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)

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

The effects of nifedipine and cimetidine on cold/restraint stress-induced gastric ulcers and glandular wall mast cell count were studied in rats. Two hours of restraint at 4 degrees C resulted in 90% ulceration rate in the glandular stomach with a decrease in glandular wall mast cell count in the mucosa, submucosa and muscle layer. Nifedipine in three doses (1, 5 and 10 mg/kg) administered i.p. 30 min before stress significantly and dose dependently prevented gastric ulceration and mast cell degranulation. Cimetidine, in doses of 50, 100 and 150 mg/kg, again administered 30 min before stress prevented only gastric ulceration dose dependently without a significant change in mast cell count. The results indicate that both nifedipine and cimetidine are equally effective to reduce gastric mucosal ulceration in response to stress. However, the unique effect of nifedipine to inhibit mast cell degranulation which was now clearly demonstrated may favour the potential value of this drug in the management of peptic ulcer disease in humans.
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PMID:Nifedipine versus cimetidine in prevention of stress-induced gastric ulcers in rats. 204 Mar 56

Histamine has been proved to be released during myocardial infarction and ischemic arrhythmias in dogs. The aim of the present experiments was to evaluate if ischemia and reperfusion modify histamine and lactate dehydrogenase (LDH) release in isolated guinea-pig heart. The results obtained show a steady increase of LDH release both in the ischemic and reperfusion phases. The release of histamine was reduced during the ischemic phase and increased significantly during reperfusion. A significant diminution of mast cell granule metachromasia was observed in the right auricles at the end of the reperfusion period. D-mannitol and reduced glutathione (GSH) modified the kinetics of histamine and LDH release. Cimetidine was able to decrease significantly the release of histamine during the ischemic and reperfusion phases and also reduced the release of LDH; triprolidine was completely ineffective. The results suggest that oxygen-derived free radicals may be involved in the pathogenesis of myocardial dysfunction after ischemia and reperfusion.
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PMID:Histamine and lactate dehydrogenase (LDH) release in ischemic myocardium of the guinea-pig. 244 Feb 79

The influence of the H1- and H2-histaminergic blockers promethazine and cimetidine, respectively, as well as of a combination of both drugs on the histamine release from rat ear skin, induced by compound 48/80, was studied. Cimetidine did not interfere with the effects of comp. 48/80, while promethazine increased almost three times the histamine-releasing effects of comp. 48/80. This effect of promethazine was reduced when the latter was combined with cimetidine. Cimetidine and promethazine did not produce any per se effect on the histamine content of the ear skin tissue. The two histaminergic blockers antagonized the vasodilation induced by exogenous histamine injected intradermally, the combination of the drugs in the higher dose used being most efficient. The effect of the combination was more pronounced as compared to that of promethazine when applied alone in the corresponding dose (25 mg/kg) and was almost equal to the effect of cimetidine administered alone in a dose of 200 mg/kg. The results suggest an important role for H2-histaminergic receptors in the skin vessels of rat as well as in the prevention of the mast cell degranulation at least in cases when it is induced by comp. 48/80.
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PMID:On the interaction between H1- and H2-histaminergic receptors in the histamine release and the realization of its vascular effects in rat skin. 246 94

Repeated intraperitoneal administration of compound 48/80 to rats produced gastric lesions, a decrease in connective tissue mast cells (CTMCs) and an increase in gastric mucosal mast cells (MMCs). The ratio of MMC to CTMC was significantly correlated with lesion formation. A mast cell stabilizer, MAR-99 (50 mg/kg), prevented lesion formation and changes in the mast cells. Omeprazole (20 or 60 mg/kg) significantly reduced the gastric lesions, but mast cell changes persisted. Cimetidine (50 mg/kg) could not inhibit compound 48/80-induced lesions nor a decrease in CTMCs, but did prevent an increase in MMCs. These facts suggest that in compound 48/80-induced gastric lesions chemical mediators released from CTMCs might be trigger factors, while intraluminal gastric acid might be an aggravating factor. Furthermore, the increase in MMCs might be regulated by histamine released from the CTMCs via H2 receptors and have no causal relation to lesions formation.
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PMID:Histological evaluation of mast cells in rat gastric mucosal lesions induced by compound 48/80. 280 59

