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)

Induction of anaphylactic shock in mice by i.v. antigen challenge (bovine serum albumin, 100 micrograms) or i.v. treatment with the mast cell degranulator compound 48/80 resulted in 80 and 90% mortality rate, respectively. Inhibition of nitric oxide (NO) synthesis from L-arginine by co-injection of the L-arginine analog NG-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg) reduced the mortality rate by 40 and 20% in the antigen- and compound 48/80-induced shock models. Treatment with 60 mg/kg L-NAME reduced the mortality rate by 60% in these shock models. This beneficial effect was reversed by addition of L-arginine (120 mg/kg) but not D-arginine (120 mg/kg). These results suggest NO production as a possible mechanism involved in the pathophysiology of anaphylactic shock.
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PMID:An inhibitor of nitric oxide production, NG-nitro-L-arginine-methyl ester, improves survival in anaphylactic shock. 179 50

An association was found in rats of different strains between the susceptibility to EAU and the number of mast cells in the choroid of the eye. High responder rats (Lewis, CAR) had strikingly more choroidal mast cells than the low responder BN animals, whereas intermediate numbers of mast cells were found in the F1 hybrids of Lewis and BN (LBNF), which exhibited an average level of susceptibility to EAU. LeR rats, derived from the Lewis strain, developed EAU only when treated with B. pertussis, and their number of choroidal mast cells was only about 1/5 of that found in the Lewis rats. Unlike the differences in the number of choroidal mast cells, small variations were found in the skin mast cell numbers of the tested rats. It is proposed that the number of local mast cells may be one mechanism by which the susceptibility to an organ-specific autoimmune disease is genetically regulated.
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PMID:An association between susceptibility to experimental autoimmune uveitis and choroidal mast cell numbers. 633 30

Photoactivation of intravascular dyes with high doses of light is a technique used clinically to treat tumors. This procedure results in arteriolar constriction, mast cell degranulation, platelet thrombus formation, and, ultimately, microvascular stasis. In vivo microscopy was utilized in the current study to examine if the endothelial release of prostaglandins and nitric oxide could participate in the microvascular effects of photoactivation. Diameter changes and thrombus formation of arterioles and venules of the cremaster muscle of male Sprague-Dawley rats were quantitated during continuous light activation of intravascular fluorescein isothiocyanate conjugated to bovine serum albumin. Vasoconstriction and thrombus development were assessed separately, using the relationships between the width of the red blood cell column, the inner wall diameter, and the thickness of the plasma layer. Venular photoactivation resulted in thrombus growth which reached 30% of the maximum size by 16.8 +/- 3.71 min and a subsequent growth rate of 6.2 +/- 1.64 microns/min. In arterioles, 30% thrombus growth occurred at 14.0 +/- 2.02 min with a growth rate of 3.0 +/- 0.57 microns/min. Continuous arteriolar photoactivation led to a vasoconstriction of 34.4 +/- 6.87% of the initial vessel diameter. Thirty percent of the maximal constriction occurred after 10.6 +/- 1.26 min of photoactivation. Constriction proceeded at a rate of 3.8 +/- 1.32 microns/min. Topically applied mefenamic acid (a cyclooxygenase inhibitor) and Nw-nitro-L-arginine methyl ester (L-NAME, a nitric oxide synthase inhibitor) each enhanced both the arteriolar and the venular thrombus growth due to photoactivation. Photoactivation-induced arteriolar constriction was augmented by L-NAME and inhibited by mefenamic acid. These data suggest that the photoactivation of intravascular dyes is accompanied both by the release of nitric oxide, which inhibits thrombus development and arteriolar constriction, and by the release of cyclooxygenase products, which inhibit thrombus growth and induce vasoconstriction. Rats treated with busulfan to induce thrombocytopenia exhibited a 90% decrease in circulating platelets. In these animals, photoactivation caused significantly delayed thrombus growth in arterioles and venules, while arteriolar constriction remained unaltered, suggesting that the vasoconstrictor prostanoid is not of platelet origin.
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PMID:Involvement of nitric oxide and cyclooxygenase products in photoactivation-induced microvascular occlusion. 751 91

