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)

Recent studies have demonstrated a connection between xanthine oxidase-generated reactive oxygen intermediates and histamine release during ischemia-reperfusion. In the present work, the effect of modulation of the endogenous histamine level on the xanthine oxidase activity was examined during the reperfusion of a canine ileal segment following a 2 hr of complete ischemia. The xanthine oxidase activity and the plasma histamine level peaked simultaneously at the beginning of reperfusion, reaching mean values of 14.9 nmol/ml/min and 12.1 nmol/l, respectively. Pretreatment with aminoguanidine, a blocker of diamine oxidase (histaminase), resulted in significantly higher levels of histamine during reperfusion, but this elevation was not accompanied by a further increase in xanthine oxidase activity. Pretreatment with the mast cell stabilizer cromolyn significantly diminished the rise in plasma histamine level, with an unchanging activity of xanthine oxidase. No significant alteration could be observed in the postocclusive activity of xanthine oxidase following the intra-arterial administration of 0.5, 1, or 5 nmol of histamine during the last 10 min of the ischemic period. These data suggest that the amount of histamine liberated during reperfusion does not result in a further increase in the xanthine oxidase activity. The release of histamine is not a cause, but rather an effect of the elevated activity of intestinal xanthine oxidase.
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PMID:Studies on the relationship between xanthine oxidase and histamine release during intestinal ischemia-reperfusion. 138 3

Lodoxamide tromethamine, an orphan antiallergy drug, inhibits degranulation of mast cells that reside in the myocardium and inhibits xanthine oxidase located in myocytes and predominantly in the vascular endothelium. The hypothesis evaluated was that lodoxamide tromethamine would attenuate oxygen free radical damage. Isolated working rat hearts were perfused with Krebs-Henseleit buffer containing 0, 1, 10, 100, or 1,000 mumol/L lodoxamide tromethamine at 37 degrees and 24 degrees C with ischemic times of 22 and 93 minutes, respectively. These ischemic intervals yielded 50% survival and 50% return of function in untreated hearts. Lodoxamide treatment alone at the onset of reperfusion was also studied. Performance end points were aortic flow, pressure, and coronary flow. Biochemical analyses included serotonin collected from coronary effluent as a marker of mast cell degranulation, uric acid for xanthine oxidase inhibition, myocardial adenosine triphosphate, and carbonyl group concentrations. Performance data demonstrated that lodoxamide was beneficial in a log-linear dose response when given continuously at both temperatures. Percent of preischemic values for untreated and maximal responses at 1,000 mumol/L of lodoxamide were as follows: a mortality of 50% in nontreated hearts versus 0%; aortic flow, 47% to 94% (37 degrees C), 46% to 86% (24 degrees C); cardiac output, 60% to 98% (37 degrees C), 58% to 97% (24 degrees C); adenosine triphosphate, 59% to 90% (37 degrees C), 48% to 65% (24 degrees C). Serotonin was undetectable from any hearts. Uric acid concentrations and carbonyl group content did not change with increasing dose. Lodoxamide demonstrated no benefit when given only during reperfusion, suggesting injury occurred at times other than reperfusion.
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PMID:Prevention of ischemia-reperfusion injury by the allergy drug lodoxamide tromethamine. 192 38

It has been shown that plasma histamine significantly increases during myocardial infarction in the dog. Histamine is also released when the isolated guinea-pig heart is reperfused after 30 minutes of low flow perfusion. The release of histamine and lactate dehydrogenase (LDH) after left anterior descending coronary artery ligation and release were investigated in the present study and related to the changes in electrocardiographic parameters and to a computer-aided analysis of left ventricular mast cell metachromasia. Spontaneous release of histamine was unchanged during ischemia and increased after the release of the ligature, while we observed a steady increase of LDH overflow. In parallel, a significant diminution of mast cell granule metachromasia was observed in left ventricular samples. The perfusion of the heart with FeCl3/ADP (10 microM/100 microM), a free radical-generating system, significantly enhanced both the basal and ischemic-reperfusion release of histamine, while perfusion with N-t-butyl-phenyl-nitrone (BPN/100 microM) a "spin-trapper" molecule, significantly decreased histamine and LDH release and the loss in metachromasia of left ventricular mast cells induced by reperfusion. Inhibitors of xanthine oxidase (allopurinol, 10 microM) and of calcium-activated proteases (leupeptin, 10 microM) modified the kinetics of histamine and LDH release.
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PMID:Histamine release in acute coronary occlusion-reperfusion in isolated guinea-pig heart. 245 99

The pathogenesis of burn edema in the skin of rats appears to be related to a role for histamine, xanthine oxidase and oxygen radicals. Histamine and its metabolic derivatives increase the catalytic activity of xanthine oxidase (but not xanthine dehydrogenase) in rat plasma and in rat pulmonary artery endothelial cells. In thermally injured rats levels of plasma histamine and xanthine oxidase rise in parallel, in association with increases in uric acid. Burn edema is greatly attenuated by treatment of rats with the mast cell stabilizer, cromolyn, by complement depletion and by treatment with the H2 receptor antagonist, cimetidine, but is unaffected by neutrophil depletion. These studies suggest the following pathogenesis of burn edema: thermal trauma causes complement activation with anaphylatoxin release and mast cell secretion of histamine, leading to enhancement of xanthine oxidase activity and increased production of oxygen radicals which damage endothelial cells.
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PMID:Roles of histamine, complement and xanthine oxidase in thermal injury of skin. 257 May 31

