Structure-based prediction of subtype selectivity of histamine H3 receptor selective antagonists in clinical trials.

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Kim, Soo-Kyung; Fristrup, Peter; Abrol, Ravinder; Goddard, William A

2011-12-27

Histamine receptors (HRs) are excellent drug targets for the treatment of diseases, such as schizophrenia, psychosis, depression, migraine, allergies, asthma, ulcers, and hypertension. Among them, the human H(3) histamine receptor (hH(3)HR) antagonists have been proposed for specific therapeutic applications, including treatment of Alzheimer's disease, attention deficit hyperactivity disorder (ADHD), epilepsy, and obesity. However, many of these drug candidates cause undesired side effects through the cross-reactivity with other histamine receptor subtypes. In order to develop improved selectivity and activity for such treatments, it would be useful to have the three-dimensional structures for all four HRs. We report here the predicted structures of four HR subtypes (H(1), H(2), H(3), and H(4)) using the GEnSeMBLE (GPCR ensemble of structures in membrane bilayer environment) Monte Carlo protocol, sampling ∼35 million combinations of helix packings to predict the 10 most stable packings for each of the four subtypes. Then we used these 10 best protein structures with the DarwinDock Monte Carlo protocol to sample ∼50 000 × 10(20) poses to predict the optimum ligand-protein structures for various agonists and antagonists. We find that E206(5.46) contributes most in binding H(3) selective agonists (5, 6, 7) in agreement with experimental mutation studies. We also find that conserved E5.46/S5.43 in both of hH(3)HR and hH(4)HR are involved in H(3)/ H(4) subtype selectivity. In addition, we find that M378(6.55) in hH(3)HR provides additional hydrophobic interactions different from hH(4)HR (the corresponding amino acid of T323(6.55) in hH(4)HR) to provide additional subtype bias. From these studies, we developed a pharmacophore model based on our predictions for known hH(3)HR selective antagonists in clinical study [ABT-239 1, GSK-189,254 2, PF-3654746 3, and BF2.649 (tiprolisant) 4] that suggests critical selectivity directing elements are: the basic proton

Histamine-2 receptor antagonist famotidine modulates cardiac stem cell characteristics in hypertensive heart disease

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Sherin Saheera

2017-10-01

Full Text Available Background Cardiac stem cells (CSCs play a vital role in cardiac homeostasis. A decrease in the efficiency of cardiac stem cells is speculated in various cardiac abnormalities. The maintenance of a healthy stem cell population is essential for the prevention of adverse cardiac remodeling leading to cardiac failure. Famotidine, a histamine-2 receptor antagonist, is currently used to treat ulcers of the stomach and intestines. In repurposing the use of the drug, reduction of cardiac hypertrophy and improvement in cardiac function of spontaneously hypertensive rats (SHR was reported by our group. Given that stem cells are affected in cardiac pathologies, the effect of histamine-2 receptor antagonism on CSC characteristics was investigated. Methods To examine whether famotidine has a positive effect on CSCs, spontaneously hypertensive rats (SHR treated with the drug were sacrificed; and CSCs isolated from atrial appendages was evaluated. Six-month-old male SHRs were treated with famotidine (30 mg/kg/day for two months. The effect of famotidine treatment on migration, proliferation and survival of CSCs was compared with untreated SHRs and normotensive Wistar rats. Results Functional efficiency of CSCs from SHR was compromised relative to that in Wistar rat. Famotidine increased the migration and proliferation potential, along with retention of stemness of CSCs in treated SHRs. Cellular senescence and oxidative stress were also reduced. The expression of H2R was unaffected by the treatment. Discussion As anticipated, CSCs from SHRs were functionally impaired. Stem cell attributes of famotidine-treated SHRs was comparable to that of Wistar rats. Therefore, in addition to being cardioprotective, the histamine 2 receptor antagonist modulated cardiac stem cells characteristics. Restoration of stem cell efficiency by famotidine is possibly mediated by reduction of oxidative stress as the expression of H2R was unaffected by the treatment. Maintenance of

Comparison of the tumor inhibiting effects of three histamine H2-receptor antagonists.

