Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Histamine is implicated in the regulation of brain functions through three distinct receptors. Endogenous histamine in the brain is derived from mast cells and neurons, but the importance of these two pools during early postnatal development is still unknown. The expression of histamine H1-receptor in the rat brain was examined using in situ hybridization during postnatal development and in adults. For comparison, the expression of L-histidine decarboxylase (HDC) in the two pools was revealed. H1-receptor was evenly expressed throughout the brain on the first postnatal days, but resembled the adult, uneven pattern already on postnatal day 5 (P5). HDC was expressed in both mast cells and tuberomammillary neurons from birth until P5, after which the mast cell expression was no more detectable. In adult rat brain, high or moderate levels of H1-receptor expression were found in the hippocampus, zona incerta, medial amygdaloid nucleus and reticular thalamic nucleus. In most areas of the adult brain the expression of H1-receptor mRNA correlates well with binding data and histaminergic innervation. A notable exception is the hypothalamus, with high fibre density but moderate or low H1-receptor expression. Systemic kainic acid administration induced increased expression of H1-receptor mRNA in the caudate-putamen and dentate gyrus, whereas no change was seen in the hippocampal subfields CA1-CA3 or in the entorhinal cortex 6 h after kainic acid injections. This significant increase supports the concept that histaminergic transmission, through H1-receptor, is involved in the regulation of seizure activity in the brain.
 ...
PMID:Postnatal expression of H1-receptor mRNA in the rat brain: correlation to L-histidine decarboxylase expression and local upregulation in limbic seizures. 974 57

TGF-beta1 is a member of a family of polypeptide factors that control proliferation, differentiation, chemotaxis, and other functions in many cell types. TGF-beta1 has been shown to inhibit many immunologic functions. However, here we report that TGF-beta1 has an important role in the elicitation of IgE-dependent allergic reactions. The synthetic antisense TGF-beta1 oligonucleotides dose-dependently inhibit passive cutaneous anaphylaxis (PCA) reaction and histamine release from the mast cells activated by anti-DNP IgE in rats. The level of cAMP in mast cells, when antisense TGF-beta1 oligonucleotides was added, significantly increased approximately 7-fold compared with that of basal cells. The antisense TGF-beta1 oligonucleotides also had a significant inhibitory effect on anti-DNP IgE-induced TNF-alpha release from mast cells. In situ hybridization analysis showed that the PCA reaction sites treated with antisense TGF-beta1 oligonucleotides exhibited no detectable levels of TGF-beta1 and L-histidine decarboxylase mRNA after anti-DNP IgE stimulation, whereas the PCA reaction sites treated with sense TGF-beta1 oligonucleotides possessed significant amounts of their mRNA. Additionally, neutralizing Ab to TGF-beta1 blocked the PCA reaction significantly, but its Ab did not inhibit peritoneal mast cell-released histamine upon treatment with anti-DNP IgE. Our results suggest that TGF-beta1 is critical to the development of IgE-dependent anaphylaxis reactions.
 ...
PMID:Role of TGF-beta 1 on the IgE-dependent anaphylaxis reaction. 1020 43

Sodium salicylate (NaSal) is a commonly used agent with a wide pharmacological spectrum. The objective of the present study was to investigate the effect of NaSal on anaphylaxis. NaSal (10-1 and 1 mm) significantly inhibited systemic anaphylaxis induced by compound 48/80 in rats. NaSal also significantly inhibited local anaphylaxis activated by anti-dinitrophenyl (DNP) immunoglobulin E (IgE). NaSal (10-1 and 1 mm) significantly inhibited histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. Northern-blot analysis demonstrated that a significantly reduced level of the mRNA of L-histidine decarboxylase was expressed in mast cells treated with NaSal, compared with that without NaSal. NaSal (10-2 and 10-1 mm) had a significant inhibitory effect on anti-DNP IgE-induced tumour necrosis factor-alpha secretion from RPMC. The level of cyclic AMP in RPMC, when NaSal (1 mm) was added, transiently and significantly increased about sixfold compared with that of basal cells. These results suggest a possible use of NaSal in managing mast cell-dependent anaphylaxis.
 ...
PMID:Inhibition of mast cell-dependent anaphylaxis by sodium salicylate. 1023 41

