Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It was reported recently that histamine induced Toll-like receptor (TLR)2 and TLR4 expression in endothelial cells and enhanced their sensitivity to Gram-positive and Gram-negative bacteria; and that TLRs were expressed in airway epithelial cells and that several inflammatory mediators modulated their expression. However, little is known of potential influence of histamine on TLRs in pulmonary epithelial cells. In the present study, effects of histamine on expression of TLRs in both human A549 and NCI-H292 cell lines were examined by using real-time quantitative RT-PCR analysis, flow cytometry and immunofluorescent staining. The results revealed that both cell types constitutively expressed mRNAs for TLR1-TLR10. Histamine up-regulated the expression of TLR3 mRNA by 12.3- and 11.6-fold, respectively in both cell types. The time course showed that histamine induced TLR3 mRNA expression was initiated at 30 min, nearly reached peak levels after 2 h and was sustained at least until 12 h. Histamine also induced TLR3 protein expression in A549 and NCI-H292 cells. Histamine and poly (I:C), a specific TLR3 ligand stimulated interleukin (IL)-8 secretion from both cell types. Moreover, histamine enhanced poly (I:C)-induced IL-8 secretion and phosphorylation of NF-kappaB in the two cell types, and histamine H1 receptor antagonists inhibited the action of histamine. In conclusion, histamine selectively up-regulated expression of TLR3, and stimulated IL-8 secretion from the cells. Histamine also enhanced poly (I:C) induced IL-8 secretion and phosphorylation of NF-kappaB. These observations suggest that histamine might play an important role in enhancing the innate immune responses of airway to viral infection.
Mol Immunol 2006 May
PMID:Modulation of expression and function of Toll-like receptor 3 in A549 and H292 cells by histamine. 1640 95

Recombinant proteins are used for vaccines, therapy and diagnosis of many diseases. Biological activity of these may differ from native counterpart and needs investigation. The present study aimed to compare recombinant (r) and native (n) glutathione-S-transferase (GST) from Alternaria alternata. Glutathione-S-transferase sequence showed an ORF of 696bp encoding 26-kDa protein with N-terminus conserved domain. Secondary structure of both forms was comparable with melting temperature of 57 and 59 degrees C, respectively. rGST and nGST showed similar enzymatic activity, allergenicity and potency by ELISA inhibition. Histamine release was comparable in 14/17 patients for both the GSTs. rGST and nGST induced proliferation in PBMC at different concentration. Cell supernatant revealed higher IL-4 and IL-5 levels with low levels of IFN-gamma. In summary, recombinant and native GST demonstrated similar physio-chemical, biological and immunological properties and induced comparable cell mediated and humoral response to be used for diagnosis and specific immunotherapy for the fungal allergy cases.
Mol Immunol 2006 May
PMID:Recombinant glutathione-S-transferase a major allergen from Alternaria alternata for clinical use in allergy patients. 1643 Sep 61

Histamine is a well-known mediator eliciting a broad range of responses in different cell types. Four different subtypes of G protein-coupled histamine receptors (H1-H4) have been cloned and pharmacologically characterized. However, involvement of the different histamine receptor subtypes in immunomodulatory functions of bronchial epithelium has only been investigated marginally. The expression and function of histamine receptor subtypes on the human bronchial epithelial cell line BEAS-2B was analyzed by PCR, intracellular Ca++ -measurements and ELISA. We show mRNA expression of the histamine receptor subtypes H1, H2, and H3, but not H4 in the human bronchial epithelial cell line BEAS-2B. Using intracellular Ca++ -measurements, we demonstrated functional expression of the H1 and H3 receptors. To characterize the biological properties of histamine in airway epithelial biology, we also investigated its effects on cytokine secretion by BEAS-2B cells. Thereby, we were able to show up-regulation of the proinflammatory mediators IL-6 and CXCL8/ IL-8 via activation of the H1, H2 and H3 receptor subtypes. The Th1 cytokines CXCL9/MIG and CXCL10/IP-10 and the chemokine CCL5/RANTES were regulated in a distinct manner: Whereas histamine inhibited the IFN-gamma/TNF-alpha-induced secretion of MIG via the histamine receptor subtypes H1, H2, and H3, the histamine-induced suppression of RANTES was due to activation of the H2 and H3 receptors, while reduction of cytokine-triggered IP-10 secretion was mediated only by triggering the H2 receptor. In summary our data provide evidence that histamine released during allergic lung diseases exerts regulatory influence on airway epithelial cells.
Int J Mol Med 2006 Nov
PMID:Functional characterization of histamine receptor subtypes in a human bronchial epithelial cell line. 1701 23

