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Histidine Decarboxylase (histidine + decarboxylase)
Selected AbstractsDevelopment of Amygdaloid Kindling in Histidine Decarboxylase,deficient and Histamine H1 Receptor,deficient MiceEPILEPSIA, Issue 4 2004Tadashi Hirai Summary: Purpose: This study attempted to clarify the role of histamine or histamine H1 receptors in the development of amygdaloid kindling by using histidine decarboxylase (HDC)-deficient and histamine H1 receptor (H1R)-deficient mice. Methods: Under pentobarbital anesthesia, mice were fixed to a stereotaxic apparatus, and bipolar electrodes were implanted into the right amygdala. Electrodes were connected to a miniature receptacle, which was embedded in the skull with dental cement. A bipolar electroencephalogram was recorded; bipolar stimulation of the amygdala was applied every day with a constant-current stimulator and continued until a generalized convulsion was obtained. Results: The development of amygdaloid kindling in HDC-deficient and H1R-deficient mice was significantly accelerated compared with that in their respective wild-type mice. In addition, the afterdischarge (AD) duration and generalized seizure duration in HDC-deficient and H1R-deficient mice were prolonged. Intraperitoneal injection of histidine resulted in an inhibition of amygdaloid kindled seizures in wild-type mice at doses that caused an increase in the histamine contents of the brain. However, no significant effect was observed with histidine in H1R-deficient mice at the same dose. Conclusions: These findings suggest that histaminergic mechanisms through H1 receptors play a crucial role not only in amygdaloid kindled seizures but also in the development of amygdaloid kindling. [source] Expression of histamine receptors and effect of histamine in the rat carotid body chemoafferent pathwayEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2006Nikolai Lazarov Abstract Chemosensory information from peripheral arterial oxygen sensors in the carotid body is relayed by petrosal ganglion neurons to the respiratory networks in the medulla oblongata. Biogenic amines, including histamine, released from glomus (type I) cells of the carotid body are considered to be primary transmitters in hypoxic chemosensitivity. Immunocytochemistry at light-and electron-microscopical levels, and RT-PCR, revealed the expression of histamine receptors 1 and 3 as well as histidine decarboxylase in the rat carotid body glomus cells and petrosal ganglion neurons. Histamine receptors 1 and 3, but not histidine decarboxylase, were also observed in the ventrolateral, intermediate and commissural subnuclei of the nucleus tractus solitarii in the medulla oblongata. In order to examine the possible role of histamine in the afferent branch of the respiratory system, we applied histamine receptor 1 and 3 agonists to the carotid body, which caused a mildly increased phrenic nerve activity in a working heart,brainstem preparation. Moreover, microinjection of antagonists of histamine receptors 1 and 3 into the nucleus tractus solitarii caused significant changes in the inspiratory timing and the chemoreceptor response. Our data show that histamine acting via histamine receptors 1 and 3 plays an important neuromodulatory role in the afferent control of chemosensitivity. [source] Differential expression of mast cell characteristics in human myeloid cell linesEXPERIMENTAL DERMATOLOGY, Issue 9 2004Pia Welker Abstract:, In order to better understand the mechanisms governing display of mast cell characteristics in human myeloid cells, we have studied the mast cell phenotype in human promyelocytic (HL-60) and myelocytic (U-937, TPH-1) vs. basophilic (KU-812) and mast cell (HMC-1) lines, in part also in skin mast cells and blood monocytes, at mRNA and protein level before and after stimulation with mast cell growth factors. In unstimulated cells, mRNA for the stem cell factor (SCF) receptor c-kit and the gamma chain of the high-affinity IgE receptor (Fc,RI) was noted in all cells studied. Like mast and basophilic cells, THP-1 cells expressed the Fc,RI, and , chains and weakly histidine decarboxylase (HDC), but they lacked mRNA for mast cell-specific proteases [tryptase, chymase, carboxypeptidase A (CPA)]. In contrast, HL-60 and U-937 cells lacked Fc,RI,, but expressed tryptase and chymase, HL-60 cells also CPA. KU-812 cells failed to express the