Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mast cells are present in proximity to the microvessels, and on stimulation with inhibition of NO synthesis, are a rich source of numerous inflammatory mediators. A microcirculatory study was undertaken to clarify whether nitric oxide (NO) and activation of guanylate cyclase is involved in degranulation of perivascular mast cells in the rat mesenteric venule, and whether oral administration of ketotifen suppress the degranulation. Intravital microscopy was used to monitor the rates of adherence and extravasation of leukocytes in single unbranched venules with diameters between 25 and 35 microm of rat mesentery. Leukocyte rolling velocity, red blood cell velocity, vessel diameter and blood pressure were also measured. Mast cell degranulation was quantified within 30 microm from the venule. NG-nitro-L-arginine methyl ester (L-NAME) at an intravenous dose of 30 mg kg-1 increased the number of degranulated cells, while its enantiomer, D-NAME at the same dose had no effect. Superfusion with methylene blue (MB), an inhibitor of soluble guanylate cyclase, at 50 microm elicited similar degranulation of the mast cells. The degranulation was associated with increased adhesion of leukocytes to the endothelium and the slowed rolling. Pretreatment with ketotifen at an oral dose of 1 mg kg-1 inhibited mast cell degranulation in responses to either L-NAME or MB. It is conceivable that guanylate cyclase for NO production pathway in endothelial and/or mast cells is involved in the mast cell degranulation process, and the process or subsequent action of NO may be preserved by ketotifen, eliciting down-modulation of mast cell activation.
 ...
PMID:Mast cell degranulation in rat mesenteric venule: effects of L-NAME, methylene blue and ketotifen. 1032 98

We investigated the effect of sodium nitroprusside (SNP), a donor of nitric oxide, on the formation of platelet-activating factor (PAF) and uterine contractility in mouse uterine horns from mice treated with estrogen. Because the major pathway of PAF synthesis is the remodeling pathway in uterine tissue, we evaluated the incorporation of 14C-acetate into PAF-like molecules. Our results showed that SNP (100-300 mumol/L) caused a transient increase in the synthesis of PAF, which remained cell-associated. The addition of SNP (100-300 mumol/L) to a mouse uterine horn in an isolated organ bath preparation evoked a transient increase in contractility, which was inhibited by hemoglobin (2 micrograms/mL), a nitric oxide scavenger, but not by methylene blue (10 mumol/L), a guanylate cyclase inhibitor. The pharmacological characteristics of the contractions evoked by SNP resembled those evoked after mast cell activation, in that they were blocked by ritodrine (a beta 2 adrenergic agonist, 0.1 mumol/L); indomethacin (a cyclooxygenase inhibitor, 10 mumol/L); ketotifen (a mast cell stabilizer, 1.0 mumol/L); cromolyn sodium (a mast cell stabilizer, 100 mumol/L); pyrilamine (an H1 antagonist, 10 mumol/L); and ketanserine (5HT2 antagonist, 0.1 mumol/L). These data demonstrate that nitric oxide generated from SNP stimulated the synthesis of PAF and evoked contractility in uterine horns from mice treated with estrogen. This result suggests the possibility that these tissue conditions might be favorable for the generation of peroxynitrites, possible mediators of both effects. It is also shown that the contractility evoked by the addition of SNP was not due to production of PAF, because its antagonist, WEB 2086 (10-30 mumol/L, a concentration that blocked contractions evoked by PAF 1 nmol/L), had no effect on the SNP-evoked contractions.
 ...
PMID:Nitroprusside stimulates contractility and the synthesis of 14C-acetylated PAF-like substances in estrogen primed-mouse uterine horns. 1036 96

