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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the distribution and functional integrity of mast cells in intestinal longitudinal muscle in rats sensitized by two previous infections with Trichinella spiralis. A segment of jejunum was excluded from the gut before infection, and the remainder of the gut was anastomosed. Few mast cells were seen in muscle of noninfected control rats except in the region of the jejunal anastomosis. In rats sensitized by T. spiralis infection, mast cells were increased in number in the jejunum and the number of mast cells followed an aboral gradient down the entire length of the gut in continuity. In addition, mast cells were present in muscle of the excluded segment of sensitized rats. All mast cells were stained red with safranin. Functional integrity was assessed by the ability of mast cells to induce contraction after degranulation by antigen. In muscle from sensitized rats, contraction was induced in each region after exposure to T. spiralis antigen but not Nippostrongylus brasiliensis antigen. Contraction was inhibited by the mast cell stabilizer doxantrazole and the 5-hydroxytryptamine (5-HT) antagonist cyproheptadine. When antigen-induced contraction was expressed as a percentage of the maximum response of the tissue to exogenous 5-HT, the magnitude of contraction decreased along an aboral gradient down the intestine and correlated well (r2 = 0.878) with mast cell numbers. These results suggest that the increase in connective tissue mast cells in gut muscle after T. spiralis infection involves both local and systemic mechanisms.
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PMID:Distribution of mast cells in intestinal muscle of nematode-sensitized rats. 155 Feb 36

Mast cells secrete many biologically active compounds upon stimulation by immunoglobulin E (IgE) and specific antigen (Ag), anaphylatoxins, as well as a number of cationic compounds which include drugs, kinins and neuropeptides. The effects of the two naturally occurring polyamines, spermine (SP) and spermidine (SPD), on mast cell secretion were studied because they have been implicated in the modulation of cellular processes, possibly through their cationic charge or the regulation of calcium ions. SP and SPD over the range of 10(-7) to 10(-4) M inhibited the release of 5-hydroxytryptamine (5-HT, serotonin) triggered by compound 48/80 (C48/80) in a time- and concentration-dependent manner, as long as at least 2% calf serum (CS) was present. SP also inhibited secretion of both histamine and serotonin stimulated immunologically by using IgE and anti-rat IgE. This inhibition was not accompanied by cytotoxicity. The major available polyamine metabolites tested, N1-acetyl spermine (N1-acSP) and N8-acetyl spermidine (N8-acSPD), also showed inhibition in the presence of CS, whereas putrescine, N8,N1-hexamethylene-bis-acetamide (HMBA) and benzylamine did not. Fetal bovine serum (FBS), as well as human and rat serum, which do not contain polyamine oxidase, did not result in any inhibition with the polyamines tested. Inhibitors of the polyamine oxidase blocked the polyamine effect, indicating that the inhibition of mast cell secretion must derive from aldehydes produced from these polyamines. Addition of the aldehyde inhibitor phenylhydrazine (phi-HDZ), simultaneously with, but not following the polyamines, blocked their inhibitory effect, further strengthening the involvement of aldehydes. These results indicate that naturally occurring polyamines may regulate mast cell secretion through metabolic products of polyamine oxidase, a similar enzyme of which is also present in human liver, placenta and pregnant serum.
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PMID:Inhibition of mast cell secretion by oxidation products of natural polyamines. 159 9

