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)

1. The effect of purified crotapotin, a non-toxic non-enzymatic chaperon protein normally complexed to a phospholipase A2 (PLA2) in South America rattlesnake venom, was studied in the acute inflammatory response induced by carrageenin (1 mg/paw), compound 48/80 (3 micrograms/paw) and 5-hydroxytryptamine (5-HT) (3 micrograms/paw) in the rat hind-paw. The effects of crotapotin on platelet aggregation, mast cell degranulation and eicosanoid release from guinea-pig isolated lung were also investigated. 2. Subplantar co-injection of crotapotin (1 and 10 micrograms/paw) with carrageenin or injection of crotapotin (10 micrograms/paw) into the contralateral paw significantly inhibited the carrageenin-induced oedema. This inhibition was also observed when crotapotin (10-30 micrograms/paw) was administered either intraperitoneally or orally. Subplantar injection of heated crotapotin (15 min at 60 degrees C) failed to inhibit carrageenin-induced oedema. Subplantar injection of crotapotin (10 micrograms/paw) also significantly inhibited the rat paw oedema induced by compound 48/80, but it did not affect 5-HT-induced oedema. 3. In adrenalectomized animals, subplantar injection of crotapotin markedly inhibited the oedema induced by carrageenin. The inhibitory effect of crotapotin was also observed in rats depleted of histamine and 5-HT stores. 4. Crotapotin (30 micrograms/paw) had no effect on either the histamine release induced by compound 48/80 in vitro or on the platelet aggregation induced by both arachidonic acid (1 nM) and platelet activating factor (1 microM) in human platelet-rich plasma. The platelet aggregation and thromboxane B2 (TXB2) release induced by thrombin (100 mu ml-1) in washed human platelets were also not affected by crotapotin. In addition, crotapotin (10 microg/paw) did not affect the release of 6-oxo-prostaglandin Fla, and TXB2 induced by ovalbumin in sensitized guinea-pig isolated lungs.5. Our results indicate that the anti-inflammatory activity of crotapotin is not due to endogenous corticosteroid release or inhibition of cyclo-oxygenase activity. It is possible that crotapotin may interact with extracellular PLA2 generated during the inflammatory process thereby reducing its hydrolytic activity.
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PMID:Inhibition of carrageenin-induced rat paw oedema by crotapotin, a polypeptide complexed with phospholipase A2. 753 90

1. We have investigated the mechanism of bradykinin (BK)-induced plasma extravasation into the knee joint of the anaesthetized rat. Accumulation of [125I]-human serum albumin within the synovial cavity was used as a marker of increased vascular permeability. 2. Perfusion with BK (1 microM) produced significant plasma extravasation into the knee which was inhibited by co-perfusion of the selective bradykinin B2 receptor antagonist D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]-bradykinin (Hoe 140, 200 nM). 3. The bradykinin B1 receptor agonist, [des-Arg9]-BK (up to 100 mM), did not induce plasma extravasation into the knee joint, over this time period. 4. Chemical sympathectomy by chronically administered 6-hydroxydopamine (6-OHDA) did not inhibit bradykinin-induced plasma extravasation. Acute intra-articular perfusion with 6-OHDA (to stimulate transmitter release from sympathetic nerve terminals) at concentrations up to 50 mM did not induce significant plasma extravasation. Intra-articular perfusion of 100 mM 6-OHDA induced significant plasma extravasation but produced severe systemic toxicity. 5. The selective neurokinin1 (NK1) receptor antagonist, RP67580 (230 nmol kg-1), or receptor antagonists for the mast cell products histamine and 5-hydroxytryptamine did not significantly inhibit BK-induced plasma extravasation. 6. Co-perfusion of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) (1 mM) did not significantly inhibit the response to BK. 133Xe clearance from L-NAME (1 mM)-injected joints was significantly (P < 0.05) reduced compared to D-NAME injected joints, suggesting a reduction in blood flow as a result of decreased basal NO production. Systemic administration of L-NAME at doses sufficient to produce significant and sustained elevation of blood pressure (5 or 30 mg kg-1, i.v. 15 min prior to BK perfusion) also failed to significantly inhibit the BK-induced response.7 We conclude that, in normal joints, BK induces plasma extravasation by acting on bradykinin B2 receptors and that this response is not dependent on secondary release of mediators from sympathetic nerve terminals, sensory nerves, mast cells or on generation of NO.
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PMID:Mechanism of bradykinin-induced plasma extravasation in the rat knee joint. 758 84