The present study investigated whether cAMP-dependent cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel current (i.e., I(Cl.CFTR) or I(Cl.cAMP)) would be expressed in pig cardiac myocytes using whole-cell patch technique and reverse transcription polymerase chain reaction (RT-PCR). It was found that the beta-adrenoceptor agonist isoproterenol activated a time-independent current in myocytes from the ventricle, but not the atrium of pig heart. Histamine and forskolin (an adenylate cyclase activator) induced a similar current in pig ventricular cells. The current induced by isoproterenol was blocked by the PKA inhibitor H-7, reduced by the replacement of external Cl(-) ion, and inhibited by the application of 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB), but not 4'-diisothiocynatostilbene-2,2'-disulfonic acid (DIDS), typical of I(Cl.CFTR). I(Cl.CFTR) showed a small difference in regional myocytes across the left ventricular wall from epicardium to endocardium. Isoproterenol-induced current was 3.1+/-0.2 (n=33), 2.8+/-0.2 (n=25) and 2.3+/-0.2 pA/pF (n=31) respectively in subepicardial, midmyocardial, and subendocardial myocytes (P<0.05, subepicardium vs. subendocardium). RT-PCR and Western blotting analysis revealed that significant differences in CFTR channel mRNA and protein levels were present in atrial and ventricular cells, but not in regional ventricular cells across the ventricular wall from subepicardium to subendocardium. These results indicate that the functional CFTR channel (i.e., I(Cl.CFTR)) is present in ventricular myocytes, but not in atrial cells of pig heart.
J Mol Cell Cardiol 2007 Jan
PMID:Evidence for cystic fibrosis transmembrane conductance regulator chloride current in swine ventricular myocytes. 1711 38

Histamine might have an important role in brain development. However, most studies have focused on short-term effects of histamine receptor-mediated signaling on brain function in adulthood. Little is known about the potential long-term effects of histamine receptor-mediated signaling during development on brain function in adulthood. We hypothesize that increased postsynaptic histamine receptor-mediated signaling during development has detrimental effects on brain function in adulthood. Our data support this hypothesis. In the developing mouse brain, histamine H3 receptor blockade, which increases histamine release, has detrimental sex-dependent effects on object recognition, spatial learning in the water maze, and pre-pulse inhibition in adulthood. Our data also support the hypothesis that histamine mediates the detrimental long-term sex-dependent effects of methamphetamine exposure early in life on these brain functions in adulthood. Therefore, increased efforts are warranted to carefully evaluate the effects of drugs that directly or indirectly affect histamine receptor-mediated signaling during development on cognitive function later in life.
Cell Mol Life Sci 2007 Mar
PMID:Histamine receptor-mediated signaling during development and brain function in adulthood. 1731 Feb 79

1. The present study aimed at elucidating the effect of nitric oxide (NO) on blood-brain barrier (BBB) function with mouse brain capillary endothelial (MBEC4) cells.2. Histamine (20-100 microM) evoked NO production (1.6-7 microM) in MBEC4 cells in a dose-dependent manner.3. The permeability coefficient of sodium fluorescein for MBEC4 cells and the cellular accumulation of rhodamine 123 in MBEC4 cells were increased dose-dependently by the addition of NO solutions (14 and 28 microM) every 10 min during a 30-min period.4. The present study demonstrated that NO increased the permeability and inhibited the P-glycoprotein efflux pump of brain capillary endothelial cells, suggesting that NO plays an inhibitory role in the dynamic regulation of the BBB function.
Cell Mol Neurobiol 2007 May
PMID:An inhibitory role of nitric oxide in the dynamic regulation of the blood-brain barrier function. 1731 83

Histamine (HA) is one of many neurotransmitters that have been implicated in cardiovascular functioning. Alterations in vascular smooth muscle due to the effects of histamine have been suggested. We investigated the modulatory effect of HA on mitogen activated protein kinase (MAPK) expression, specifically extracellular regulating kinase (ERK) 1 & 2 in vascular smooth muscle cells (VSMCs) from both spontaneously hypertensive (SHR) and control Wistar Kyoto (WKY) rats. Cross-talking between calcium (Ca2+) and HA during HA-induced modulatory effect on MAPK expression in SHR VSMCs was also investigated. A stimulatory increase in expression of ERK 1 & 2 was observed to be dose and time dependent with maximum expression occurring within 5 min in both SHR and WKY VSMCs. The stimulatory increase in expression is persistent for 60 min in SHR VSMCs, whereas, in WKY cells the stimulatory effect persists for only 20 min. Mepyramine, the H1 receptor antagonist, reduced the HA-induced increase in ERK 1 & 2 significantly in SHR VSMCs. A reduction in the HA stimulated increase in ERK 1 & 2 expression was observed at 20 min of exposing cells to diltiazem, the calcium channel blocker, whereas, the calcium chelator, BAPTA effect on ERK 1 & 2 expression was observed within 5 min in SHR VSMCs. The data demonstrates that cross-talking occurs between HA stimulation and Ca2+ induction during HA-induced activation of ERK 1 & 2 in VSMCs of both cell types. Although both intracellular calcium ([Ca2+]i) and extracellular Ca2+ maybe involved in the activation of ERK 1 & 2 by HA, the dependence on [Ca2+]i is more dramatic than the dependence on extracellular Ca2+ in hypertensive cells, which may contribute to the role of HA as a risk factor of hypertension in VSMCs of the aorta.
Cell Mol Biol (Noisy-le-grand) 2007 May 15
PMID:Cross-talking between calcium and histamine in the expression of MAPKs in hypertensive vascular smooth muscle cells. 1753 Nov 62

