced histamine secretion by human intestinal mast cells, but cromolyn sodium and the experimental antisecretory drugs, nedocromil sodium and FPL 52694, did not inhibit histamine secretion by the mast cell mixture to a statistically significant extent. Cromolyn sodium inhibited histamine secretion by 15 to 30%, and whether this reflected inhibition of one of the two histochemical mast cell subtypes to a greater extent than the other or all the cells to a minimal degree remains to be established. Control investigations of the intestinal cell isolation procedure indicated that these qualities did not reflect effects of the cell dispersal procedure. Further characterization and analysis of intestinal mast cells is essential to determine if functionally distinct mast cell subtypes exist in human tissues.
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PMID:Mast cells from the human intestinal lamina propria. Isolation, histochemical subtypes, and functional characterization. 243 1


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