The effects of somatostatin on ulcer formation, gastric acid secretion and histamine release were assessed during vagus nerve stimulation in rats. Direct electrical vagal stimulation significantly increased histamine release and acid output in gastric secretion but decreased mast cell counts in gastric glandular mucosa. Hemorrhagic ulceration on the gastric glandular mucosa was also observed. Somatostatin pretreatment (10 micrograms/kg) did not inhibit gastric ulcer formation, gastric acid secretion or histamine release induced by vagal stimulation. Cimetidine (an H2 blocker) pretreatment, however, significantly decreased gastric acid secretion as well as ulcer formation. The present study indicates the direct vagal stimulation increases gastric acid secretion and ulcer formation. These effects are partially histamine dependent. Somatostatin did not inhibit histamine release induced by vagal stimulation and reflects the inability of the drug to prevent ulcer formation and gastric output under these conditions in rats. However, the inhibition of basal gastric acid secretion produced by somatostatin might be useful clinically in humans.
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PMID:The lack of effects of somatostatin on gastric responses induced by electrical vagal stimulation. 614 Jun 85

The growth rate of Cloudman S91 melanoma cells was compared in groups of normal and immunologically compromised DBA/2 mice that had undergone thymectomy and treatment with antilymphocyte serum. Tumor growth was markedly accelerated in the immunosuppressed animals. Other groups of normal and immunosuppressed animals were treated with daily injections of either histamine, the H-2 antihistamine cimetidine, the H-1 antihistamine pyrilamine; or the mast cell stabilizer proxicromil. Histamine treatment accelerated tumor growth, but only in normal animals and had little effect on tumor growth in immunocompromised hosts. Cimetidine treatment tended to increase tumor growth in normal hosts but this was statistically significant in only 1 of 3 experiments. In contrast, treatment with cimetidine, pyrilamine, or proxicromil always resulted in significant retardation of tumor growth in immunosuppressed animals. These data are consistent with the notion that thymectomy and treatment with antilymphocyte serum results in enhanced tumor growth that is in part due to activation of histamine-dependent suppressor cells. In this system, histamine activation of suppressor cells may be reversed by treatment with either antihistamines or proxicromil, a drug that prevents mast cell release of histamine. However, since the effects of these drugs seem to depend on the immune status of the host, thorough evaluation of immunoregulatory function and careful testing to determine whether histamine blockers reduce or promote tumor growth would seem indicated when immunomodulatory treatment with these drugs is contemplated.
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PMID:The effect of histamine, antihistamines, and a mast cell stabilizer on the growth of cloudman melanoma cells in DBA/2 mice. 686 77

The effects of graded doses of cimetidine on both resting and reserpine-evoked gastric acid secretion were examined in relation to their influence on reserpine-induced ulceration, mast cell degranulation and mucosal microcirculatory changes in rat stomachs. Cimetidine 10 mg/kg or above reduced resting or reserpine-provoked gastric acid secretion as well as rumenal and glandular ulceration. However, non-acid-inhibiting doses, 5 mg/kg or below, continued to prevent glandular ulceration. Reserpine-evoked gastric glandular mucosal mast cell degranulation was unaffected by both acid-inhibiting and non-acid-inhibiting doses of cimetidine which dose-dependently blocked the superficial glandular mucosal microcirculatory volume changes. These results suggest that cimetidine prevents reserpine-induced glandular ulceration largely by blocking the ulcerogenic effect of histamine H2-receptor-mediated mucosal microcirculatory congestion, in contrast to antagonising rumenal lesions through acid inhibition; they also support the idea tha reserpine may release histamine mainly from the glandular mucosal mast cells. The possibility of another antiulcer mechanism, due to cytoprotection, is discussed.
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PMID:The influence of cimetidine, a histamine H2-receptor antagonist, on the gastric effects of reserpine in rats. 726 85