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Tutton, P J; Barkla, D H

1983-01-01

Three histamine H2-receptor antagonists, Cimetidine, Metiamide and Ranitidine, were tested for their inhibitory effect on two experimental bowel cancer models. In the first model mitotic rates were measured in dimethylhydrazine-induced tumors of rat colon and in the second model volumetric changes in human large bowel cancer xenografts were assessed. In tumors of rat colon all three drugs were able to suppress mitotic activity, but the effects of Metiamide and Ranitidine were more prolonged than that of Cimetidine in each of two lines of human bowel cancer that were used. Metiamide and Ranitidine were also more effective growth inhibitors than was Cimetidine.

Mutational analysis of the antagonist-binding site of the histamine H(1) receptor.

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Wieland, K; Laak, A M; Smit, M J; Kühne, R; Timmerman, H; Leurs, R

1999-10-15

We combined in a previously derived three-dimensional model of the histamine H(1) receptor (Ter Laak, A. M., Timmerman, H., Leurs, H., Nederkoorn, P. H. J., Smit, M. J., and Donne-Op den Kelder, G. M. (1995) J. Comp. Aid. Mol. Design. 9, 319-330) a pharmacophore for the H(1) antagonist binding site (Ter Laak, A. M., Venhorst, J., Timmerman, H., and Donné-Op de Kelder, G. M. (1994) J. Med. Chem. 38, 3351-3360) with the known interacting amino acid residue Asp(116) (in transmembrane domain III) of the H(1) receptor and verified the predicted receptor-ligand interactions by site-directed mutagenesis. This resulted in the identification of the aromatic amino acids Trp(167), Phe(433), and Phe(436) in transmembrane domains IV and VI of the H(1) receptor as probable interaction points for the trans-aromatic ring of the H(1) antagonists. Subsequently, a specific interaction of carboxylate moieties of two therapeutically important, zwitterionic H(1) antagonists with Lys(200) in transmembrane domain V was predicted. A Lys(200) --> Ala mutation results in a 50- (acrivastine) to 8-fold (d-cetirizine) loss of affinity of these zwitterionic antagonists. In contrast, the affinities of structural analogs of acrivastine and cetirizine lacking the carboxylate group, triprolidine and meclozine, respectively, are unaffected by the Lys(200) --> Ala mutation. These data strongly suggest that Lys(200), unique for the H(1) receptor, acts as a specific anchor point for these "second generation" H(1) antagonists.

Histamine-2 receptor antagonists as immunomodulators: new therapeutic views?

DEFF Research Database (Denmark)

Nielsen, Hans Jørgen

1996-01-01

Considerable evidence has emerged to suggest that histamine participates in the regulation of the inflammatory response, immune reaction, coagulation cascade, and cardiovascular function. Furthermore, histamine may play a major role in the growth of normal and malignant tissue as a regulator of p...

Characteristics of recombinantly expressed rat and human histamine H3 receptors.

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Wulff, Birgitte S; Hastrup, Sven; Rimvall, Karin

2002-10-18

Human and rat histamine H(3) receptors were recombinantly expressed and characterized using receptor binding and a functional cAMP assay. Seven of nine agonists had similar affinities and potencies at the rat and human histamine H(3) receptor. S-alpha-methylhistamine had a significantly higher affinity and potency at the human than rat receptor, and for 4-[(1R*,2R*)-2-(5,5-dimethyl-1-hexynyl)cyclopropyl]-1H-imidazole (Perceptin) the preference was the reverse. Only two of six antagonists had similar affinities and potencies at the human and the rat histamine H(3) receptor. Ciproxifan, thioperamide and (1R*,2R*)-trans-2-imidazol-4 ylcyclopropyl) (cyclohexylmethoxy) carboxamide (GT2394) had significantly higher affinities and potencies at the rat than at the human histamine H(3) receptor, while for N-(4-chlorobenzyl)-N-(7-pyrrolodin-1-ylheptyl)guanidine (JB98064) the preference was the reverse. All antagonists also showed potent inverse agonism properties. Iodoproxyfan, Perceptin, proxyfan and GR175737, compounds previously described as histamine H(3) receptor antagonists, acted as full or partial agonists at both the rat and the human histamine H(3) receptor. Copyright 2002 Elsevier Science B.V.

JB-9322, a new selective histamine H2-receptor antagonist with potent gastric mucosal protective properties.

