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)

Biochemical mechanisms of desensitization were explored by using peritoneal mouse mast cells saturated with monoclonal mouse IgE anti-DNP antibody. It was found that a 1-min incubation of the sensitized cells with 0.01 micrograms/ml DNP-HSA in the absence of Ca2+ was sufficient to desensitize the cells completely. The treated cells failed to release a detectable amount of histamine upon incubation with an optimal concentration (0.1 to 1.0 micrograms/ml) of DNP-HSA and Ca2+. Determination of the number of antigen molecules bound to mast cells revealed that only a small (less than 10%) fraction of cell-bound IgE antibody molecules reacted with desensitizing antigen, and that desensitized cells and untreated (sensitized) cells could bind comparable amounts of antigen upon incubation with rechallenging antigen. However, the binding of antigen molecules to desensitized cells failed to induce any of the early biochemical events, i.e., phospholipid methylation, cAMP rise, and 45Ca uptake, as well as histamine release. It was also found that intracellular cAMP levels in desensitized cells were comparable to those in sensitized cells. Desensitization by a suboptimal concentration of DNP-HSA was prevented by inhibitors of methyltransferases, such as 3-deaza adenosine plus L-homocysteine thiolactone. Sensitized cells pretreated with 0.01 micrograms/ml DNP-HSA in the absence of Ca2+ and in the presence of the methyltransferase inhibitors responded to an optimal concentration of antigen for histamine release when they were rechallenged in the presence of Ca2+. Inhibition of desensitization by methyltransferase inhibitors was reversed by the addition of S-adenosyl-L-methionine to the system. The results indicated that the activation of methyltransferases, induced by receptor bridging, is involved in the process of desensitization. Desensitization was inhibited by reversible inhibitors of serine proteases, such as p-aminobenzamidine, indole, and synthesized substrates of rat mast cell proteases. It was also found that diisopropylfluorophosphate (DFP), an irreversible inhibitor of serine proteases, completely blocked desensitization at the concentration of 10 to 40 nM. This concentration of DFP did not affect the antigen-induced histamine release, whereas 100- to 1000-fold higher concentrations of DFP did inhibit histamine release. The results suggest that serine proteases are involved in both the induction of histamine release and desensitization, and that the protease involved in desensitization is distinct from that involved in triggering histamine release.
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PMID:Biochemical analysis of desensitization of mouse mast cells. 258 46

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 synthesis and degradation of histamine by dog fundic mucosa was studied by using cells dispersed by enzymatic digestion and separated sequentially by velocity sedimentation in an elutriator rotor, and by density gradient. Histidine decarboxylase activity was found in appreciable amounts in fractions highly enriched in mast cells when these cells were studied intact, whereas only trace activity was detected in homogenates of these mucosal mast cells or of whole mucosa. Unlike the rat gastric mucosal histamine cell, dihydroxyphenylalanine decarboxylase activity was not present in the canine fundic mast cell. Serotonin, which is found in the rat peritoneal mast cell, was not detectable in the canine mast cell. The histamine-degrading enzyme, histamine methyltransferase, was also present in gastric mucosal cells, but not diamine oxidase. This methyltransferase activity was primarily associated with parietal cells and was not found in the mast cell-enriched functions. For comparison, fractions containing 60%-80% mast cells were enriched by elutriation from enzyme-dispersed cells of canine liver. As with the gastric mast cells, histidine decarboxylase activity was found in intact cell, but it was lost upon cell disruption.
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PMID:Histamine synthesis by intact mast cells from canine fundic mucosa and liver. 705 26