basophil-specific marker 2D7. After a 10-day culture with SCF or fibroblast supernatants, baseline mRNA expression of most mast cell characteristics was upregulated, whereas c-kit mRNA expression decreased in all but THP-1 cells. Differential mRNA expression of Fc,RI vs. protease (tryptase) was confirmed at protein level by immunocytochemistry and enzymatic activity. KU-812 cells are thus closest to skin mast cells in that they express all molecules studied, except for chymase, followed by THP-1 cells that lack all mast cell proteases. In contrast, HL-60 and U-937 cells fail to express the Fc,RI, and , chains but express most mast cell proteases. The selective and differential expression of mast cell characteristics in human myeloid cell lines suggests that induction of the mast cell phenotype is regulated by several independent genes and that mast cells and basophils branch off at early and distinct points of myeloid development. [source] Chemical Coding of GABAB Receptor-Immunoreactive Neurones in Hypothalamic Regions Regulating Body WeightJOURNAL OF NEUROENDOCRINOLOGY, Issue 1 2003M. Bäckberg Abstract ,-aminobutyric acid (GABA) interacts with hypothalamic neuronal pathways regulating feeding behaviour. GABA has been reported to stimulate feeding via both ionotropic GABAA and metabotropic GABAB receptors. The functional form of the GABAB receptor is a heterodimer consisting of GABAB receptor-1 (GABABR1) and GABAB receptor-2 (GABABR2) proteins. Within the heterodimer, the GABA-binding site is localized to GABABR1. In the present study, we used an antiserum to the GABABR1 protein in order to investigate the cellular localization of GABABR1-immunoreactive neurones in discrete hypothalamic regions implicated in the control of body weight. The colocalization of GABABR1 immunoreactivity with different chemical messengers that regulate food intake was analysed. GABABR1-immunoreactive cell bodies were found in the periventricular, paraventricular (PVN), supraoptic, arcuate, ventromedial hypothalamic, dorsomedial hypothalamic, tuberomammillary nuclei and lateral hypothalamic area (LHA). Direct double-labelling showed that glutamic acid decarboxylase (GAD)-positive terminals were in close contact with GABABR1-containing cell bodies located in all these regions. In the ventromedial part of the arcuate nucleus, GABABR1-immunoreactive cell bodies were found to contain neuropeptide Y, agouti-related peptide (AGRP) and GAD. In the ventrolateral part of the arcuate nucleus, GABABR1-immunoreactive cell bodies were shown to contain pro-opiomelanocortin and cocaine- and amphetamine-regulated transcript. In the LHA, GABABR1 immunoreactivity was present in both melanin-concentrating hormone- and orexin-containing cell populations. In the tuberomammillary nucleus, GABABR1-immunoreactive cell bodies expressed histidine decarboxylase, a marker for histamine-containing neurones. In addition, GAD and AGRP were found to be colocalized in some nerve terminals surrounding GABABR1-immunoreactive cell bodies in the parvocellular part of the PVN. The results may provide a morphological basis for the understanding of how GABA regulates the hypothalamic control of food intake and body weight via GABAB receptors. [source] Histamine H4 receptor antagonist ameliorates chronic allergic contact dermatitis induced by repeated challengeALLERGY, Issue 3 2010M. Seike To cite this article: Seike M, Furuya K, Omura M, Hamada-Watanabe K, Matsushita A, Ohtsu H. Histamine H4 receptor antagonist ameliorates chronic allergic contact dermatitis induced by repeated challenge. Allergy 2010; 65: 319,326. Abstract Background:, The present study observed effects of the histamine H4 receptor on chronic allergic contact dermatitis induced by repeated challenge in mice. Methods:, Acute contact dermatitis was induced by single epicutaneous challenge of 2,4,6-trinitro-1-chlorobenzene (TNCB) to the ear. Chronic allergic contact dermatitis was developed by repeated epicutaneous challenge using TNCB on the dorsal back skin. H4 receptor antagonist JNJ7777120 was administered to wild-type mice, while H4 receptor agonist 4-methylhistamine was administered to histidine decarboxylase (HDC) (,/,) mice that synthesized no histamine. Results:, HDC (,/,) mice did not differ phenotypically from HDC (+/+) mice, and H4 receptor antagonist/agonist did not have clinical effects in terms of acute contact dermatitis