SK&F 101926 is a synthetic octapeptide which was designed to promote free water excretion by antagonizing the action of antidiuretic hormone. The clinical and pathologic changes in rats resulting from lethal doses of SK&F 101926 have suggested that death is associated with respiratory failure and/or cardiovascular collapse. To define the relationships between respiratory failure, cardiovascular collapse, and death, respiratory and cardiovascular parameters were monitored in anesthetized rats following the intravenous administration of SK&F 101926 at a dosage (3 mg/kg) which resulted in 70% mortality. Within 5 min after receiving this dosage, mean arterial blood pressure was reduced to values between 30 and 40 mm Hg in all rats. This degree of hypotension was well tolerated by some rats and, consequently, was not considered to be the cause of death. Deaths occurred between 9 and 58 min after dosing and were preceded by respiratory depression involving marked reductions in respiratory rate and the lack of compensatory increases in tidal volume. At the time of respiratory arrest, heart rates remained above 200 beats/min, mean arterial blood pressure remained between 30 and 40 mm Hg, and there were no consistent changes in dynamic lung compliance or total pulmonary resistance. Pretreatment of rats with a mast cell stabilizing agent (disodium cromoglycate), a mast cell degranulating agent (compound 48/80), or a histamine/5-hydroxytryptamine blocking agent (cyproheptadine) prevented the reductions in respiratory rate and death caused by SK&F 101926. These pretreatments also reduced the effect of SK&F 101926 on blood pressure, but were not able to completely prevent the hypotension.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Respiratory and cardiovascular changes associated with toxic doses of a peptide antagonist of vasopressin in the rat. 160 Dec 32

1. Injection of lipopolysaccharide (LPS; 0.5-500 microgram kg-1) into mice induced a dose-dependent, slowly developing increase in hepatic content of 5-hydroxytryptamine (5-HT). This sustained increase could not be attributed to an LPS-induced alteration of the pharmacokinetic handling of 5-HT by stimulation of its uptake or inhibition of its degradation. 2. Regional differences were apparent in the tissue content of histamine and 5-HT between mast cell-deficient (W/Wv) and normal (+/+) mice. LPS administration (0.5 mg kg-1) gave comparable increases in the hepatic level of 5-HT in mast cell-deficient and normal mice. 3. Reserpine pretreatment (1 mg kg-1) selectively reduced 5-HT levels in the blood, spleen, liver, brain and lung of normal mice. Prior treatment with this agent also abolished the LPS (0.5 mg kg-1)-induced hepatic accumulation of 5-HT. 4. Accumulation of 5-HT in the liver by LPS (0.1 mg kg-1) was temporally associated with both a fall in the levels of circulating platelets, and a reduction in the concentration of 5-HT in the blood. The LPS dose-dependent (0.5-500 micrograms kg-1) increase in hepatic 5-HT content was associated with a similar dose-dependent reduction in the circulating levels of 5-HT. 5. Interleukin-1, alpha and beta (10 micrograms kg-1) and tumour necrosis factor alpha (TNF alpha) (1 mg kg-1) significantly enhanced the accumulation of 5-HT within the liver. Administration of TNF alpha (10 micrograms kg-1) potentiated the increase in hepatic 5-HT content seen with IL-1 beta (10 micrograms kg-1). 6. Electron microscopy revealed numerous platelets in the sinusoidal and perisinusoidal Disse spaces within the liver, in animals pretreated with LPS (0.1 mg kg '). The platelets retained their intact structure and showed no evidence of degranulation. 7. These data suggest that the LPS and cytokine-induced mobilization of 5-HT in the liver is associated with the hepatic translocation of platelets. This migration appears to be independent of platelet aggregation.
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PMID:The effect of lipopolysaccharide, interleukin-1 and tumour necrosis factor on the hepatic accumulation of 5-hydroxytryptamine and platelets in the mouse. 162 48

