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)

The effect of some gastroprotective agents cysteamine, sodium salicylate, atropine, cimetidine, and pyrido-pyrimidine derivatives, rimazolium, Ch-127 and a mast cell stabilizer, BMY-26517-31 was studied on the enhanced vascular permeability of gastric mucosa induced by 100% ethanol, on the enhanced vascular permeability of peritoneal blood vessels due to 0.3% acetic acid and on carrageenin edema test. We found that cysteamine, sodium salicylate, rimazolium and BMY-26517-31 inhibited the alcohol-induced enhanced vascular permeability. They also decreased the carrageenin-induced edema and--with the exception of BMY-26517-31--the acetic-acid-induced enhanced vascular permeability of the peritoneal vessels. These results suggest that similar events are present in the early phase of acute inflammation and chemically induced mucosal lesions. Consequently, antiinflammatory activity might play role in the protective mechanism of some anti-ulcer agents.
 ...
PMID:The effect of some anti-ulcer agents on the early vascular injury of gastric mucosa induced by ethanol in rats. 259 6

Mast cells were visualized in stretch preparations of the rat dura mater and were found mostly in relation to small and large blood vessels. The overall number of dural mast cells was unaffected by electrical trigeminal or chemical deafferentation. As in other tissues, mast cell degranulation increased at sites of local injury (electrode penetration) or after systemic treatment with compound 48/80. However, mast cells did not degranulate following electrical trigeminal stimulation, or after injection of drugs (capsaicin or substance P) which promote plasma extravasation in the dura. Furthermore, pretreatment with a mast cell stabilizer (sodium dicromoglycate) or with large doses of H1 and H2 histamine receptor blockers (mepyramine and cimetidine), did not block electrically- or chemically-induced neurogenic plasma extravasation (NPE). Daily pretreatment with 48/80 however completely attenuated or abolished NPE. Taken together these data suggest that as assessed by the extrusion of metachromatic granules, mast cells are not essential to the development of neurogenic inflammation within the rat dura mater. However, these findings cannot exclude the possibility that mast cells may amplify or modulate this process.
 ...
PMID:The development of neurogenic plasma extravasation in the rat dura mater does not depend upon the degranulation of mast cells. 270 81

An in vivo model of the rat urinary bladder microcirculation has been developed and microcirculatory responses to agents which produce vasoconstriction, vasodilation, and macromolecular leakage have been characterized. The urinary bladder of anesthetized female Sprague-Dawley rats is exteriorized and positioned in a tissue bath with a single stay suture which does not penetrate the lumen of the bladder. All blood vessels and nerves from the animal remain intact. The tissue bath is filled with Krebs solution which is monitored and maintained at a temperature of 36 +/- 0.5 degrees and a pH of 7.4 +/- 0.5. In vivo television microscopy is used to monitor vascular diameter and flow changes and isothiocyanate-tagged bovine serum albumin fluorescence is used as an index of macromolecular leakage. Norepinephrine (10(-6) M) caused a statistically significant decrease in vascular diameters of both arterioles and venules while sodium nitroprusside (10(-7) M) significantly increased arteriolar and venular diameters, histamine (10(-4) M) caused no change in venular diameters but did induce a significant macromolecular leak from those vessels. Compound 48/80 (1 and 10 micrograms/ml) induced a significant dose-dependent macromolecular leakage from venules. However, only with the 10 micrograms/ml dose was there visually detectable mast cell degranulation. It is concluded that this rat urinary bladder model provides a stable, reproducible model of a smooth muscle microcirculatory bed in a controlled environment, which responds similarly to other microcirculations.
 ...
PMID:The rat urinary bladder: vasoactivity and macromolecular leakage in a new model. 276 31

Injection of zymosan in rat pleural cavity provokes an exudate which is already detectable at 15 min and which is maximum at 24 h. The leucocyte count (mostly neutrophils) increases at 2-4 h and is maximum at 48 h. In this paper the reaction has been studied up to 6 h. Evidence of histamine release, of mast cell degranulation and of reduction of the exudate by anti-H1 compounds, as well as by sodium cromoglycate, proves the active role played by histamine in the early stage of pleurisy. Serotonin (whose role was studied exclusively using antagonists) seems to have only a minor part in the early phase of the reaction. Some metabolites of arachidonic acid were determined in the pleural exudate at 1 h and 6 h. The concentration of leukotriene B4 was high at 1 h and decreased at 6 h. The thromboxane B2 level was already high at 1 h and was neatly augmented at 6 h while the amount of prostaglandin F1 alpha was high at both times. The non-steroidal anti-inflammatory substances studied all reduced the pleural exudate at 1 h but their activity then varied from each other at 6 h. Cyclooxygenase and lipoxygenase inhibitors (phenidone, BW755C) induced a reduction of the exudate at both times. Zymosan-induced pleurisy seemed thus to be an excellent model for the investigation of antiallergic and anti-inflammatory compounds active on histamine and cyclooxygenase and lipoxygenase pathways.
 ...
PMID:Pharmacological studies on zymosan inflammation in rats and mice. 2: Zymosan-induced pleurisy in rats. 277 57