Colonic smooth muscle function may be altered in food protein hypersensitivity reactions and could contribute to the clinical manifestation of diarrhea. To characterize such functional changes and elucidate the mediators and mechanisms involved. Hooded-Lister rats were sensitized by intraperitoneal injection of egg albumin (10 micrograms), and controls were sham sensitized with saline. Fourteen days later the contractility of longitudinally oriented distal colonic segments (mucosa intact) were studied in standard tissue baths in response to antigen (Ag) or other agents. After Ag exposure, a contractile response was documented in animals that were sensitized [specific immunoglobulin E (IgE) antibody levels > or = 1:64] and was specific for the sensitizing Ag. Mast cell involvement was suggested by a significant reduction in the number of granulated mucosal mast cells in sensitized tissues after Ag challenge and in the magnitude of the Ag-induced contractile response in the presence of mast cell stabilizers. The antigen-induced response was significantly and independently inhibited by both cyclooxygenase and lipoxygenase enzyme inhibitors and by leukotriene D4 and platelet activating factor receptor antagonists. The Ag-induced response was resistant to histamine and the 5-hydroxytryptamine antagonists, atropine and tetrodotoxin. These results suggest that the food protein-induced contraction of colonic longitudinal smooth muscle in the sensitized rat is due to IgE-mediated mast cell activation with the subsequent production and release of membrane-derived mediators that, in vitro, act directly on the smooth muscle.
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PMID:Intestinal anaphylaxis: mediation of the response of colonic longitudinal muscle in rat. 776 60

1. The synthetic cationic polypeptide, poly-L-arginine (0.03-1 mg ml-1) induced concentration-dependent contraction of guinea-pig and rat isolated trachea. In guinea-pig isolated trachea, this response was attenuated in the presence of the muscarinic cholinoceptor antagonist, atropine (0.1 microM) and augmented by the acetylcholinesterase inhibitor, ecothiophate (0.1 microM). The neuronal sodium channel blocker, tetrodotoxin (3 microM) failed to alter the contractile response to poly-L-arginine and acetylcholine. 2. The contractile response to poly-L-arginine in rat isolated trachea was inhibited in the presence of atropine (0.1 microM) and the 5-hydroxytryptamine (5-HT) receptor antagonist, methysergide (1 microM). Treatment of rat tracheal preparations with capsaicin (100 microM) or tetrodotoxin (3 microM) failed to alter the contractile response to poly-L-arginine. In contrast, ecothiophate (0.1 microM) augmented the contractile response to poly-L-arginine in rat isolated trachea. 3. Electrical field stimulation (5 Hz, 2 min) of epithelium-denuded guinea-pig tracheal preparations preloaded with [3H]-choline resulted in a contractile response and the simultaneous efflux of radioactivity into the superfusate. Both these responses were abolished in the presence of tetrodotoxin (1.5 microM). Poly-L-arginine (1 mg ml-1) also increased the efflux of total radioactivity from epithelium-denuded guinea-pig isolated tracheal preparations preloaded with [3H]-choline, but this response was tetrodotoxin-insensitive. The negatively charged polyanion, heparin (1 mg ml-1) failed to increase significantly the efflux of radioactivity from epithelium-denuded preparations. 4.In conclusion, the synthetic cationic polypeptide, poly-L-arginine, caused contraction of guinea-pig isolated tracheal preparations via the release of acetylcholine from parasympathetic nerves. Similarly,poly-L-arginine-induced contraction of rat isolated trachea is secondary to the release of acetylcholine from parasympathetic nerves and/or the release of mast cell-derived 5-HT.
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PMID:Poly-L-arginine-mediated release of acetylcholine from parasympathetic nerves in rat and guinea-pig airways. 792 18

