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

The turnover of neuronal histamine (HA) in nine brain regions and the spinal cord of the guinea pig and the mouse was estimated and the values obtained were compared with data previously obtained in rats. The size of the neuronal HA pool was determined from the decrease in HA content, as induced by (S)-alpha-fluoro-methylhistidine (alpha-FMH), a suicide inhibitor of histidine decarboxylase. The ratios of neuronal HA to the total differed with the brain region. Pargyline hydrochloride increased the tele-methylhistamine (t-MH) levels linearly up to 2 h after administration in both the guinea pig and the mouse whole brain. Regional differences in the turnover rate of neuronal HA, calculated from the pargyline-induced accumulation of t-MH, as well as in the size of the neuronal HA pool, were more marked in the mouse than in the guinea pig brain. The hypothalamus showed the highest rate in both species. There was a good correlation between the steady-state t-MH levels and the turnover rate in different brain regions. Neither the elevation of the t-MH levels by pargyline nor the reduction of HA by alpha-FMH was observed in the spinal cord, thereby suggesting that the HA present in this region is of mast cell origin. The half-life of neuronal HA in different brain regions was in the range of 13-38 min for the mouse and 24-37 min for the guinea pig, except for HA from the guinea pig hypothalamus, which had an extraordinarily long value of 87 min. These results suggest that there are species differences in the function of the brain histaminergic system.
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PMID:Histamine turnover in the brain of different mammalian species: implications for neuronal histamine half-life. 649 68

To determine the contribution by mast cells to the brain content of histamine (HA) and its metabolite tele-methylhistamine (t-MH), the number of mast cells, as well as the levels of HA and t-MH were measured in brain regions of mast cell-deficient (W/Wv) and control (+/+) mice. In agreement with earlier studies, mast cells were identified in control mouse brains, whereas W/Wv brains were devoid of mast cells. Contrary to earlier studies, no differences between these strains were found in the HA levels of any brain region, implying that mouse brain mast cells do not contribute significantly to brain HA levels. Brain t-MH levels were also not different between strains, except in hypothalamus, where W/Wv levels were higher; a significantly smaller W/Wv hypothalamus accounted for this difference. It is not certain that such differences are due to the absence of mast cells, since the W/Wv mutant is pleiomorphic, and the biochemical nature of this mutation remains uncertain. However, the absence of mast cells and presence of HA in the W/Wv mouse brain is direct evidence for the existence of non-mast cell HA in the brain. These results also show that mouse brain t-MH levels are predictive of non-mast cell HA in brain.
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PMID:Normal levels of histamine and tele-methylhistamine in mast cell-deficient mouse brain. 669

The concentration of plasma histamine may provide an index of mast cell activation (degranulation) and can be measured by a sensitive radioenzymatic assay based on its specific conversion to (3H)-methylhistamine in the presence of histamine-N-methyltransferase and (3H)-S-adenosyl-L-methionine. In this assay, the separation of excess (3H)-S-adenosyl-L-methionine from (3H)-methylhistamine requires several steps, for which a correction factors is necessary to maintain precision. In the present modification, duplicate 50-microliters aliquots of each plasma sample were incubated with histamine-N-methyltransferase and (3H)-S-adenosyl-L-methionine. A further aliquot, with an added standard of 200 ng/ml histamine, was incubated with histamine-N-methyl-transferase and (14C)-S-adenosyl-L-methionine. This standard was converted to (14C)-methylhistamine, and its recovery at the end of the assay corrected both for varying efficiency of methylation among plasma samples and for losses during the subsequent extraction and separation stages. The sensitivity of the assay was 25 pg/ml. The intra-assay and interassay coefficients of variation were 7.2% and 11.6%, respectively. In five asthmatics, antigen challenge caused a 28% fall in FEV1, and this was associated with a twofold to threefold rise in plasma histamine concentration. This assay may thus prove a useful method for assessing the role of mast cell release of mediators in vivo.
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PMID:A novel double-isotope technique for the enzymatic assay of plasma histamine: application to estimation of mast cell activation assessed by antigen challenge in asthmatics. 703 28

The whole brain content and subcellular distribution of histamine and its metabolite, tele-methylhistamine, were studied during postnatal development of the rat. Brain methylhistamine levels were similar to or greater than histamine levels, indicating that histamine methylation is a major metabolic pathway in neonatal brain, as it is in adults. When calculated per brain, histamine, methylhistamine, and histamine methyltransferase were all maximal 10 days after birth. In neonates, brain histamine was found almost entirely in nuclear fractions, whereas methylhistamine was found almost exclusively in supernatant fractions. By day 20, however, a greater proportion of both amines was localized in subcellular fractions containing synaptosomes, a finding consistent with histamine's suggested transmitter role. The ontogenic pattern of brain methylhistamine questions the mast cell origin of neonatal histamine, but may be consistent with a role for histamine in brain development.
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PMID:Ontogeny of subcellular distribution of rat brain tele-methylhistamine. 707 29