The demonstration of a specific receptor for IgE on nonmast cell or basophil leukocytes, such as mononuclear phagocytes, eosinophils, and platelets, suggests that these cells may participate directly in immunological disorders of allergy. Thus, a full understanding of the mode of action of antiallergic or antiasthma drugs must take into account their activity on these nonmast cell leukocytes. Consequently, inhibition by nedocromil sodium of IgE-dependent activation of human alveolar macrophages, blood monocytes and platelets, was investigated. This compound induced an inhibition of the IgE-mediated generation of cytotoxic molecules from monocytes and platelets, together with a concomitant inhibition of their oxidative metabolism, measured by chemiluminescence, and a reduction of the potential ability of alveolar macrophages to synthesize and release mediators, estimated by lysosomal beta-glucuronidase activity. These observations confirm the hypothesis that nedocromil sodium acts on a cell compartment other than the classical mast cell population, in IgE-dependent allergy and, more particularly, in asthma.
 ...
PMID:Inhibition by nedocromil sodium of IgE-mediated activation of human mononuclear phagocytes and platelets in allergy. 282 42

In the present study some properties of an inhibitory extract of synaptosomal membrane Na+, K+-ATPase were investigated. This extract (peak II) was prepared by gel filtration in Sephadex G-50 of a soluble fraction of the rat cerebral cortex. Ultrafiltration of peak II through Amicon membranes indicated that the inhibitor has a low MW (less than 1000). The inhibitory activity was not modified by heating in neutral pH at 95 degrees C for 20 min but it was destroyed by charring in acid pH at 200 degrees C for 120 min. The inhibitory activity decreased by incubation of peak II with carboxypeptidase A. These findings suggest that the factor responsible for the inhibition of Na+, K+-ATPase activity is probably a polypeptide. On the other hand, the inhibition was reverted by the chelators EDTA and EGTA, indicating the participation of an ionic compound as well. The increase of Mg2+ concentration during the enzyme assay did not increase the inhibition, indicating that the ion involved might not be vanadate. It is suggested that both a polypeptide and an ionic compound coparticipate in the inhibitory effect of peak II on Na+, K+-ATPase activity.
 ...
PMID:The inhibitory activity of a brain extract on synaptosomal Na+, K+-ATPase is sensitive to carboxypeptidase A and to chelating agents. 283 64

Nedocromil sodium and cromolyn (sodium cromoglycate) are prophylactic agents in asthma which were initially found to be inhibitors of mast cell activation. Recent evidence has suggested that their effects on granulocyte-mediated reactions may contribute to their therapeutic effects. Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor (TNF) enhance the activity of granulocytes in antibody-dependent cell-mediated cytotoxicity (ADCC). Preincubation of purified neutrophils or eosinophils with nedocromil sodium or cromolyn partially inhibited their ability to mediate ADCC when stimulated by GM-CSF or TNF. Preincubation with nedocromil sodium did not alter the ability of neutrophils to produce superoxide or release lysozyme in response to soluble or phagocytic stimuli, and GM-CSF-enhanced superoxide production triggered by chemotactic peptide was not altered in such drug-treated neutrophils. After nedocromil sodium treatment, neutrophils showed no consistent changes in TNF-stimulated adherence to either plastic culture wells or umbilical vein endothelium. These findings demonstrate that nedocromil sodium and cromolyn directly and selectively affect the function of granulocytes in vitro. While drug-treated granulocytes were impaired in immune-directed cytotoxicity stimulated by GM-CSF or TNF, activation of other granulocyte functions by the same stimuli was intact.
 ...
PMID:Nedocromil sodium and cromolyn (sodium cromoglycate) selectively inhibit antibody-dependent granulocyte-mediated cytotoxicity. 284 86