The effect of a thrombin receptor agonist peptide (TRAP-6) on the release of nitric oxide (NO) and platelet activating factor (PAF) from resting and calcium-ionophore (A23187)-activated rat peritoneal mast cells (RPMC) was studied using a platelet aggregation bioassay. RPMC spontaneously released NO, which inhibited TRAP-6-, ADP-, and PAF-stimulated platelet aggregation. This effect of NO was abolished by the addition of an NO binding agent, oxyhemoglobin (oxyHb), to the platelet suspension. The RPMC-induced suppression of platelet aggregation was completely inhibited by the NO-synthase inhibitor L-NAME. TRAP-6 and its high affinity analog haTRAP stimulated the rapid release of NO from RPMC. The effect of TRAP-6 was inhibited by pretreatment of the RPMC with L-NAME or with the inhibitor of the constitutive NO-synthase isoform (cNOS) calmidazolium. TRAP-6 inhibited PAF release from A23187-activated RPMC via an NO-dependent mechanism. Platelet aggregation induced by PAF release from activated RPMC was also confirmed in experiments using the PAF receptor antagonist ginkgolide B. Thus, TRAP-6 is a rapidly acting modulator of mast cell reactivity; it stimulates NO release and inhibits PAF secretion.
 ...
PMID:Modulation of mast cell activity by a peptide agonist of the thrombin receptor: role of nitric oxide. 1039 81

Interferon-gamma (IFN-gamma) is an important regulatory cytokine in cell proliferation, differentiation, adhesion, mediator release, and gene induction. This diversity of effector roles is achieved by a variety of incompletely understood mechanisms. In the mast cell (MC), IFN-gamma downregulates mediator synthesis and secretion. The present study demonstrates and characterizes for the first time IFN-gamma inhibition of adhesion of the MC analogue RBL-2H3 to the extracellular matrix protein fibronectin (FN). Inhibition requires preincubation of the cells with IFN-gamma for 20 hr, and is statistically significant at 100 U/ml IFN-gamma. Flow cytometry indicates that cell surface expression of very late antigen-4 (VLA-4), VLA-5, and the vitronectin receptor (VNR) remain constant following IFN-gamma treatment, indicating the inhibitory effect of IFN-gamma on adhesion to FN is not achieved through a reduction in integrin receptors for FN. Fluorescent labelling with Texas red phalloidin demonstrated rearrangement of the actin cytoskeleton in response to IFN-gamma was not significant. The tyrosine phosphatase inhibitor vanadate, and the nitric oxide (NO) synthase inhibitor L-NAME, reduced the IFN-gamma effect on adhesion to FN by 62 and 70%, respectively, demonstrating that the IFN-gamma effect is dependent upon the production of NO, potentially though a tyrosine phosphatase dependent mechanism. The NO donors sodium nitroprusside and S-nitrosoglutathione mimicked the effect of IFN-gamma. Thus, following stimulation with IFN-gamma, NO plays an autocrine role in the MC, and is able to modulate integrin function. This adds to the pathways NO is able to inhibit in the mast cell, shows that endogenous NO is able to inhibit these pathways, and suggests NO is impinging upon an element common to many signalling mechanisms in the MC.
 ...
PMID:Interferon-gamma regulates the interaction of RBL-2H3 cells with fibronectin through production of nitric oxide. 1044 71

In the present study, we have observed the development of an inflammatory reaction in the rat hindpaw, following the injection of specific agonists of PAR2 (two PAR2 activating peptides). This inflammation was characterized by oedema and granulocyte infiltration. Two selective PAR2 activating peptides, SLGRL-NH2 and trans-cinnamoyl-LIGRLO-NH2 induced significant oedema in the rat hindpaw from 1-6 h following subplantar injection. Six hours after the PAR2-activating peptide injection, the paw tissues showed a complete disruption of tissue architecture along with an inflammatory cell infiltrate. In the inflamed paw, PAR2-immunoreactivity was expressed on endothelial cells as well as on the infiltrating inflammatory cells. The oedema induced by the injection of the two PAR2 activating peptides was slightly reduced in rats pre-treated with compound 48/80, but was not modified by pre-treatment of rats with cromolyn, a mast cell stabilizer. Pre-treatment of rats with a cyclo-oxygenase inhibitor (indomethacin) or a nitric oxide synthase inhibitor (L-N(omega)-nitro-L-arginine methyl ester) had no effect on the oedema induced by the PAR2-activating peptides. These results demonstrate that the administration of PAR2-activating peptides into the rat paw induced an acute inflammatory response characterized by a persistent oedema (at least 6 h) and granulocyte infiltration. The PAR2-induced inflammatory response occurred through a mechanism largely independent of mast cell activation, and of the production of prostanoids and nitric oxide.
 ...
PMID:Characterization of the inflammatory response to proteinase-activated receptor-2 (PAR2)-activating peptides in the rat paw. 1045 52