In the Hooded-Lister rat model, food protein induced intestinal anaphylaxis disrupts the migrating motor complex (MMC) and causes an increased frequency of migrating clusters of contractions (MCCs, including giant migrating contractions (GMCs)) and diarrhea. To determine whether mast cell mediators act on enteric neurons to initiate these alterations in motility, rats were sensitized by intraperitoneal injection of 10 micrograms egg albumin (antigen (Ag)). Seven days later two jejunal manometry catheters were implanted 2.5 cm apart. On day 14, motility was recorded in fasted rats before and after intraluminal challenge with 10 mg Ag in 0.5 mL saline, both without and after pretreatment by specific antagonists. Ag challenge of sensitized animals disrupted MMCs and caused an increase in total MCCs (including GMCs) and diarrhea. Atropine or hexamethonium abolished all intestinal motility, including Ag-induced MCCs, GMCs, and diarrhea. At higher doses, agents that inhibit mast cell degranulation, cromoglycate, doxantrazole, and quercetin, did inhibit Ag-induced MCCs, GMCs, and diarrhea, but at the expense of inhibiting normal intestinal motility. Cimetidine and diphenhydramine together inhibited normal cycling of the MMC, but did not abolish Ag-induced MCCs, GMCs, and diarrhea. Methysergide was ineffective, but cinanserin and WAY 100,289 significantly inhibited, and indomethacin most effectively blocked, the Ag-induced disruption of MMCs and the increase in MCCs, GMCs, and diarrhea. Thus, the altered motility and the diarrhea observed after food protein induced luminal challenge of sensitized rats is dependent upon myenteric neuronal circuitry. The mast cell stabilizers doxantrazole and quercetin block the response because of a nonspecific anticholinergic effect. Cinanserin and WAY 100,289 partially inhibit, and indomethacin most effectively blocks, the response, suggesting that activated mast cells release prostaglandins and perhaps 5-hydroxytryptamine, which stimulate the neuronal pathway.
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PMID:Mediation of altered motility in food protein induced intestinal anaphylaxis in Hooded-Lister rat. 877 13

The effects of adenosine receptor agonists on cytokine production in vivo were investigated in mouse models of endotoxemia. Selective adenosine A(3) (2-chloro-N(6)-(3-iodobenzyl) adenosine-5'-N-methyluronamide) (2-Cl-IB-MECA) and A(2A) (2-p-(2-carboxyethyl) phenethylamino-5'-N-ethylcarboxamido adenosine hydrochloride) (CGS 21860) receptor agonists were found to modulate endotoxin-induced cytokine responses in mice sensitized to D-galactosamine or primed with Corynebacterium parvum. The adenosine receptor agonists had similar effects in these models of endotoxemia, suppressing the production of tumor necrosis factor alpha (TNF-alpha) and interleukin-12 while enhancing that of interleukin-10. However, 2-Cl-IB-MECA also caused a dramatic increase in circulating histamine levels shortly after its injection into mice. The cytokine modulatory activities of 2-Cl-IB-MECA were mimicked by the mast cell depleting compound 48/80 and both drugs only produced such effects at doses that caused an elevation in circulating histamine levels. Furthermore, the capacity of 2-Cl-IB-MECA to modulate cytokine responses was greatly diminished when the drug was administered to mast cell deficient (WBB6F-W/W(V)) mice. Together, these results strongly suggest a role for histamine in cytokine modulation by 2-Cl-IB-MECA. Cimetidine, a histamine H(2) receptor antagonist, did not reverse cytokine modulation by 2-Cl-IB-MECA and pyrilamine, a histamine H(1) receptor antagonist, prevented the increase in serum histamine that was induced by 2-Cl-IB-MECA. This effect of pyrilamine and other histamine H(1) receptor antagonists confounded attempts to determine a role for the histamine H(1) receptor in cytokine modulation by 2-Cl-IB-MECA. However, under some experimental conditions, pyrilamine appeared to antagonize the modulatory effects of the adenosine A(3) receptor agonist on cytokine responses. The apparent antagonism of pyrilamine was unrelated to its suppressive effects on histamine release and appeared to reflect activity at the level of the histamine H(1) receptor.
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PMID:A role for histamine in cytokine modulation by the adenosine A(3) receptor agonist, 2-Cl-IB-MECA. 1246 Jun 44


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