This review summarizes our studies on the molecular biology of prostaglandin (PG) receptors and L-histidine decarboxylase (HDC). Regarding PG receptors, we have cloned five basic PG receptors (DP, EP, FP, IP, TP) and four EP subtypes (EP1-EP4). The PG receptors are divided into three families related to signal transduction systems of the receptors; Gs-couple group (IP, DP, EP2 and EP4), Gq-couple group (TP, FP and EP1), and Gi-couple group (EP3 and its isoform). EP3 isoforms having different C-terminal peptides can couple to distinct G proteins (Gi, Gs, Gq). Tissue specific expression of EP subtype mRNAs was observed in various organs. The phenotypic changes of mice deficient in each receptor are; the abnormal labor in FP-deficient mice, the failure of febrile response in EP3-deficient mice, the abnormal closure of ductus arteriosus after birth in EP4-deficient mice, and the impaired inflammatory swelling and pain responses in IP-deficient mice. Regarding HDC, we have purified mouse HDC from mastocytoma cells, which is a dimer of 53 kDa subunit, and then cloned its cDNA. The size of a cDNA-deduced HDC is 74 kDa. In the rat mast cell line, the endogenous 74 kDa form of HDC was translated in the cytosol and then translocated to the ER, where it was post-translationally processed to the 53 kDa form. On the other hand, the cytosolic 74 kDa form was rapidly degraded by an ATP/ubiquitin-dependent proteasome system. The 74 kDa form without on N-terminal signal sequence is inserted into the ER membrane with a C-terminal segment.
 ...
PMID:[Molecular biology of prostaglandin receptor and L-histidine decarboxylase]. 1051 17

To investigate the regulation of mouse L-histidine decarboxylase (HDC) gene expression, we isolated genomic DNA clones encoding HDC. Structural analysis revealed that the mouse HDC gene was composed of 12 exons, spanning approximately 24 kb. Northern blotting analysis indicated that, among the cell lines examined, a high level of HDC gene expression was restricted to mature mast cell lines and an erythroblastic cell line. The gene was induced strongly in the mouse immature mast cell line P815 after incubation in the peritoneal cavity of BDF1 mice. We observed that the promoter region was demethylated in the HDC-expressing cell lines and in induced P815 cells. Interestingly, forced demethylation by 5-azacytidine (5-azaC) treatment induced high expression of HDC mRNA in P815 cells. The activity of a mouse HDC promoter-reporter construct stably transfected in P815 cells was repressed by in vitro patch-methylation. This low promoter activity of the patch-methylated reporter construct was restored after 5-azaC treatment, which demethylated the patch-methylated promoter. These results indicate that DNA methylation state of the promoter region controls HDC gene expression.
 ...
PMID:The mouse L-histidine decarboxylase gene: structure and transcriptional regulation by CpG methylation in the promoter region. 1090 16

Histidine decarboxylase (HDC) synthesizes histamine from histidine in mammals. To evaluate the role of histamine, we generated HDC-deficient mice using a gene targeting method. The mice showed a histamine deficiency and lacked histamine-synthesizing activity from histidine. These HDC-deficient mice are viable and fertile but exhibit a decrease in the numbers of mast cells while the remaining mast cells show an altered morphology and reduced granular content. The amounts of mast cell granular proteases were tremendously reduced. The HDC-deficient mice provide a unique and promising model for studying the role of histamine in a broad range of normal and disease processes.
 ...
PMID:Mice lacking histidine decarboxylase exhibit abnormal mast cells. 1147 47

Histidine decarboxylase (HDC) synthesizes endogenous histamine from histidine in mammals. To evaluate the role of histamine in skin allergic reaction, we used HDC gene knockout mice lacking histamine. No plasma extravasation reaction was observed in HDC-/- mice after passive cutaneous anaphylaxis (PCA) test. Compound 48/80, a mast cell granule depletor, produced plasma extravasation inHDC+/+ mice but no extravasation in HDC-/- mice. Interestingly, orally administered histamine was distributed in the skin in HDC-/- mice and in these histamine-supplemented mice the plasma extravasation reaction was observed after the injection of compound 48/80 and the PCA test. Cultured bone marrow-derived mast cells of HDC-/- mice took up histamine from the histamine-supplemented medium into the secretory granules. The absorbed histamine was released in response to the same antigen and antibody combination used as in PCA test. In contrast to the immediate-type response, the delayed-type hypersensitive response, observed as a thickening of the ear skin after trinitrochlorobenzene challenge (following sensitization), showed no differences between HDC+/+ and HDC-/- mice. Therefore, among the allergic skin reactions, histamine is revealed to be an important mediator especially for the plasma extravasation in an immediate-type allergy model.
 ...
PMID:Plasma extravasation induced by dietary supplemented histamine in histamine-free mice. 1211 53