Multiple sclerosis (MS) lesions are associated with infiltration of T lymphocytes and macrophages that appear to mediate myelin destruction and gliosis (scarring). Mast cells are located perivascularly in the brain, are juxtaposed to neurons, and have been shown to secrete vasoactive and inflammatory mediators in response to neuropeptides and direct nerve stimulation. Mast cells have been previously identified in MS lesions, are activated by myelin basic protein, and can participate in the regulation of blood-brain barrier permeability, as well as in myelin destruction. Here, cerebrospinal fluid from MS patients and controls with other neurologic diseases was assayed for histamine, its major metabolite methylhistamine, and the specific mast cell marker tryptase. Histamine and methylhistamine were not elevated in MS. However, the mast cell specific proteolytic enzyme tryptase was significantly elevated in MS, suggesting that mast cell activation may be involved in the pathophysiology of this disease.
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PMID:Elevated mast cell tryptase in cerebrospinal fluid of multiple sclerosis patients. 781 59

Interstitial cystitis, a sterile bladder condition, is characterized by urinary frequency, urgency, burning and suprapubic pain. Increasing evidence indicates that interstitial cystitis is a heterogeneous syndrome that reflects an immune response to a variety of triggers. More than 50% of the patients have allergies, 30% have the irritable bowel syndrome and almost 20% suffer from migraine headaches. Increased numbers of mast cells have been reported in interstitial cystitis. Mast cell activation, which is critical if these cells were to be implicated in this syndrome, has been investigated by electron microscopy, which definitively shows mast cell secretion. Recently, methylhistamine, the major metabolite of histamine, and the specific mast cell marker, tryptase, were shown to be significantly elevated in urine of interstitial cystitis patients. Bladder biopsies from 53 patients were analyzed blindly for the number and degree of activation of mast cells using 4 different stains for light microscopy, as well as electron microscopy. Controls included 16 patients with incontinence and chronic bacterial cystitis. Mast cells in controls were less than 10/mm.2 and were all nearly intact. Surprisingly, mast cells from 11 cancer patients averaged 50/mm.2 but almost all were intact. In contrast, mast cells from 26 interstitial cystitis patients averaged 40/mm.2 and more than 90% were activated to various degrees. Therefore, bladder mast cell activation is a characteristic pathological finding in at least a subset of patients with interstitial cystitis.
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PMID:Activation of bladder mast cells in interstitial cystitis: a light and electron microscopic study. 786 1

1. Mast cell populations in rat lung and spleen were characterized by the presence of two specific protease markers, rat mast cell protease I and II, using both histochemical and radioimmunoassay techniques. Three mast cell populations with different size, morphology, and localization were found in lung and spleen and were identified according to the expression of rat mast cell protease I (RMCPI+) or rat mast cell protease II (RMCPII+) or of both proteases (RMCPI/II+). 2. All three mast cell types were in the vicinity of calcitonin-gene-related-peptide-immunoreactive (CGRP+) nerve fibres in controls as well as in rats infected by Nippostrongylus brasiliensis in which a large increase in the number of both RMCPII+ and RMCPI/II+ mast cells was found. Ablation of the CGRP+ fibres by neonatal treatment with capsaicin resulted in a marked increase in the number of RMCPII+ and RMCPI/II+ cells in lung and, even more, in spleen of adult rats. 3. The interaction of mast cells with CGRP+ C-fibres was assessed pharmacologically by evaluation of the effects of histamine H3-receptor ligands known to act on various types of nerve endings, including those of C-fibres. The effects of H3-receptor ligands were assessed in controls, nematode-infected rats and neonatally capsaicinized rats. Mast cell activity was evaluated by measurement of [3H]histamine synthesis from [3H]histidine. In control rats, administration of the H3-receptor agonist (R)-alpha-methylhistamine and antagonist thioperamide, decreased and enhanced respectively [3H]histamine synthesis in lung and spleen, indicating a tonic control of mast cell activity by histamine via H3-receptors. Such effects were not found in the jejunum, although RMCPII+ mast cells are in close apposition with neuropeptide-containing fibres. The effects of the H3-receptor agents were maintained in lung and spleen of nematode-infected rats, but were almost suppressed in capsaicinized rats. 4. It is concluded that the control of mast cells by histamine acting at H3-receptors involves neuropeptide-containing nerves and presumably reflects the operation of a local neuron-mast cell feedback loop controlling processes such as 'neurogenic inflammation'. This loop still functions when mast cells proliferate in an inflammatory condition. These observations suggest that the use of histamine H3-receptor agonists may constitute a novel therapeutic approach to limit excessive inflammatory responses resulting from dysregulation of this feedback loop.
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PMID:Functional relationship between mast cells and C-sensitive nerve fibres evidenced by histamine H3-receptor modulation in rat lung and spleen. 792 60