Our study is designed to correlate nitrite concentration, an index of nitric oxide (NO) release with mast cell peroxidase (MPO), a marker of cardiac mast cell degranulation and cardioprotective effect of ischaemic preconditioning in isolated perfused rat heart subjected to 30 min of global ischaemia and 30 min of reperfusion. Ischaemic preconditioning, comprised of four episodes of 5 min global ischaemia and 5 min of reperfusion, markedly reduced the release of lactate dehydrogenase (LDH) and creatine kinase (CK) in coronary effluent and incidence of ventricular premature beats (VPBs) and ventricular tachycardia and fibrillation (VT/VF) during reperfusion phase. Ischaemia-reperfusion induced release of MPO was markedly reduced in ischaemic preconditioned hearts. Increased release of nitrite was noted during reperfusion phase after sustained ischaemia in preconditioned hearts as compared to control hearts. No alterations in the release of nitrite was observed immediately after ischaemic preconditioning. However, ischaemic preconditioning markedly increased the release of MPO prior to global ischaemia. It is proposed that cardioprotective and antiarrhythmic effect of ischaemic preconditioning may be ascribed to degranulation of cardiac mast cells. Depletion of cytotoxic mediators during ischaemic preconditioning and consequent decreased release of these mediators during sustained ischaemia-reperfusion may be associated with preservation of structures in isolated rat heart responsible for NO release.
 ...
PMID:Possible role of cardiac mast cell degranulation and preservation of nitric oxide release in isolated rat heart subjected to ischaemic preconditioning. 1054 45

Sulfasalazine and 5-aminosalicylic acid are very useful therapeutic agents for the treatment of the inflammatory bowel disease, such as ulcerative colitis or Crohn's disease. However, the mechanism of action of the aminosalicylates remains obscure. Recently, many studies about their mechanism have been performed. As a result, aminosalicylates have been identified to have several antiinflammatory pathways: (1) alterations in eicosanoid metabolism of arachidonic acid; particularly inhibition of leukotrien B4 production, (2)free radical scavengers; scavenging reactive oxygen metabolites or nitric oxide (3)immunologic suppression; inhibition of HLA-DR expression on the intestinal epithelial cells, inflammatory cytokine(IL-1 and IL-2) production, adhesion molecule expression, platelet-activating factor release, or histamine release from mast cell, and so on.
 ...
PMID:[Salazosulfapyridine and 5-aminosalicylic acid agents for the treatment of ulcerative colitis]. 1057 15

Vasoactive intestinal peptide (VIP) has potent protective activity against sepsis and increases the survival rate of septic rats and mice. The present study was planned to evaluate the effect of VIP on mast cell activity, histamine and methylhistamine levels and oxidative stress in the liver and kidneys of septic rats. The effect of VIP was compared to that of nitric oxide synthesis inhibition, previously tested extensively in septic shock models, with doubtful benefit. The present study showed that endotoxic shock did not lead to oxidative stress in either liver or kidney of the rats. On the other hand, mast cells, based on their location, displayed functional heterogeneity to the septic insults. VIP possibly modulated the specific reactions of the tissues to mediators released from mast cells during septic shock. The most prominent effect of VIP as compared to nitric oxide synthesis inhibition was related to mast cells. In conclusion, the prevention of mast cell reactivity by VIP could be a potential therapeutic strategy in controlling septic shock.
 ...
PMID:Vasoactive intestinal peptide inhibits degranulation and changes granular content of mast cells: a potential therapeutic strategy in controlling septic shock. 1070 23