Histamine H3 receptors are presynaptic autoreceptors found in both central and peripheral nervous systems of many species. The central effects of these receptors suggest a potential therapeutic role for their antagonists in treatment of several neurological disorders such as epilepsy, schizophrenia, Alzheimer's and Parkinson's diseases. The purpose of this study was to identify the structural requirements for H3 antagonistic activity via quantitative structure-activity relationship (QSAR) studies and receptor modeling/docking techniques. A combination of partial least squares (PLS) and genetic algorithm (GA) was used in the QSAR approach to select the structural descriptors relevant to the receptor binding affinity of a series of 58 H3 antagonists. The descriptors were selected out of a pool of >1000 descriptors calculated by DRAGON, Hyperchem and ACD labs suite of programs. The resulting QSAR models for rat and human H3 binding affinities were validated using different strategies. QSAR models generated in the current work suggested the role of charge transfer interactions in the ligand-receptor interaction verified using the molecular modeling of the receptor and docking two antagonists to the binding site. The 3D model of human H3 receptor was built based on bovine rhodopsin structure and evaluated by molecular dynamics (MD) simulation in a mixed water-vacuum-water environment. The results were indicative of the stability of the model relating the observed structural changes during the MD simulation to the suggested ligand-receptor interactions. The results of this investigation are expected to be useful in the process of design and development of new potent H3 receptor antagonists.
J Mol Graph Model 2008 Jan
PMID:Molecular modeling of histamine H3 receptor and QSAR studies on arylbenzofuran derived H3 antagonists. 1756 22

The Histamine H(1)-receptor (H1R), belonging to the amine receptor-class of family A of the G-protein coupled receptors (GPCRs) gets activated by agonists. The consequence is a conformational change of the receptor, which may involve the binding-pocket. So, for a good prediction of the binding-mode of an agonist, it is necessary to have knowledge about these conformational changes. Meanwhile some experimental data about the structural changes of GPCRs during activation exist. Based on homology modeling of the guinea-pig H1R (gpH1R), using the crystal structure of bovine rhodopsin as template, we performed several MD simulations with distance restraints in order to get an inactive and an active structure of the gpH1R. The calculations led to a Phe6.44/Trp6.48/Phe6.52-switch and linearization of the proline kinked transmembrane helix VI during receptor activation. Our calculations showed that the Trp6.48/Phe6.52-switch induces a conformational change in Phe6.44, which slides between transmembrane helices III and VI. Additionally we observed a hydrogen bond interaction of Ser3.39 with Asn7.45 in the inactive gpH1R, but because of a counterclockwise rotation of transmembrane helix III Ser3.39 establishes a water-mediated hydrogen bond to Asp2.50 in the active gpH1R. Additionally we simulated a possible mechanism for receptor activation with a modified LigPath-algorithm.
J Comput Aided Mol Des 2007 Sep
PMID:Analysis of the activation mechanism of the guinea-pig Histamine H1-receptor. 1771 99

(1) The present study was designed to investigate whether histamine is involved in the protective effect of carnosine on Abeta42-induced impairment in differentiated PC12 cells. (2) PC12 cells were exposed to Abeta42 (5 muM) for 24 h after carnosine (5 mM) applied for 18 h. Histamine receptor antagonists (diphenhydramine, zolantidine, thioperamide, clobenpropit) or histidine decarboxylase inhibitor (alpha-fluoromethylhistidine) were added 15 min before carnosine. Cell viability, glutamate release or cell surface expression of NMDA receptor was examined. (3) Abeta42 caused a concentration-dependent reduction of viability in PC12 cells and pretreatment with carnosine ameliorated this impairment. This amelioration was reversed by the H(3) receptor antagonists thioperamide and clobenpropit, but not by either the H(1) receptor antagonist diphenhydramine or the H(2) receptor antagonist zolantidine. Further, alpha-fluoromethylhistidine, an irreversible inhibitor of histidine decarboxylase, also had no effect. In the presence of Abeta42, carnosine significantly decreased glutamate release and carnosine increased the surface expression of NMDA receptor. (4) These results indicate that the mechanism by which carnosine attenuates Abeta42-induced neurotoxicity is independent of the carnosine-histidine-histamine pathway, but may act through regulation of glutamate release and NMDA receptor trafficking.
Cell Mol Neurobiol 2008 Feb
PMID:Carnosine protects against Abeta42-induced neurotoxicity in differentiated rat PC12 cells. 1802 86


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