The effects of pulmonary denervation and rejection on contractions of bronchial smooth muscle and epithelial modulation of these contractions were studied in dogs after denervation in right lung autotransplantation (n = 6) and acute rejection after right lung allotransplantation (n = 8). Immunosuppression was withdrawn from the latter group after 5 days; rejection developed after 3 additional days. A significant (p < 0.05) increase in mean peak airway pressure occurred with rejection of allotransplanted lungs. Rings cut from third-order bronchi of transplanted and contralateral unoperated (native) lungs in each animal were suspended in organ chambers for the measurement of isometric force. In some rings, the epithelium was removed mechanically. Acetylcholine (cholinergic neurotransmitter), serotonin (platelet-product), histamine (mast cell product), and endothelin-1 (endothelium-derived contracting factor) caused concentration-dependent contractions in all rings. In bronchi from native lungs, rings with epithelium contracted less than those without epithelium. This difference was lost after autotransplantation. The smooth muscle and epithelium were affected differently by autotransplantation. Contractions of rings without epithelium decreased in response to acetylcholine and endothelin-1, whereas contractions of rings with epithelium increased in response to histamine and 5-hydroxytryptamine (p < 0.05). During acute rejection, contractions were the same as those after autotransplantation. Bronchial content of endothelin increased fourfold with rejection. Relaxations to isoproterenol and prostaglandin E2 were similar in both groups. In conclusion, denervation reduced the ability of the smooth muscle to contract. The degree of acute pulmonary rejection seen in this study did not further affect bronchial contractions. Modulation of contractions by the bronchial epithelium was lost with both denervation and rejection.
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PMID:Bronchial contractions in transplanted lungs. Influence of denervation, acute rejection, and the bronchial epithelium. 823 Dec

Altered intestinal motility and diarrhea are features of food protein-induced intestinal anaphylaxis in the conscious rat. These experiments were performed to determine the mediator(s) responsible for jejunal circular smooth muscle contraction during this response. Hooded-Lister rats were sensitized by intraperitoneal injection of 10-micrograms egg albumin, and controls were sham-sensitized with saline. Fourteen days later the contractility of the circular muscle in jejunal segments (mucosa intact) was examined in standard tissue baths in response to antigen (Ag) or other agents. While control and sensitized tissues contracted in similar fashion in response to stretch, bethanechol, histamine, or 5-hydroxytryptamine (5HT), Ag contracted only the segments of sensitized animals. The contractile response was: (1) specific to the sensitizing Ag, as bovine serum albumin did not induce contraction and (2) could be passively transferred with serum containing specific immunoglobulin E antibody (IgE-Ab). Concanavalin A, which degranulates both mucosal and connective tissue-type mast cells, and compound 48/80, which degranulates only connective tissue-type mast cells produced contractile responses. Ag-induced contraction was significantly inhibited by the mucosal and connective tissue-type mast cell stabilizer doxantrazole, but not the connective tissue mast cell stabilizer disodium cromoglycate. Diphenhydramine and cimetidine together significantly inhibited histamine-induced contraction, but failed to effect the Ag-induced contraction in sensitized tissues. While the contractile response to 5HT was reduced in the presence of methysergide (5HT1-receptor antagonist), cinanserin (5HT2-receptor antagonist), and ICS 205-930 (5HT3-receptor antagonist), only cinanserin significantly inhibited the contractile response to Ag. Indomethacin significantly inhibited Ag-induced contraction. Ag-induced contraction was resistant to atropine and tetrodotoxin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mediation of anaphylaxis-induced jejunal circular smooth muscle contraction in rats. 844 68

Mast cell-deficient mutant mice and their normal littermates were used to determine whether activation of mast cells by anti-IgE enhances airway responsiveness to bronchoactive agonists in vivo. Pulmonary conductance was used as an index of airway response as the mice were challenged with increasing intravenous doses of methacholine (Mch) or 5-hydroxytryptamine (5-HT). Mast cell activation with anti-IgE enhanced pulmonary responsiveness to Mch in both types of normal mice (P < 0.0001 by analysis of variance) but not in either genotype of mast cell-deficient mouse. Additionally, anti-IgE pretreatment of genetically mast cell-deficient W/Wv mice whose mast cell deficiency had been repaired by infusion of freshly obtained bone marrow cells or bone marrow-derived cultured mast cells from congenic normal mice led to significant (P < 0.0001) enhancement of Mch responsiveness. 5-HT responsiveness was not significantly influenced by anti-IgE pretreatment in any of the mice studied. The data support the hypothesis that IgE-mediated activation of mast cells enhances pulmonary responsiveness to cholinergic stimulation.
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PMID:Mast cell activation enhances airway responsiveness to methacholine in the mouse. 845 46

