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)

Systemic administration of capsaicin aggravates ethanol-induced injury of rat gastric mucosa. We evaluated the effect of subcutaneous administration of capsaicin on the gastric mucosa and on inflammatory mediators in saline- and ethanol-treated rats. Functional ablation of primary afferent C-fibers by capsaicin (total 100 mg/kg subcutaneous) tripled ethanol-induced damage. Pretreatment with ketotifen, a mast cell stabilizer (1 mg/kg) protected rat gastric mucosa from the amplified injury induced by capsaicin and ethanol. Tempol, a selective nontoxic cell-permeable nitroxide, completely prevented the amplified gastric ulceration induced by capsaicin and ethanol. This was accompanied by a significant decrease in leukotriene B4 and C4 generation. It is therefore suggested that mast cells and free radicals contribute to the amplified injury observed in rats pretreated with capsaicin and ethanol and that the pharmacological modulation of mast cell release and scavenging of free radicals may be of therapeutic efficacy in the prevention of gastric injury.
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PMID:Ketotifen and nitroxides decrease capsaicin-augmented ethanol-induced gastric damage in rats. 772 77

We compared the protective effect of DS-4574, a peptidoleukotriene receptor antagonist with mast cell stabilizing action, on rat gastric mucosal injury induced by acidified ethanol to that of LY171883, a selective peptidoleukotriene receptor antagonist. Oral treatment with DS-4574 (1-10 mg/kg) or LY171883 (100 and 300 mg/kg) markedly suppressed this mucosal necrosis. Moreover, DS-4574 (10 mg/kg) significantly inhibited both mucosal edema and degranulation of mucosal mast cells. LY171883 (300 mg/kg) protected only from mucosal edema, but not degranulation of mucosal mast cells. These results suggest that DS-4574 possesses protective actions against gastric injury including the reduction of degranulation of mucosal mast cells, which are different from those of LY171883.
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PMID:Protective effect of DS-4574 on gastric mucosal injury induced by acidified ethanol in rats. 790 21

Alcohol-induced hypersecretion probably contributes to chronic alcoholic pancreatitis. Feeding of raw soybean flour or soybean trypsin inhibitor also stimulates protein secretion of the pancreas. Therefore, we tested whether or not the pancreatic damage is increased by additional feeding of raw soybean flour in rats fed 20% ethanol. After 11 months, we classified the morphological lesions of the pancreas into seven stages of severity calculated by means of a discriminating procedure. In order to characterize the secretory capacity of the pancreas, we measured the outputs of lipase, phospholipase, A, alpha-amylase, carboxypeptidase A, chymotrypsin, and bicarbonate. Compared with the alcohol-fed animals, the rats fed with alcohol and soya exhibited a lower average degree of morphological damage in the pancreas. Hypertrophy and hyperplasia of the parenchyma and accumulation of secretory products within the acinar cells were main features. On the other hand, some separate regions of the pancreas showed intraductal secretion precipitates as well as plugs, which were sometimes associated with atrophy of acinar cells. Feeding with soybean diet grossly reduced the alcohol-induced enzyme hypersecretion. In the early phase of alcohol-induced pancreatic damage, long-term soybean flour diet thus reduces morphological lesions and hypersecretion of the rat pancreas, whereas protein synthesis in the acinar cells appears increased. However, the precipitation of secretory products on ductal epithelium, the increased formation of plugs, and the more frequent acinar atrophies suggest the development of significant tissue injuries.
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PMID:[Modification of alcohol-induced pancreatic damage in rats by soybean diet]. 816 30

Several lines of evidence suggest a role for mast cells as modulators of gastric mucosal integrity, but the effect of antigenic mast cell activation on mucosal resistance to injury has not previously been examined. In this study, rats were sensitized to the nematode Nippostrongylus brasiliensis and were studied 35-42 days later. With use of an ex vivo gastric chamber preparation, the stomach was exposed for 10 min to 20% ethanol. In some rats, antigen was administered intra-arterially 10 min before application of ethanol. Sensitized rats exhibited similar levels of ethanol-induced gastric injury as control rats, despite having significantly greater numbers of mucosal mast cells. However, antigen administration, which did not in itself produce mucosal injury, significantly augmented (approximately 3-fold) the extent of injury in sensitized but not control rats. Prior treatment with dexamethasone depleted mucosal mast cells in control and sensitized rats. Moreover, this treatment abolished the increase in mucosal injury observed in sensitized rats treated with antigen and topical ethanol. Pretreatment with a leukotriene D4-receptor antagonist, but not a platelet-activating factor-receptor antagonist or a cyclooxygenase inhibitor, abolished the increased susceptibility of sensitized rats to gastric damage induced by antigen and topical ethanol. These results suggest that mucosal mast cell number per se does not influence mucosal susceptibility to injury; however, activation of mast cells markedly increases the susceptibility to injury through a peptidoleukotriene-dependent mechanism.
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PMID:Mast cell activation augments gastric mucosal injury through a leukotriene-dependent mechanism. 820 31