Intravascular complement activation with either zymosan or cobra venom factor (CVF) impairs hepatic blood flow. Oxygen radical scavengers given at the time of complement activation attenuate the resulting hepatic ischemia. It is not clear whether complement-stimulated phagocytes or transiently ischemic then reperfused endothelial and parenchymal cells generated the toxic oxygen radicals. In this study, a group of rats were given allopurinol (50 mg/kg/day postoperatively X 3 days plus 100 mg/kg iv at t = 0), a specific inhibitor of xanthine oxidase, prior to complement activation with CVF (20 units/kg iv at t = 30 and 60 min) to determine whether xanthine oxidase-derived oxygen radicals contributed significantly to the hepatic perfusion abnormalities. Additional rats received lodoxamide tromethamine (10 mg/kg iv bolus at t = 0 followed by 20 mg/kg/hr iv infusion), a novel and potent inhibitor of mast cell release and inhibitor of xanthine oxidase, prior to the same CVF challenge to determine whether mast cell mediators were involved in the flow disturbance. Thermodilution cardiac output, mean arterial pressure, heart rate, hematocrit, and effective hepatic blood flow (EHBF) by galactose clearance were determined at t = 2 hr. The percentage change in total hemolytic complement activity (% delta CH50) was determined between serum obtained prior to sacrifice and at t = 0. Systemic hemodynamics and HCT were for the most part unaffected regardless of pretreatment group or challenge with CVF or saline. CVF challenge produced a 25% reduction (P less than 0.05) in EHBF in vehicle-pretreated rats compared to saline challenge. Neither allopurinol nor lodoxamide tromethamine significantly improved EHBF when given prior to CVF challenge.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Allopurinol and lodoxamide in complement-induced hepatic ischemia. 326 Jun 42

Chronic nicotine treatment worsens stomach mucosal damage by cold (4 degrees C) and restraint (stress): it dose- and time-dependently intensifies stress-evoked gastric glandular ulceration, mast cell degranulation and motility. Nicotine 50 micrograms/ml drinking water, given ad libitum to female Sprague-Dawley rats for 10 days, increases the sensitivity of the isolated stomach strip to acetylcholine-induced contractions; atropine abolishes this action. The isolated anococcygeus muscle from nicotine-treated male rats shows increased sensitivity to noradrenaline-induced contractions, but not to those by acetylcholine. Hexamethonium or atropine pretreatment antagonises stress-induced gastric effects in nicotine-drinking rats. Muscarinic M1- and M2-, but not M3-, receptor block (by pirenzepine, AF-DX 116BS and HHSiD, respectively) inhibits stress ulcer formation in female rats. Although tobacco smoking has been reported to increase free radical formation, mucosal xanthine oxidase which initiates free radical formation is uninfluenced by nicotine; antagonising this enzyme (by allopurinol) or hydroxyl free radical scavenging (by dimethylsulfoxide) does not lessen the effect of nicotine on stress-evoked ulceration. The findings suggest that chronic nicotine treatment produces partial ganglionic blockade of the vagal nerve which leads to muscarinic receptor supersensitivity. This phenomenon contributes significantly to the ulcer-worsening mechanism; muscarinic M1- and M2-receptors appear to be involved. The gastric ulcer-aggravating effect of nicotine in stressed rats appears not to be due to increased free radical formation.
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PMID:Nicotine and gastric ulcers in stress. 829 87

Recent work has demonstrated that inhibition of nitric oxide production with various nitric oxide synthesis inhibitors (L-NAME, L-NMMA) initiate leukocyte adhesion to postcapillary venules. The objective of this study was to elucidate the mechanism (or mechanisms) that promote the L-NAME-induced leukocyte response. Intravital microscopy was used to examine 25-40 microns venules in the rat mesentery. Nitric oxide synthesis was inhibited with L-NAME and leukocyte adhesion was observed over the first 60 min. The fourfold increase in leukocyte adhesion was independent of alterations in venular red blood cell velocity. The adhesion was superoxide-mediated inasmuch as superoxide dismutase (SOD) abolished the rise in leukocyte adhesion associated with nitric oxide synthesis inhibition. Ketotifen, a mast cell stabilizer, also abolished the rise in leukocyte adhesion induced by L-NAME. Histology revealed that mast cell degranulation occurred only in animals treated with L-NAME but not in animals pretreated with SOD or ketotifen. This observation suggests that mast cells become activated in the absence of nitric oxide production and superoxide contributes to the mast cell activation. The L-NAME-induced leukocyte adhesion could be reproduced by infusing hypoxanthine/xanthine oxidase (a superoxide generating system) or compound 48/80 (an activator of mast cells) and both responses were attenuated by ketotifen. These data suggest that inhibition of nitric oxide synthesis results in a superoxide and mast cell-dependent leukocyte adhesion.
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PMID:Nitric oxide synthesis inhibition induces leukocyte adhesion via superoxide and mast cells. 840 15