A survey is presented of neuromuscular drug involvement in 390 clinically severe anaphylactoid reactions (grades II-IV reported to a Sheffield laboratory from 1988 to the end of 1992 from hospitals throughout the UK. Despite advances in patient monitoring and newer drugs, the reporting frequency and individual drug involvement were remarkably similar to those of a previous report from the laboratory in 1988. The highly immunogenic drug suxamethonium still predominated (48% of reports), but there was now much reduced use of the similarly immunogenic drug, alcuronium. The incidence of reactions to vecuronium and atracurium remained similar (12% and 18% reports, respectively) and acceptable to the anaesthetist. However, in choosing drugs for individual patients, the anaesthetist may wish to note that vecuronium reactors mainly showed bronchospasm, and atracurium reactors hypotension. By a systematic laboratory investigation, based on measurement of plasma tryptase and urinary methylhistamine, reaction mechanisms were assessed in 53 reactions. Despite their overall clinical similarity, analysis revealed that only one reaction in three was likely to be due to IgE-mediated anaphylaxis (Type 1). Not only was suxamethonium the most frequently reported drug, but in this study 11 reactions were identified as Type 1 response: no allergic reactions were identified for either vecuronium or atracurium, although single cases were identified for alcuronium, gallamine, and tubocurarine, with two unidentified. The remaining reactions were judged to be non-immune, although most involved mast cell degranulation. These reactions were no less hazardous than Type 1 reactions (one death), and two deaths were recorded. The importance of laboratory investigation as a feature of postreaction care is emphasized.
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PMID:Adverse reaction to neuromuscular blockers: frequency, investigation, and epidemiology. 797 60

There is increased recognition that lung mast cell mediators not only produce the symptoms of acute asthma, but also result in the recruitment and activation of additional proinflammatory cells, such as eosinophils. Histamine, one of the major mast cell mediators, is known to have numerous effects on eosinophil function. These effects of histamine are mediated by distinct receptors on the surface of eosinophils, only some of which have been characterized. Prior studies have suggested that eosinophils have non-H1, non-H2 histamine receptors which mediate the chemotactic effects of histamine. We observed previously that the histamine-induced increase in cytosolic calcium in human eosinophils could not be blocked by classic H1 or H2 antagonists, but could be inhibited by the H3 antagonist thioperamide. The purpose of this study was to further characterize the pharmacologic properties of this calcium-linked histamine receptor. Using Fura-2 loaded eosinophils to measure the concentration of cytosolic calcium, we examined the effect of additional histamine receptor antagonists and agonists. We found that the pKb for the H3 antagonists thioperamide, impromidine, and burimamide (8.1, 7.6, and 7.2, respectively), were similar to those reported for H3 receptors in the central nervous system, suggesting that the eosinophil histamine receptor was similar to H3 receptors. However, when the known H3 agonists were tested for activity ([R]-alpha-methylhistamine, N alpha-methylhistamine), the potencies of these compounds were much less than the potency of histamine itself, indicating a significant difference between H3 receptors and this eosinophil histamine receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacologic characterization of a novel histamine receptor on human eosinophils. 800 6

Interstitial cystitis is a painful bladder disorder occurring mostly in women, and is presently diagnosed by clinical presentation, as well as the presence of mucosal glomerulations and inflammation on bladder distention. An increased number of bladder mast cells have been implicated in the pathophysiology of interstitial cystitis but previous reports of spot urine histamine have not confirmed bladder mast cell activation. The availability of easily measurable objective criteria could make the diagnosis easier. Histamine and its major metabolite, methylhistamine, were measured in spot and 24-hour urine specimens from a number of normal female volunteers, control patients and interstitial cystitis patients. In interstitial cystitis patients the histamine levels were only slightly increased in the spot (p < 0.01) and 24-hour urine (p < 0.03) collections. Methylhistamine, on the other hand, was greatly elevated in spot (p < 10(-10)) and 24-hour (p < 0.0008) urine samples. These results indicate that methylhistamine levels could serve as useful diagnostic end points for interstitial cystitis.
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PMID:Increased urine histamine and methylhistamine in interstitial cystitis. 775 67


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