Because the Falck-Hillarp formaldehyde fluorescence method, which was superbly applied to identify catecholaminergic and serotonergic neurons, is not applicable to histamine, the first author (T.W.) developed an antibody to L-histidine decarboxylase (HDC) for identification of the histaminergic neuron system in the brain. The anti-HDC antibody was of great use for mapping the location and distribution of this histaminergic neuron system. (S)-alpha-fluoromethylhistidine, a specific and potent irreversible inhibitor of HDC, was also very useful in studies on functions of the neuron system. The activity of HDC is increased by various agents, treatments, and physiological conditions. We found new compounds that increased HDC activity (i.e., tetradecanoylphobol acetate (TPA), other tumor promoters, and staphylococcal enterotoxin A); and using mast cell-deficient mutant (W/W(v)) mice, we obtained evidence that this increase occurred in macrophages. To further characterize the mechanism of increases in HDC activity, the second author (H.O.) cloned human HDC cDNA and a human HDC gene. In studies on the regulation mechanism of the HDC gene, which is expressed only in limited types of cells such as mast cells, enterochromaffin-like cells in the stomach, cells in the tuberomammillary nucleus of the brain, and macrophages, CpG islands in the promoter region of the HDC gene were found to be demethylated in cells expressing the gene, whereas they are methylated in other cells that do not express the HDC gene. In collaboration with many other researchers, we developed HDC knockout mice. The resulting research is producing a lot of interesting findings in our laboratory as well as in others. In summary, HDC has been and will be useful in studies on functions of histamine.
 ...
PMID:L-histidine decarboxylase as a probe in studies on histamine. 1246 48

1. The aim of this study was to investigate the co-localization of histamine and dopamine-beta-hydroxylase in the superior cervical ganglion of guinea-pig and release of histamine from cardiac sympathetic terminals in guinea-pig isolated atrium. 2. Histidine decarboxylase (a histamine-synthesizing enzyme) mRNA signals were detected in the neurones of superior cervical ganglion of guinea-pig by in situ hybridization. The results of double-labelled immunofluorescence further confirmed the co-localization of histamine and dopamine-beta-hydroxylase in the large principle neurons and small intensely fluorescent cells in the superior cervical ganglion. The immunoreactivities of both histamine and dopamine-beta-hydroxylase were significantly attenuated after 6-hydroxydopamine-induced lesion of sympathetic nerves. 3. The refractory electrical field stimulation caused the release of histamine from cardiac sympathetic terminals of guinea-pig isolated atria (112.14 +/- 40.34 ng x ml(-1)), which was significantly attenuated to 35 +/- 15.57 ng x ml(-1) by reserpine pretreatment. Following administering compound 48/80, a mast cell degranulator, electrical field stimulation induced a dramatic increase of endogenous histamine release from isolated atria (303.57 +/-72.93 ng x ml(-1)). When compound 48/80 was added to the reserpine-treated atria, the release of histamine induced by field stimulation was decreased to 207.14 +/- 76.39 ng x ml(-1). 4 These results provide novel evidence that histamine co-exists with noradrenaline in sympathetic nerves and might act as a neurotransmitter to modulate sympathetic neurotransmission.
 ...
PMID:Co-localization of histamine and dopamine-beta-hydroxylase in sympathetic ganglion and release of histamine from cardiac sympathetic terminals of guinea-pig. 1525 17

Histamine is produced by mast cells and many other types of cells. The role of histamine released from mast cells in promoting tumor angiogenesis has been intensively studied; however, the role of non-mast cell histamine in regulating tumor angiogenesis has been largely ignored. In this study, tissue specimen sections from 43 patients with esophageal squamous cell carcinoma (ESCC) and normal esophageal biopsies from 17 heath individuals obtained from a high incidence area of north China were used to assess changes in microvessel density (MVD) and non-mast cell L-histidine decarboxylase (HDC) (the only rate-limiting enzyme that catalyzes the formation of histamine from L-histidine) expression in the tumor microenvironment by immunohistochemistry (IHC). In addition, the cellular characterization of non-mast cell HDC-positive cells in microvessels was examined by double IHC combined with HDC/CD34 and HDC/PCNA antibodies. These IHC analyses revealed a significantly increased HDC-positive MVD in ESCC as compared with normal controls, which accounted for approximately 61% of CD34-labeled general MVD in ESCC. Furthermore, IHC in serial sections and double IHC showed that most of these HDC-positive cells were CD34-positive endothelial cells in microvessels with an increased proliferative capacity. Thus, our results suggest that non-mast cell histamine expressed in endothelial cells of microvessels could be an additional cellular source and might play a role in regulating angiogenesis in ESCC.
 ...
PMID:Expression of non-mast cell histidine decarboxylase in tumor-associated microvessels in human esophageal squamous cell carcinomas. 1913 5


<< Previous 1 2 3 Next >>