The antiulcer effect of aqueous extracts of the leaves of the neem tree was investigated in rats exposed to 2-h cold-restraint stress or given ethanol orally for 1 h. Extracts were administered in doses of 10, 40, or 160 mg leaf/kg body weight, either as single- or five-dose pretreatment regimens. Neem dose-dependently reduced gastric ulcer severity in rats subjected to stress and also decreased ethanol provoked gastric mucosal damage. The extract appeared to prevent mast cell degranulation and to increase the amount of adherent gastric mucus in stressed animals. These effects may explain, at least in part, the mode of the antiulcer action of neem.
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PMID:The gastric antiulcer effects of the leaves of the neem tree. 831 89

Postoperative adhesions are a major cause of bowel obstruction and infertility. Since mast cells in the intestinal wall have been shown to degranulate after bowel manipulation, we investigated a possible role for these cells in peritoneal adhesion formation. Adhesions were created in weanling rats using cecal scraping and the application of 95% ethanol. The rats were treated with saline or one of two mast cell stabilizers, disodium cromoglycate (DSCG) or nedocromil sodium (NED), intraperitoneally 30 minutes before laparotomy and at the time of abdominal closure. The adhesions were assessed blindly 1 week later using a standardized scale. When the results in rats treated with DSCG were compared with those in rats treated with saline, the DSCG rats had significant attenuation of adhesion formation at 2 mg/kg (1.05 +/- 1.0 versus 2.15 +/- 0.8) and 10 mg/kg (1.2 +/- 0.9 versus 2.71 +/- 0.5). The application of NED decreased adhesions at a dose of 100 mg/kg (1.33 +/- 1.2 versus 2.4 +/- 0.8) but not at 10 mg/kg (2.4 +/- 0.8 versus 2.4 +/- 0.8). Histologic analysis using toluidine blue staining was done to assess the effect of DSCG on mast cell degranulation in the same adhesion model. DSCG significantly decreased the number of degranulated mast cells in the bowel wall when compared with saline (7.16 +/- 0.6 mast cells/high-power field [hpf] versus 12.4 +/- 1.9 mast cells/hpf). These data suggest that mast cells play an important role in the initial stages of peritoneal adhesion formation. In the future, pharmacologic inhibition of mast cell degranulation may be a useful adjunct for the prevention of postoperative adhesions.
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PMID:Role of mast cells in peritoneal adhesion formation. 838 Mar 13

Anti-inflammatory properties have been ascribed to a series of N-(fluorenyl-9-methoxycarbonyl) amino acids called leumedins that inhibit the activity of granulocytes and T-lymphocytes. We evaluated one of these leumedins, N-(fluorenyl-9-methoxycarbonyl) leucine (NPC 15199), in a model of ileitis in guinea pigs. Ileitis was induced by intraluminal trinitrobenzenesulfonic acid (TNBS 30 mg/kg in 50% ethanol) in anesthetized guinea pigs. NPC 15199 was administered daily (10 or 100 mg/kg, s.c.). After 7 days, the guinea pigs were anesthetized, and saline was administered intraluminally into an ileal loop created at the site of TNBS administration and was withdrawn after 30 min. The changes in lavage protein, nitrite levels, myeloperoxidase (MPO) activity and mast cell numbers were used as indices of inflammation and injury. NPC 15199 (10 or 100 mg/kg) attenuated or abolished TNBS-induced elevations in lavage protein and nitrite content. Only the high dose of NPC 15199 (100 mg/kg) attenuated ileal MPO activity and mast cell hyperplasia. Histological disturbances induced by TNBS administration included crypt hypertrophy, mucosal and submucosal fibrosis and smooth-muscle hyperplasia. These disturbances were reversed by high-dose NPC 15199 (100 mg/kg) but were minimally affected by low-dose NPC 15199 (10 mg/kg). We conclude that NPC 15199 prevents mucosal injury and dysfunction in this model of intestinal inflammation. Inhibition of granulocyte infiltration does not appear to be essential for the beneficial effects of NPC 15199 and suggests that the alternative actions of NPC 15199 may be pertinent to this model.
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PMID:Guinea pig ileitis is attenuated by the leumedin N-(fluorenyl-9- methoxycarbonyl)-leucine (NPC 15199). 839 62