In previous investigations we have shown that chemical allergens of different classes induce in mice qualitatively divergent immune responses. Respiratory allergens provoke substantial increases in total serum concentration of IgE. In contrast, contact allergens which are known or suspected not to cause respiratory sensitization or which at most have only a very limited potential to do so, have little or no effect on total serum IgE. Such differences, we propose, provide a novel approach for the prospective identification of chemicals with potential to cause respiratory allergy. In the absence of a robust method for the direct measurement of respiratory hypersensitivity reactions in mice we have sought in the present study to determine whether the IgE responses induced in mice by respiratory allergens are specific and of sufficient magnitude to cause the active sensitization of mast cells in vivo, a prerequisite for immediate hypersensitivity, including acute-onset respiratory hypersensitivity. Topical exposure of BALB/c mice to concentrations of > or = 10% of the human respiratory allergen trimellitic anhydride (TMA) caused the specific sensitization of peritoneal mast cells in situ as measured by the conjugate-induced release of [3H]-5-hydroxytryptamine in vitro. Experiments were performed also with 2,4-dinitrochlorobenzene (DNCB), a contact allergen that fails to induce respiratory hypersensitivity. Treatment of mice with concentrations of DNCB of comparable immunogenicity failed to cause mast cell sensitization. These data demonstrate that a known human chemical respiratory allergen induces in mice specific mast-cell-sensitizing IgE antibody and reinforce the value of the mouse as a model for the evaluation of respiratory sensitization potential.
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PMID:Induction of mast cell sensitization by chemical allergens: a comparative study. 848 12

In order to investigate the functional similarities of the high affinity receptor for IgE (Fc epsilon RI) and the T cell receptor for antigen, we have developed a high efficiency polyethylene glycol-mediated fusion method to make somatic hybrids between cells from a mast cell line (RBL-2H3) and cells from T lymphoma cell lines (Jurkat and HPB-ALL). Using flow cytometry to select for the heterologously fused cells, we demonstrated that aggregation of the T cell receptor results in the efficient secretion of [3H]5-hydroxytryptamine from RBL cell-derived granules. In addition, both receptors mediate Ca2+ mobilization in the hybrid cells that is insensitive to inhibition by the protein kinase C activator phorbol-12-myristoyl-13-acetate (PMA). In contrast, Ca2+ mobilization caused by aggregation of Fc epsilon RI in the parent RBL cells is completely inhibited by PMA. The results indicate that these two different receptors for foreign antigen can substitute for each other to trigger responses in the hybrid cells that are unique to each cell type. The methodology employed has general utility for studying signal transduction mediated by mammalian cell surface receptors.
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PMID:Fc epsilon RI and the T cell receptor for antigen activate similar signalling pathways in T cell-RBL cell hybrids. 849 25

Many of the airway responses to endogenous and exogenous stimuli are caused by indirect mechanisms such as the activation of neurons and/or inflammatory cells. In the present study we compare the bronchoconstrictor and the plasma protein extravasation response to adenosine and tachykinins in two highly inbred rat strains, F344 and BDE. BDE-rats have a bronchoconstrictor response to adenosine at lower doses. Challenge with the A3-adenosine receptor agonist APNEA demonstrates that the difference in airway responsiveness to adenosine between BDE- and F344-rats is probably related to a higher number of A3-receptors on the airway mast cells of BDE-rats. In contrast, F344-rats have a higher airway responsiveness to tachykinins than BDE-rats. Tachykinins cause bronchoconstriction in F344-rats mainly by an indirect mechanism, involving stimulation of NK1-receptors and mast cell activation. In BDE-rats they cause bronchoconstriction by a direct effect on airway smooth muscle via activation of NK2-receptors. Finally we also observed a difference between F344- and BDE-rats with regard to the mechanisms involved in the plasma protein extravasation in the airways caused by substance P or capsaicin. In F344-rats but not in BDE-rats mast cell activation and the release of 5-hydroxytryptamine is partly responsible for this plasma protein extravasation.
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PMID:Genetic control of indirect airway responsiveness in the rat. 859 Mar 45


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