1. The L-type Ca2+ current was recorded in guinea-pig ventricular myocytes by the patch clamp technique in the whole-cell configuration. The modification of the current by intracellular application of proteases was studied. 2. During the first phase of action, trypsin, an endopeptidase, increased the amplitude of Ca2+ current about 3-fold. 3. Thereafter, there was a drastic slowing of the inactivation time course of the enhanced Ca2+ current. The half-time of inactivation increased from a control value of about 25 ms to values larger than 200 ms. 4. Cell dialysis with carboxypeptidase A, an exopeptidase, also enlarged the amplitude of Ca2+ current, but did not affect the kinetics of Ca2+ current. Leuaminopeptidase did not modify the Ca2+ current. 5. The hypothesis that Ca2+ channels are affected by the protease is supported by the fact that alterations of the extracellular Na+ or K+ concentration did not influence the modification of the membrane current. Another argument for the involvement of Ca2+ channels is that the modified membrane current could be blocked by inorganic and organic Ca2+ channel blockers (e.g. 10 microM-Cd2+, 100 microM-La3+ or 1 microM-D600). 6. Although the actions of trypsin and maximal concentrations of isoprenaline on the amplitude of the Ca2+ current were not additive, the slowing of inactivation by trypsin occurred independently from beta-adrenergic stimulation. 7. The effect of trypsin on the Ca2+ current could not be blocked by intracellular 5'-adenylyl-imidodiphosphate (AMP-PNP) or Rp-adenosine 3'5'-monothionophosphate (Rp-cAMPS), both of which are known to suppress the cyclic AMP-dependent phosphorylation of the Ca2+ channel. 8. It was concluded that trypsin may directly modify the membrane protein which forms the Ca2+ channel. Since the increment in peak Ca2+ current resembled the action of cyclic AMP-dependent phosphorylation, it may be related to the removal of a 'chemical' inactivation gate which is normally controlled by phosphorylation. The slowing of the time course of Ca2+ current inactivation by trypsin could be due to a modification of the voltage-dependent inactivation gate. Alternatively, the endopeptidase might remove an internal Ca2+ binding site normally responsible for Ca2+-dependent inactivation.
 ...
PMID:Modification of L-type calcium current by intracellularly applied trypsin in guinea-pig ventricular myocytes. 285 49

Our previous studies demonstrated that rats sensitized to egg albumin had reduced intestinal absorption of water and electrolytes in response to intraluminal antigen. The rapid onset of this effect and reduction in mucosal histamine and numbers of granulated mast cells in the lamina propria suggested a reaginic (IgE) mechanism involving mast cell mediators. In this study we examined the effect of antiallergic agents on the intestinal transport abnormalities in our model. Sensitized rats, 14 days after intraperitoneal injection of 10 micrograms of egg albumin plus alum had specific IgE serum titers greater than or equal to 1:64; control rats had no measurable IgE antibodies. Net fluxes of Na+, Cl-, and H2O were determined by in vivo perfusion during a 1-hour antigen-free period and then a 1-hour antigen period. Sodium cromoglycate, administered intravenously (20 mg/kg) or in the perfusate (5 X 10(-4) mol/L) failed to prevent mucosal mast cell degranulation as evidenced by histamine release or the decrease in absorption of H2O, Na+, and Cl- induced by antigen exposure. In contrast, 10(-3) mol/L of doxantrazole in the perfusate completely inhibited these changes. Histamine receptor antagonists, H1, diphenhydramine, or H2, cimetidine, in perfusates had no effect on the transport abnormalities. Our findings support a role for intestinal mucosal mast cells, but not connective tissue mast cells, in the pathogenesis of the intestinal dysfunction associated with mucosal IgE-mediated reactions to food proteins and suggest that mast cell mediators other than histamine are involved.
 ...
PMID:Transport abnormalities during intestinal anaphylaxis in the rat: effect of antiallergic agents. 286 97

The effect of pharmacologic agents on mast cell mediator release was investigated in vivo. Eight atopic asthmatic subjects with airways relatively unreactive to nonspecific stimuli (geometric mean PC20 methacholine, 4.0 mg/ml) underwent single-concentration allergen challenge before (control) or after inhaling albuterol 200 micrograms, cromolyn sodium 20 mg, or 0.9% sodium chloride placebo. Six of the same subjects also underwent allergen challenge after pretreatment with ipratropium bromide, 1 mg. Airway responses to pharmacologic agents and bronchial challenge were measured by change in both specific airway conductance (SGaw) and FEV1. Mast cell mediator release was monitored by serial change in plasma histamine and, in addition, serum neutrophil chemotactic factor (NCF) on the placebo, albuterol, and cromolyn sodium challenge days. Control and placebo allergen challenges were associated with repeatable mean maximal falls in SGaw (48.5 versus 49.6%) and FEV1 (25.7 versus 25.5%). The mean increments in plasma histamine were not significantly different on the control (0.17 to 0.44 ng/ml) or placebo challenge days (0.18 to 0.64 ng/ml), with maximal levels occurring 5 min after challenge. A sustained increase in NCF was identified on the placebo challenge day (155.0% above baseline). Pretreatment with albuterol abolished any significant bronchoconstriction, with mean maximal falls in SGaw and FEV1 after challenge of 7.5 and 1.4%, respectively. These changes in airway caliber were not associated with any significant increment in mean plasma histamine (0.17 to 0.22 ng/ml) or serum NCF (4.1% increase). Cromolyn sodium pretreatment, while attenuating the airway response, was still associated with significant falls in SGaw (22.7%) and FEV1 (7.3%) and increases in plasma histamine (0.18 to 0.27 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Influence of albuterol, cromolyn sodium and ipratropium bromide on the airway and circulating mediator responses to allergen bronchial provocation in asthma. 293 89


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