reactions. H4 receptor antagonist ameliorated skin eczematous lesions induced by repeated TNCB challenge in HDC (+/+) mice. On the contrary, H4 receptor agonist exacerbated skin lesions exclusively in HDC (,/,) mice. Application of H4 receptor agonist induced migration of mast cells and eosinophils in skin lesions, and H4 receptor antagonist suppressed these changes. H4 receptor was immunohistochemically detected on mast cells in eczematous lesions. Levels of interleukin (IL)-4, -5, and -6 in lesions were decreased, whereas levels of interferon-, and IL-12 were increased by H4 receptor antagonistic activity. Serum Immunoglobulin E levels rapidly increased with repeated challenge, but decreased with H4 receptor antagonist. Conclusion:, Because chronic allergic contact dermatitis is developed by H4 receptor stimulation, H4 receptor antagonists might represent new candidate drugs for treating chronic allergic contact dermatitis. [source] Acute inflammatory reactions caused by histamine via monocytes/macrophages chronically participate in the initiation and progression of atherosclerosisPATHOLOGY INTERNATIONAL, Issue 7 2004Satoshi Kimura Previously we demonstrated that histidine decarboxylase (HDC), which produces histamine from l -histidine, was detected in monocytes/macrophages located in human atherosclerotic lesions. As monocytic migration is a key event of atherogenesis, we investigated whether histamine induces monocytic expression of monocyte chemoattractant protein (MCP)-1 and its receptors CCR2-A and -B, and also endothelial expression of ICAM-1 and VCAM-1. Furthermore, we studied the effect of interleukin (IL)-4, which inhibits the HDC expression, on the expression of MCP-1 and CCR2. Histamine stimulated monocytes, but not macrophages, to express MCP-1 and CCR2-A and -B. The expression of MCP-1 was inhibited by histamine H2 blocker. In contrast, IL-4 enhanced CCR2 expression but not MCP-1. Histamine stimulated endothelial cells to express ICAM-1 and VCAM-1. These results indicate that histamine and IL-4, which are both synthesized in the arterial intima, chronically participates in the pathogenesis of atherosclerosis via the enhanced expression of monocytic MCP-1, CCR2 and endothelial adhesion molecules. [source] Expression of non-mast cell histidine decarboxylase in tumor-associated microvessels in human esophageal squamous cell carcinomas,APMIS, Issue 12 2008ZHENFENG LI 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 ,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. [source] Pharmacological effects of carcinine on histaminergic neurons in the brainBRITISH JOURNAL OF PHARMACOLOGY, Issue 5 2004Zhong Chen Carcinine (, -alanyl histamine) is an imidazole dipeptide. The present study was designed to characterize the pharmacological effects of carcinine on histaminergic activity in the brain and on certain neurobehavior. Carcinine was highly selective for the histamine H3 receptor over H1 or H2 receptor (Ki (,M)=0.2939±0.2188 vs 3621.2±583.9 or 365.3±232.8 ,M, respectively). Carcinine at a dose of 20 mg kg,1 slightly increased histidine decarboxylase (HDC) activity in the cortex (from 0.186±0.069 to 0.227±0.009 pmol mg protein,1 min,1). In addition, carcinine (10, 20, and 50 mg kg,1) significantly decreased histamine levels in mice brain. Like thioperamide, a histamine H3 receptor antagonist, carcinine (20, 50 ,M) significantly increased 5-HT release from mice cortex slices, but had no apparent effect on dopamine release. Carcinine (20 mg kg,1) significantly inhibited pentylenetetrazole-induced kindling. This inhibition was completedly reversed by (R)- , -methylhistamine, a representative H3 receptor agonist, and , -fluromethylhistidine, a selective HDC inhibitor. Carcinine (20 mg kg,1) ameliorated the learning deficit induced by scopolamine. This amelioration was reversed by (R)- , -methylhistamine as evaluated by the passive avoidance test in mice. Like thioperamide, carcinine dose-dependently increased mice locomotor activity in the open-field test. The results of this study provide first and direct evidence that carcinine, as a novel histamine H3 receptor antagonist, plays an important role in histaminergic neurons activation and might be useful in the treatment of certain diseases, such as epilepsy, and locomotor or cognitive deficit. British Journal of Pharmacology (2004) 143, 573,580. doi:10.1038/sj.bjp.0705978 [source] | ||||||||||