Substance P (SP) injected into the synovial cavity of the rat knee resulted in an inflammatory response as measured by plasma protein extravasation into the joint capsule. This response was dose dependent over the range of approximately 4 microM to approximately 200 microM. Part of this inflammatory response was mediated via mast cells as pre-treatment of the animals with a mast cell degranulator (compound 48/80) resulted in a 66% reduction of the response. A direct effect of SP on the vascular receptors may also contribute to the inflammatory response as pre-treatment with the substance P antagonist (SPA) D-Pro4 D-Trp7,9,10 SP4-11 also reduces the inflammatory response. Intra-articular injections of the H1 blocker diphenhydramine or the H2 blocker cimetidine significantly blocked the SP-induced inflammatory response. The 5-hydroxytryptamine (5-HT) antagonist methysergide proved to be even more potent in blocking the SP-induced inflammatory response. No synergistic inhibition was observed with combinations of the different antagonists. Intra-articular injections of 5-HT elicited a much more pronounced inflammatory response than that produced by a 10-fold higher concentration of histamine. The results suggest that SP produces increased vascular permeability partly via direct actions on the blood vessels and partly via mast cells. The inflammatory response occurring via mast cells appears to be mediated by histamine and to a greater extent by 5-HT.
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PMID:Mediators of substance P-induced inflammation in the rat knee joint. 170 85

The response to antigen (trinitro-phenyl-haptenized ovalbumin) and the modulatory role of several antiallergic drugs was studied in isolated hearts from actively sensitized rats. Antigen induced a triphasic effect on coronary flow (CF) and left ventricular pressure (LVP) characterized by short-term increase (0-1.5 min = phase 1) and a severe decrease (1.5-7.5 min = phase 2) followed by a less pronounced long-lasting decrease (7.5- greater than 20 min = phase 3). The first phase was accompanied with a substantial release of 5-hydroxytryptamine (5-HT), histamine, and leukotrienes measured in cardiac effluents. The histamine2 (H2)-receptor antagonist cimetidine (60 microM) reversed the antigen-induced increase in CF to a decrease. In contrast, H1-receptor blockade by mepyramine (6 microM) had no effect. Methysergide (10 microM) and ketotifen (0.1 microM) evoked a mild suppression during all three phases. Indomethacin (10 microM) was almost inactive while tolfenamic acid (1 microM) was slightly active in this respect during phase 2. Addition of the 5-lipoxygenase inhibitor AA 861 (1 microM) resulted in complete suppression of the antigen-induced decrease in CF. The leukotriene antagonist FPL 55712 (5 and 50 nM) evoked a dose-dependent suppression with respect to the anaphylactic phases 2 and 3. A similar reduction was obtained with sodium cromoglycate (1 mM). AA 861, FPL 55712, and sodium cromoglycate also suppressed the antigen-induced decrease in LVP. The antigen-induced histamine release was not affected by the aforementioned drugs. Our results provide evidence that H2-receptor blockade during cardiac anaphylaxis enhances coronary constriction and may be detrimental in this condition. On the other hand, leukotriene antagonists and 5-lipoxygenase inhibitors may exert beneficial effects during cardiac anaphylaxis. Further experiments in this area are needed to clarify the precise role of mast cell-generated mediators in cardiac anaphylaxis possibly leading to new therapeutic approaches in this life-threatening disorder.
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PMID:Characterization and modulation of antigen-induced effects in isolated rat heart. 172 33

The effects of two degranulators of mast cells and intestinal anaphylaxis on jejunal myoelectric activity were compared in rats fasted for 15 hours. Attempts to antagonize the motility changes were performed using antagonists of histamine and serotonin and a cyclooxygenase and lipoxygenase inhibitor. Hooded Lister rats were chronically fitted with electrodes implanted in the jejunal wall. A group of rats was sensitized to egg albumin and challenged 14 days later by intraduodenal infusion of antigen. Sensitized animals had serum titers greater than or equal to 1:64. The other group was administered with mast cells degranulators. Both 48/80 (1 mg/kg), a degranulator of connective mast cells, and bromolasalocid (2 mg/kg), acting on connective and mucosal mast cells, induced a phase of total spiking inhibition followed by a progressive irregular spiking activity until the recovery of migrating myoelectric complex pattern (about 3 hours after injection). In contrast, antigen challenge disrupted the migrating myoelectric complex pattern, which was replaced by a peculiar pattern characterized by propagated spike burst, lasting 98 +/- 11.3 minutes. Chlorpheniramine (1 mg/kg) antagonized only the inhibitory phase induced by degranulators and was ineffective on the intestinal anaphylaxis-induced motor changes. Methysergide (1 mg/kg) and indomethacin (5 mg/kg) significantly reduced the degranulator effects as well as the anaphylaxis-induced alterations of intestinal motility. It is concluded that anaphylaxis-induced motor disturbances are relevant to mucosal mast cell degranulation involving 5-hydroxytryptamine and arachidonic acid derivative products, whereas histamine release appears to be a minor component.
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PMID:Relationship between mast cell degranulation and jejunal myoelectric alterations in intestinal anaphylaxis in rats. 172 48

