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)

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.
 ...
PMID:The pharmacological differences and similarities between stress- and ethanol-induced gastric mucosal damage. 144 49

Verapamil is a calcium channel blocker that inhibits mast cell degranulation, platelet aggregation, and neutrophil function and is a potent vasodilator. The efficacy of verapamil (20 mg/kg/day) to salvage a standard failing random skin flap in the rat was studied. In this study verapamil failed to benefit skin flap survival. The results are analyzed and presented.
 ...
PMID:Efficacy of verapamil in the salvage of failing random skin flaps. 322 3

Drug effects were studied on anaphylactic histamine release from rat mast cells sensitized in vitro with mouse IgE antibody. When histamine release was elicited by adding Ca-++ at various times after antigen-stimulation of sensitized cells in Ca++-free medium, the drugs to be tested were added shortly before each Ca++ addition. Quercetin was effective only when added before or immediately after antigen. Theophylline and disodium cromoglycate (DSCG) were active irrespective of the time interval between antigen and Ca++ addition. Verapamil was more effective when added before or simultaneously with antigen than when added later. When tested in the two-stage experiments, quercetin showed inhibition only in Stage 1 and verapamil was inhibitive primarily in Stage 1, while theophylline and DSCG wee only inhibitive in Stage 2. It seems that quercetin selectively and verapamil primarily act to block calcium-gate opening resulting from antigen-antibody interaction on the mast cell membrane, while theophylline and DSCG selectively inhibit the passage of calcium through open calcium channels.
 ...
PMID:Inhibition of anaphylactic histamine release from heterologously sensitized mast cells: differential effects of drugs which interfere with calcium influx. 617 8

Verapamil was found to be an effective inhibitor of isometric tension in in vitro, experimental anaphylaxis in guinea pig trachealis smooth muscle. The mean IC50 for protection studies was 2 X 10(-4) M; the drug was also effective as a bronchoreversal agent. The inhibitory effect of verapamil upon the initial rate of isometric muscle tension suggests an action beyond simple calcium channel inhibition. No inhibition of tracheal mast cell histamine release was observed. Verapamil was slightly more potent than theophylline in this in vitro anaphylactic model.
 ...
PMID:Effect of calcium antagonists in experimental asthma. 618 12

Because both degranulation of mast cells and contraction of airway smooth muscle are dependent upon the influx of calcium, a calcium blocking agent might modify allergic bronchoconstriction by at least these two mechanisms. We treated sheep allergic to Ascaris suum antigen with the calcium antagonist Verapamil prior to airway challenge with an aerosol of Ascaris suum antigen and also investigated the response without pretreatment. Aerosolized Ascaris suum antigen increased mean pulmonary resistance (RL) to 530% of baseline (n = 6). Pretreatment with intravenously administered Verapamil (150 micrograms/kg) increased mean RL to 225% of baseline but bronchoconstriction produced by subsequent antigen challenge was completely prevented. Verapamil did not modify bronchoconstriction produced by aerosols of histamine and carbachol, agents that act upon airway smooth muscle. Further, it did not reverse the increase in RL induced by an intravenous infusion of carbachol. These results suggest that verapamil, at the dosage used, did not prevent allergic bronchoconstriction by a direct action on smooth muscle and therefore was effective by inhibiting the release of mast cell mediators.
 ...
PMID:Modification of allergic bronchoconstriction by a calcium antagonist: mode of action. 685 50

P-glycoprotein has been identified in mast cells stabilized in culture as well as in rat peritoneal mast cells, and is primarily concentrated on the granular membrane. This study aimed to define the role of this protein in the transport and accumulation of doxorubicin in mast cell granules and in its histamine releasing effect. The reverting agent verapamil, that is a substrate for P-glycoprotein, inhibited doxorubicin uptake in intact mast cells in a dose and time dependent manner, but had no effect on the exocytotic action of the antineoplastic drug. Doxorubicin was also concentrated in granules with intact membranes and the uptake was dependent on temperature and showed a trend for saturation. Verapamil and vinblastine, another substrate for P-glycoprotein, significantly reduced doxorubicin concentrations in intact granules. Similar results were obtained with the metabolic inhibitors sodium metavanadate, N-ethylmaleimide, and sodium azide, whereas ouabain, an inhibitor of sodium-potassium ATPase, was without effect. Doxorubicin was taken also up in granule remnants, consisting of a proteoglycan matrix without membrane, that are extruded from mast cells upon stimulation. However, the uptake was not dependent on temperature and was not modified by P-glycoprotein substrates or metabolic inhibitors. Rat peritoneal mast cells were examined for the expression of P-glycoprotein at the protein level with C219 monoclonal antibody, using Western blot, confirming that P-glycoprotein was expressed in mast cells. These data suggest the presence of a P-glycoprotein active in the transport of doxorubicin, in mast cell granules.
 ...
PMID:Transport of doxorubicin in mast cell granules and the effect of the calcium antagonist verapamil. 1036 60