The inhibitory effect of cromakalim on the mediator release from mast cells caused by antigenantibody reactions was in controversy with the specific antigen used. However, it has recently been observed that cromakalim inhibits the release of mediators from superfused tracheal and parenchymal strips or lung mast cells after passive sensitization with the IgG1 antibody. An attempt, therefore, was made to determine the inhibitory mechanisms of cromakalim on the release of mediators such as histamine and leukotriene released by the activation of enzymes during mast cell activation. Guinea pig lung mast cells were purified through enzyme digestion, rough percoll and continuous percoll density gradients. The purified mast cells were prelabeled with [3H]palmitic acid. PLD activity was assessed more directly by the production of labeled phosphatidylethanol by PLD-mediated transphosphatidylation in the presence of ethanol. In the cells labelled with [3H]myristic acid, [3H] DAG production was measured. The methyltransferase activity was assessed by measuring the incorporation of [3H]methyl moiety into phospholipids in sensitized mast cells labelled with L-[3H] methylmethionine. cAMP level was measured by radioimmunoassay. Cromakalim resulted in a decrease in the amount of histamine and leukotrienes releases by 30% in the ovalumin-induced mast cell. Cromakalim had little effect on phospholipase D activity enhanced by the activated mast cell. Cromakalim inhibited the initial increase of diacylglycerol production during mast cell activations. Cromakalim inhibited the phospholipid methylation increased in the activated mast cell. These results show that cromakalim decreases histamine release by inhibiting the initial increase of 1,2-diacylglycerol during the mast cell activation, which is mediated via the phosphatidylinositide-phospholipase C system rather than the phosphatidylcholine-phospholipase D system. Furthermore, cromakalim reduces phosphatidylcholine production by inhibiting the methyltransferase, which decreases the conversion of phosphatidylcholine into arachidonic acid and inhibits the production of leukotrienes.
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PMID:The effects of cromakalim on the mediator releases from guinea pig lung mast cell activated by specific antigen-antibody reactions. 899 65

The chick pineal gland contains histamine and tele-methylhistamine. The levels of both substances are elevated after treatment of chicks with the amino acid precursor of histamine, L-histidine (1 g/kg, ip). In control and L-histidine-loaded animals the pineal levels of histamine and tele-methylhistamine are higher in light-exposed than in dark-adapted animals (measured at the end of the light phase and in the middle of the dark phase of 12 hr light, 12 hr dark illumination cycle, respectively). The chick pineal gland contains histamine-immunofluorescent cells displaying mast cell morphology; they are seen in the vicinity of the capsule and in the parenchyma. Enzymatic studies showed the presence of the activity of histamine synthesizing and inactivating enzyme, i.e., L-histidine decarboxylase (HDC) and histamine-methyltransferase (HMT). The detected enzyme activities were sensitive to specific inhibitors of HDC (alpha-fluoromethylhistidine and alpha-hydrazinohistidine) and HMT (quinacrine and metoprine); inhibitors of aromatic amino acid decarboxylase alpha-methyl-DOPA and NSD-1015 were inactive on HDC. Exogenous histamine added to organ-cultured chick pineals strongly stimulated endogenous cyclic AMP accumulation and moderately increased melatonin secretion. The data, considered collectively, suggest that in avians histamine, probably originating from the pineal mast cell compartment, may function as a regulator of pineal gland activity.
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PMID:Histamine in the chick pineal gland: origin, metabolism, and effects on the pineal function. 906 67

It is likely that mast cell and histamine metabolism are involved in autoimmune tissue injury such as cutaneous lupus erythematosus (LE) because different histamine receptors can regulate Th1 and Th2 cells. In order to verify the role of the axis of mast cell-histamine metabolism-histamine receptor, the autoimmune mouse has been investigated. The MRL/Mp-lpr/lpr (MRL/lpr) mouse is a good model for the spontaneous development of skin lesions similar to those seen in human LE. In skin lesions from MRL/l mice, there are many infiltrating T cells and mast cells in the dermis and impaired histamine metabolism, in which the low activity of histamine-N-methyltransferase and the related prolonged effects of histamine in the skin tissue seem to play a definite pathological role in the development of spontaneous lupus-like eruptions. The expression of H2R on the mast cell decreases within these skin lesions at 5 months of age. It is interesting that the activity of HMT runs in parallel with the expression of H2R over the time course of the skin changes in MRL/l mice, but the relationship between these two observations remains obscure. The accumulation of mast cells expressing H2R and prolonged effects of histamine may occur to regulate the production of Th1 and Th2 cytokines in the skin lesions of MRL/l mice.
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PMID:Mast cells and histamine metabolism in skin lesions from MRL/MP-lpr/lpr mice. 1916 42