The objective of this study was to determine whether an inhibitor of nitric oxide (NO) synthase (NG,NG'-dimethyl-L-arginine; L-DMA) that is produced by vascular endothelium elicits the inflammatory responses induced by synthetic analogues of L-arginine such as NG-nitro-L-arginine methyl ester (L-NAME). Leukocyte adherence and emigration, leukocyte-platelet aggregation, and albumin leakage were monitored in rat mesenteric venules exposed to different concentrations of either L-DMA or L-NAME. Increases in leukocyte adherence (7- to 9-fold) and emigration (3- to 5-fold), platelet-leukocyte aggregation, mast cell degranulation, and an enhanced albumin leakage (30-50%) were observed within 30 min after exposing the microvascular bed to either inhibitor; however, leukocyte emigration and albumin leakage responded more intensely to L-NAME than to L-DMA. The microvascular alterations and mast cell degranulation were attenuated by addition of L-arginine to the superfusate. These results suggest that the L-DMA is capable of eliciting an inflammatory response at concentrations detected in plasma under certain pathological conditions.
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PMID:Effects of an endogenous inhibitor of nitric oxide synthesis on postcapillary venules. 754 59

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

We have investigated the contractile effect of bradykinin (BK) in guinea pig lung in vitro. BK induces a dose-related contraction of lung parenchymal strips which is increased significantly in the presence of 10(-5) M captopril (an angiotensin converting enzyme inhibitor) or 10(-5) M DL-thiorphan (a neutral endopeptidase inhibitor). The kininase I inhibitor, DL-2-mercaptomethyl-3-guanidino-ethylthiopropionic acid (MGTPA), has no effect on the BK-induced contraction. BK is more potent in contracting parenchymal lung strips than other contractile agents (histamine, carbachol and substance P), however the BK-induced maximal contraction is lower than those obtained with histamine and carbachol. The B1 agonist, des-Arg9-BK, does not contract lung parenchymal strips. The new BK B2 receptor antagonists (Hoe 140, NPC 17731 and NPC 17761), which possess binding affinities in the nanomolar range, inhibit the BK-induced contractile response in a dose-dependent manner. The BK-induced contraction was unaffected by propranolol, atropine, tetrodotoxin, capsaicin pre-treatment, triprolidine, methysergide, Ro 19-3704 and N omega-nitro-L-arginine-methyl-ester (L-NAME), excluding the involvement of nervous pathways, preformed mast cell mediators, platelet-activating factor and nitric oxide. However, indomethacin, a cyclooxygenase inhibitor, AA-861, a 5-lipoxygenase inhibitor, and furegrelate, a thromboxane A2 synthase inhibitor, decreased the contractile response to BK, suggesting that both cyclooxygenase and 5-lipoxygenase products are involved in this contraction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bradykinin-induced contraction of guinea pig lung in vitro. 799 Sep 78

Treatment 20 min beforehand with an inhibitor of nitric oxide (NO) synthesis NW-nitro-1-arginine methyl ester (L-NAME) (12.5, 25, 50 or 100 mg/kg, s.c.), dose-dependently intensified gastric glandular mucosal ulceration produced by cold-restraint stress. Hexamethonium (20 mg/kg) or atropine (1 mg/kg) pretreatment s.c. 20 min before stress strongly antagonised stress-evoked ulceration, as well as the ulcer-potentiating effects of L-NAME when either cholinoceptor antagonist was given concurrently with the NO inhibitor. Stress-induced mast cell degranulation was not worsened by L-NAME pretreatment. The findings suggest that NO could confer partial protection against stress-induced gastric ulcer formation; its activity is triggered off by the ulcerogenic mechanism of stress.
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PMID:Nitric oxide inhibition intensifies cold-restraint induced gastric ulcers in rats. 809 77