Previous reports indicate that intestinal intraluminal ethanol increases mucosal permeability (an index of mucosal injury) and histamine release by mast cells, and that the released histamine plays a role in mediating the increased permeability. In the present study, we investigated whether reactive oxygen metabolites and their major sources (xanthine oxidase and leukocytes) were involved in these ethanol effects. In rabbits, segments of the jejunum were perfused with a control solution or with 6% ethanol. In these segments, mucosal permeability was assessed by determining jejunal clearance of i.v. administered 51Cr-ethylenediaminetetraacetate (51Cr-EDTA) and 125I-bovine serum albumin (125I-BSA), and mast cell histamine release was estimated from the histamine concentration of the gut effluent. Ethanol increased 51Cr-EDTA clearance, 125I-BSA clearance, and histamine release. These ethanol effects decreased when the animals were given superoxide dismutase plus catalase (scavenger of O2- and H2O2, respectively), allopurinol, or oxypurinol (xanthine oxidase inhibitors). Administration of a monoclonal antibody (R15.7) against leukocyte adhesion molecule, CD18, inhibited completely the ethanol-induced increased 51Cr-EDTA and 125I-BSA clearances and histamine release. These and supplementary data suggest that (a) ethanol-induced mucosal injury and mast cell histamine release are mediated primarily by leukocytes, and (b) oxy radicals, especially those generated by xanthine oxidase, mediate these ethanol effects mainly by promoting leukocyte infiltration.
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PMID:Role of xanthine oxidase-derived oxidants and leukocytes in ethanol-induced jejunal mucosal injury. 901 59

Sprague-Dawley rats were restrained at 4 degrees C for 2 h (stress). Tungstic acid in a single dose of 0.01, 0.1, 1, 10, 100 or 300 mg/kg (dissolved in distilled water) was administered intragastrically to animals 30 min prior to stress. Stress induced significant gastric mucosal damage, whereas tungstic acid pretreatment dose-dependently reduced lesion formation. Doses of tungstic acid of 1 mg/kg and higher significantly (P < 0.05-0.001) decreased ulcers. The mucosal mast cell counts in rats pretreated with tungstic acid were significantly higher than those of control rats. In motility experiments using oral administration of amberlite pellets, pretreatment with tungstic acid dose-dependently reduced the gastric emptying rate during a 1 h period of stress. Gastric mucosal xanthine oxidase and superoxide dismutase (SOD) activities, after pretreatment with a single dose of tungstic acid, were not altered in stressed animals. It is suggested that tungstic acid effectively antagonizes stress-induced gastric ulcers, possibly by decreasing motility and mass cell degranulation. Xanthine oxidase and SOD activities and mucous content were not changed in the gastric mucosa by the present method of tungstic acid administration.
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PMID:Tungstic acid reduction of cold-resistant stress-induced ulceration in rats. 907 17

The relationship between the changes of active oxygen metabolism and blood flow and the formation, progression, and recovery of lesions was examined in the gastric mucosa of rats treated once with compound 48/80, a mast cell degranulator. Gastric mucosal lesions appeared 0.5 hr after compound 48/80 treatment, became worst at 3 hr, and recovered fairly well at 12 hr. Increases in gastric mucosal lipid peroxide content and xanthine oxidase and myeloperoxidase activities and decreases in gastric mucosal vitamin E and hexosamine contents and Se-dependent glutathione peroxidase activity occurred with the formation and progression of gastric mucosal lesions. These changes were attenuated with the recovery of the lesion. Gastric mucosal nonprotein SH content decreased with the formation of gastric mucosal lesions, and this decreased SH content returned to near the original level with lesion progression. No changes in gastric mucosal superoxide dismutase and catalase activities occurred with the formation, progression, and recovery of gastric mucosal lesions. Gastric mucosal blood flow decreased with the formation of gastric mucosal lesions, and this decreased blood flow recovered with lesion progression. Serum serotonin concentration, an index of mast cell degranulation, increased with the formation of gastric mucosal lesions, and this increased serotonin level was attenuated with lesion progression and recovery. Pretreatment with ketotifen, a connective tissue mast cell stabilizer, prevented the formation of gastric mucosal lesions, the increases of gastric mucosal lipid peroxide content, xanthine oxidase and myeloperoxidase activities, and serum serotonin level; and the decreases of gastric mucosal nonprotein SH content, glutathione peroxidase activity, and blood flow found at 0.5 hr after compound 48/80 treatment. These results indicate that the changes of gastric mucosal active oxygen metabolism and blood flow are closely related to the formation, progression, and recovery of gastric mucosal lesions in rats with a single compound 48/80 treatment. The present results also suggest that this compound 48/80-induced gastric mucosal injury could be a kind of ischemia-reperfusion-induced injury occurring through degranulation of connective tissue mast cells.
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PMID:Relationship between changes of active oxygen metabolism and blood flow and formation, progression, and recovery of lesions is gastric mucosa of rats with a single treatment of compound 48/80, a mast cell degranulator. 920 Oct 88


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