Contents of histamine, 5-hydroxytryptamine, functional state of heparinic proteoglycan have been studied in the rat peritoneal mast cells during various seasons of the year (January-February, May-June, July). In winter the mast cells have a high content of histamine and 5-hydroxytryptamine, heparinic proteoglycan of their granules is stained with both alcian blue and safranin. In summer (July) content of histamine in the mast cells is sharply decreased in comparison with that of 5-hydroxytryptamine and in May-June the content of both amines is decreased nearly to background values. Both during spring and summer periods heparinic proteoglycan of the mast cell granules is stained only with alcian blue and does not take safranin. A suggestion is made on independence of the seasonal changes of annual rhythmical pattern of histamine and 5-hydroxytryptamine contents in the mast cells. A conclusion is made concerning possible participation of the mast cell system of organs and tissues in the seasonal changes of biogenic amine levels in them.
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PMID:[Seasonal changes in the cytochemical properties of the peritoneal mast cells in rats]. 184 21

Peptides such as parathyroid hormone (PTH), somatostatin, and gastrin have been reported to stimulate mast cell mediator release. Preincubation of rat serosal mast cells with synthetic 1-34 bovine parathyroid hormone (1-34bPTH) significantly enhanced antigen-induced 5-hydroxytryptamine (5-HT) release. Enhancement of 5-HT release by 1-34bPTH was dose dependent between 5 and 2000 nM. In the absence of antigen, mean net 5-HT release was less than 1% when naive or passively sensitized mast cells were incubated with 1000 nM 1-34bPTH for time intervals up to 90 min. These findings indicate that 1-34bPTH, at relatively low concentration, potentiates antigen-induced 5-HT release from mast cells.
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PMID:Potentiation of antigen-induced mast cell activation by 1-34 bovine parathyroid hormone. 202 Jun 69

Fasted rats with chronically implanted electrodes were used for investigation of the effects of mast cell degranulation induced by compound 48/80 and BrX-537A and their antagonism by previous administration of 5-hydroxytryptamine (5-HT) antagonists on duodenal and jejunal myoelectric activity. Administered i.p., both 48/80 (1 mg/kg i.p.) and BrX-537A (2 mg/kg i.p.) abolished the intestinal spiking activity of duodeno-jejunum with a progressive recovery, BrX-537A being less active. These effects were dose-related. Injected prior to 48/80, methysergide (1 mg/kg) reduced by about 80% both duodenal and jejunal inhibition of spiking activity with early recovery of a normal pattern. In contrast, ketanserin (1 mg/kg) had selective reducing effects on the duration of the spiking inhibition induced by 48/80 and BrX-537A on the duodenum only. Zacopride (1 mg/kg) and ICS 205-930 (50 micrograms/kg) shortened and suppressed, respectively, the inhibition of intestinal spiking activity with early restoration of intestinal motility in both duodenum and jejunum. We conclude that, in fasted rats (i) the degranulation of peritoneal mast cells induces alterations in intestinal myoelectric activity through the release of 5-HT (ii) these effects are mainly mediated through both 5-HT1 and 5-HT3 receptors.
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PMID:Involvement of 5-hydroxytryptamine in the intestinal motor disturbances induced by mast cell degranulation in rats. 203 58


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