In this study, we assessed the involvement of mast cells and mast cell-derived mediators in the enhanced epithelial permeability associated with nitric oxide synthesis inhibition. Permeability of the small bowel was assessed by measuring the clearance of a small marker (51Cr-labeled EDTA) from blood to lumen in the presence of the nitric oxide synthesis inhibitor, NG-nitro-L-arginine methyl ester (L-NAME). L-NAME caused a very rapid (10 min) increase in epithelial permeability, reaching peak values (sixfold increase) within 20 min. Two mast cell stabilizers, doxantrazole and lodoxamide, greatly attenuated the rise in mucosal permeability. Rat mast cell protease II activity (marker of mucosal mast cell degranulation) was increased significantly only in the plasma of L-NAME-treated animals. Chronic dexamethasone administration depleted rats of mucosal mast cells and also prevented the L-NAME-induced rise in mucosal permeability. The increase in epithelial permeability was mediated by a number of mediators: platelet-activating factor caused the early rise in epithelial permeability, and histamine caused the later increase in epithelial permeability. Superoxide dismutase attenuated the L-NAME-induced rise in epithelial permeability, suggesting an important and continuous role for superoxide. Transepithelial flux of 51Cr-EDTA across rat intestinal epithelial cell monolayers did not increase in the presence of L-NAME, suggesting that inhibition of nitric oxide does not directly cause epithelial permeability alterations, whereas the in vivo data implicate a potential role for the mast cell. In conclusion, nitric oxide synthesis inhibition activates mast cells in the mucosa and consequently increases epithelial permeability.
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PMID:Nitric oxide synthesis inhibition increases epithelial permeability via mast cells. 814 Dec 95

Release of inflammatory mediators by mast cells can be modulated by certain cytokines and by nitric oxide. An in vitro platelet aggregation bioassay was used to assess the effects of interleukin-1 beta (IL-1 beta) on the release of platelet-activating factor and nitric oxide from resting or ionophore-activated peritoneal mast cells (PMC) from rat. PMC spontaneously released a substance that inhibits thrombin-stimulated platelet aggregation. The activity of this substance is abolished by addition of hemoglobin to the platelet suspension and augmented by preincubation of the PMC with L-arginine, suggesting that it is nitric oxide. Within minutes, IL-1 beta concentration-dependently (1 pg/ml-100 ng/ml) enhanced the release from activated PMC of nitric oxide, as measured by its ability to inhibit thrombin-induced platelet aggregation, and as confirmed with a biochemical assay for nitrite. This action of IL-1 beta was inhibited by pretreatment of PMC with a calmodulin antagonist (calmidazolium), an IL-1 receptor antagonist, or either of two nitric oxide synthase inhibitors (L-NAME and LY-83583). IL-1 beta also inhibited the release of platelet-activating factor from PMC through a nitric-oxide-dependent mechanism. These results demonstrate that IL-1 beta is a potent and rapid-acting modulator of mast cell reactivity, stimulating nitric oxide release while inhibiting the production of platelet-activating factor.
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PMID:Modulation of rat mast cell reactivity by IL-1 beta. Divergent effects on nitric oxide and platelet-activating factor release. 839 60

Recent work has demonstrated that inhibition of nitric oxide production with various nitric oxide synthesis inhibitors (L-NAME, L-NMMA) initiate leukocyte adhesion to postcapillary venules. The objective of this study was to elucidate the mechanism (or mechanisms) that promote the L-NAME-induced leukocyte response. Intravital microscopy was used to examine 25-40 microns venules in the rat mesentery. Nitric oxide synthesis was inhibited with L-NAME and leukocyte adhesion was observed over the first 60 min. The fourfold increase in leukocyte adhesion was independent of alterations in venular red blood cell velocity. The adhesion was superoxide-mediated inasmuch as superoxide dismutase (SOD) abolished the rise in leukocyte adhesion associated with nitric oxide synthesis inhibition. Ketotifen, a mast cell stabilizer, also abolished the rise in leukocyte adhesion induced by L-NAME. Histology revealed that mast cell degranulation occurred only in animals treated with L-NAME but not in animals pretreated with SOD or ketotifen. This observation suggests that mast cells become activated in the absence of nitric oxide production and superoxide contributes to the mast cell activation. The L-NAME-induced leukocyte adhesion could be reproduced by infusing hypoxanthine/xanthine oxidase (a superoxide generating system) or compound 48/80 (an activator of mast cells) and both responses were attenuated by ketotifen. These data suggest that inhibition of nitric oxide synthesis results in a superoxide and mast cell-dependent leukocyte adhesion.
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PMID:Nitric oxide synthesis inhibition induces leukocyte adhesion via superoxide and mast cells. 840 15


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