The present article overviews the regulatory mechanism of acid secretion in the stomach after damage with taurocholate (TC), one of the bile acids. Mucosal exposure of a rat stomach to 20 mmol/L TC for 30 min caused a decrease of acid secretion with a concomitant increase in nitric oxide (NO) and prostaglandin (PG) E2 (PGE2) as well as Ca2+ in the luminal contents. Prior administration of N(G)-nitro-L-arginine methyl ester (L-NAME), as well as indomethacin, significantly attenuated the reduction of acid secretion by TC and acid secretion was even increased in the presence of L-NAME. The acid stimulatory effect of L-NAME in the damaged stomach was not mimicked by aminoguanidine and was antagonized by co-administration of L-arginine but not D-arginine. Increased NO release in the damaged stomach was suppressed by pretreatment with L-NAME or co-application of EGTA and the latter also inhibited the increase in luminal Ca2+. The enhanced acid secretory response in the presence of L-NAME was also inhibited by cimetidine, FPL-52694 (a mast cell stabilizer) or sensory deafferentation. Mucosal exposure to TC caused an increase in luminal histamine output, together with a decrease in the number of mucosal mast cells in the stomach. These changes were prevented by FPL-52694 and sensory deafferentation and were also partly suppressed by indomethacin. In addition, the acid stimulatory action of L-NAME in the damaged stomach was significantly mitigated when indomethacin was administered together with L-NAME. We conclude that: (i) damage in the stomach may activate acid a stimulatory pathway in addition to a PG-, NO- and Ca2+-dependent inhibitory mechanism, but the latter effect overcomes the former, resulting in a decrease in acid secretion; (ii) acid stimulation in the damaged stomach is mediated by histamine released from the mucosal mast cell, a process interacting with capsaicin-sensitive sensory nerves; (iii) the increase in luminal Ca2+ plays a role in increasing NO production and, hence, in regulating acid secretion; and (iv) PG may have a dual role in the regulation of acid secretion in the damaged stomach: an inhibitory effect at the parietal cell and an excitatory effect, probably through enhancing the release of mucosal histamine.
 ...
PMID:Regulatory mechanism of acid secretion in the damaged stomach: role of endogenous nitric oxide. 1075 19

The exact mechanisms by which Helicobacter pylori infection results in gastric mucosal injury are unclear. However, it has been demonstrated that surface protein extracts of the bacterium can induce a number of disturbances within the rat gastric mucosal microcirculation, including platelet aggregation and macromolecular leakage (MML) of labeled albumin. This study aimed to determine the mechanisms involved in inducing these events using the technique of fluorescent in vivo microscopy. Male Wistar rats were pretreated with either ketotifen, a mast cell stabilizer (1 mg/kg), pyrilamine, an H1-receptor antagonist (30 mg/kg), hexanolamine-PAF, a PAF-receptor antagonist (10 microg/kg), L-arginine, the nitric oxide precursor (300 mg/kg) or vehicle, saline. Then 0.5 ml of H. pylori extract was administered to the exteriorized gastric mucosa of the anesthetized rat. Alterations in fluorescein-labeled albumin leak, vessel diameters, and acridine red-labeled leukocyte and platelet activity were determined over a 2-hr period. Saline pretreated animals demonstrated significant MML with a peak at 5 min (11%, P<0.02). This was prevented with ketotifen and pyrilamine, but not with hexanolamine-PAF (17.5%, P<0.05) and L-arginine (13%, P<0.05). Significant numbers of platelet emboli and thrombi were observed within mucosal capillaries and postcapillary venules with vehicle pretreatment; this was prevented with hexanolamine-PAF and L-arginine, but not with ketotifen and pyrilamine. In conclusion, these studies demonstrate that more than one mediator is involved in inducing the rat gastric mucosal microcirculatory disturbances associated with H. pylori administration. Mast cells and histamine are linked to MML, with PAF, probably not derived from mast cells, involved in platelet activation.
 ...
PMID:Mechanisms of Helicobacter pylori-induced rat gastric mucosal microcirculatory disturbances in vivo. 1075 48


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>