To enhance the already high quality of diffraction data for crystals of the hydrophobic protein crambin, X-ray data were collected at 130 K by the method of H. Hope to 0.83 A resolution. Refinement with PROLSQ yields a model with an R value of 10.5%. The final model had three parameter anisotropic vibration factors for all atoms, which included 367 protein heavy atoms, 372 hydrogen atoms and 144 solvent atoms with one ethanol molecule. Dihedral angles and hydrogen-bonding distances generally agree with earlier studies of high-resolution protein structures, but some new patterns are noted. Solvent-related helix distortions are reminiscent of those described by others. Helix and beta-sheet regions show distinct patterns in their side-chain conformations. Despite crambin's hydrophobic nature, its accessible surface area in the crystal is surprisingly close to that of water-soluble proteins like myoglobin and carboxypeptidase A. More of crambin's hydrophobic surface is buried in the crystal, perhaps accounting for its high order of diffraction. A total of 24% of the 46 residues show discrete disorder at 130 K. This includes five side-chains at both 300 and 130 K, and six more side-chains and an ethanol molecule at 130 K. Disorder is associated with the sequence microheterogeneity at Pro/Ser22 and Leu/Ile25, with space filling or with solvent disorder. Correlated conformations extend over three to five residues. The patterns of disorder in this structure reveal important principles of protein structure and its dynamics. Finding disordered groups correlated over 5 to 8 A suggests that co-ordinated motion extends in groups rather than simply as uncorrelated movement around an atom center. Thermal diffuse scattering experiments on insulin and lysozyme are consistent with this interpretation. Nearly all of the protein-bound solvent has been located. Less than 1% of protein accessible surface area remains uncovered by solvent or crystal contacts. Preliminary analysis of the solvent network reveals two main networks in each of four solvent regions.
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PMID:Atomic resolution (0.83 A) crystal structure of the hydrophobic protein crambin at 130 K. 845 May 43

Gastric actions of Nw-nitro-1-arginine methyl ester (L-NAME) were investigated in rats, as this agent is a reliable nitric oxide synthase inhibitor L-NAME solutions were placed in subcutaneous osmotic minipumps which continuously released L-NAME at 0.1, 1.0, 10, or 40 mg/kg/day. L-NAME dose and time-dependently enhanced stress-induced gastric ulceration but did not affect mucosal mast cell population. Ulcerogenic actions of L-NAME were reversed by L-arginine but not by D-arginine. Ten L-NAME treatment also enhanced the ethanol-induced gastric mucosal damage, depressed gastric mucosal blood flow but did not alter gastric mucus, secretory volume, or acid output. It is concluded that in the present models, chronic nitric oxide synthase inhibition enhanced ulcerogenesis by decreasing mucosal resistance due to reduced mucosal blood perfusion. This implicates nitric oxide as a mucosal defense factor which acts in part by maintaining mucosal blood flow.
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PMID:Effects of chronic nitric oxide synthase inhibition in cold-restraint and ethanol-induced gastric mucosal damage in rats. 862 50

The adenosine analog, N-ethylcarboxamidoadenosine (NECA), causes transient activation of phospholipase C and an enhancement of antigen-induced secretion in a rat mast cell (RBL-2H3) line via adenosine A3-receptors (Ramkumar et al., J. Biol. Chem. 268:16887, 1993) by a mechanism that is inhibited by bacterial toxins and potentiated by dexamethasone (Ali et al., J. Biol. Chem. 265:745-753, 1990). Here we show that NECA synergizes the secretory response to Ca(2+)-ionophore as well as to antigen. The ability of NECA to synergize the secretory responses persisted for 10 to 20 min, long after the early phospholipase C-mediated reactions to NECA had subsided. NECA caused, however, a dose-dependent sustained activation of phospholipase D, as indicated by the formation of [3H]phosphatidic acid, or in the presence of 0.3% ethanol, [3H]phosphatidylethanol. This activation was associated with a sustained increase in diglycerides, in protein kinase C activity and in the phosphorylation of myosin light chains by protein kinase C. The generation of diglycerides was enhanced in dexamethasone-treated cells and suppressed in cells that had been treated with cholera toxin or pertussis toxin. Collectively, the studies suggested that the generation of diglycerides via phospholipase D and the associated activation of protein kinase C were, by themselves, insufficient signals for secretion in RBL-2H3 cells, but that these reactions synergized responses to stimulants such as antigen or A23187 that caused substantial increases in [Ca2+]i.
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PMID:Sustained activation of phospholipase D via adenosine A3 receptors is associated with enhancement of antigen- and Ca(2+)-ionophore-induced secretion in a rat mast cell line. 863 57


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