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Palacios, B; Montero, M J; Sevilla, M A; Román, L S

1995-05-01

1. JB-9322 is a selective histamine H2-receptor antagonist with gastric antisecretory activity and mucosal protective properties. 2. The affinity of JB-9322 for the guinea-pig atria histamine H2-receptor was approximately 2 times greater than that of ranitidine. 3. In vivo, the ID50 value for the inhibition of gastric acid secretion in pylorus-ligated rats was 5.28 mg kg-1 intraperitoneally. JB-9322 also dose-dependently inhibited gastric juice volume and pepsin secretion. In gastric lumen-perfused rats, intravenous injection of JB-9322 dose-dependently reduced histamine-, pentagastrin- and carbachol-stimulated gastric acid secretion. 4. JB-9322 showed antiulcer activity against aspirin and indomethacin-induced gastric lesions and was more potent than ranitidine. 5. JB-9322 effectively inhibited macroscopic gastric haemorrhagic lesions induced by ethanol. Intraperitoneal injection was effective in preventing the lesions as well as oral treatment. The oral ID50 value for these lesions was 1.33 mg kg-1. By contrast, ranitidine (50 mg kg-1) failed to reduce these lesions. In addition, the protective effect of JB-9322 was independent of prostaglandin synthesis. 6. These results indicate that JB-9322 is a new antiulcer drug that exerts a potent cytoprotective effect in addition to its gastric antisecretory activity.

Fenspiride inhibits histamine-induced responses in a lung epithelial cell line.

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Quartulli, F; Pinelli, E; Broué-Chabbert, A; Gossart, S; Girard, V; Pipy, B

1998-05-08

Using the human lung epithelial WI26VA4 cell line, we investigated the capacity of fenspiride, an anti-inflammatory drug with anti-bronchoconstrictor properties, to interfere with histamine-induced intracellular Ca2+ increase and eicosanoid formation. Histamine and a histamine H1 receptor agonist elicited a rapid and transient intracellular Ca2+ increase (0-60 s) in fluo 3-loaded WI26VA4 cells. This response was antagonized by the histamine H1 receptor antagonist, diphenhydramine, the histamine H2 receptor antagonist, cimetidine, having no effect. Fenspiride (10(-7)-10(-5) M) inhibited the histamine H1 receptor-induced Ca2+ increase. In addition, histamine induced a biphasic increase in arachidonic acid release. The initial rise (0-30 s), a rapid and transient arachidonic acid release, was responsible for the histamine-induced intracellular Ca2+ increase. In the second phase release (15-60 min), a sustained arachidonic acid release appeared to be associated with the formation of cyclooxygenase and lipoxygenase metabolites. Fenspiride (10(-5) M) abolished both phases of histamine-induced arachidonic acid release. These results suggest that anti-inflammatory and antibronchoconstrictor properties of fenspiride may result from the inhibition of these effects of histamine.

Typical and Atypical Antipsychotic Drugs Increase Extracellular Histamine Levels in the Rat Medial Prefrontal Cortex: Contribution of Histamine H1 Receptor Blockade

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Kjell A Svensson

2012-05-01

Full Text Available Atypical antipsychotics such as clozapine and olanzapine have been shown to enhance histamine turnover and this effect has been hypothesized to contribute to their improved therapeutic profile compared to typical antipsychotics. In the present study, we examined the effects of antipsychotic drugs on histamine (HA efflux in the mPFC of the rat by means of in vivo microdialysis and sought to differentiate the receptor mechanisms which underlie such effects. Olanzapine and clozapine increased mPFC HA efflux in a dose related manner. Increased HA efflux was also observed after quetiapine, chlorpromazine and perphenazine treatment. We found no effect of the selective 5-HT2A antagonist MDL100907, 5-HT2c antagonist SB242084 or the 5-HT6 antagonist Ro 04-6790 on mPFC HA efflux. HA efflux was increased following treatment with selective H1 receptor antagonists pyrilamine, diphenhydramine and triprolidine, the H3 receptor antagonist ciproxifan and the mixed 5HT2A/H1 receptor antagonist ketanserin. The potential novel antipsychotic drug FMPD, which has a lower affinity at H1 receptors than olanzapine, did not affect HA efflux. Similarly, other antipsychotics with lower H1 receptor affinity (risperidone, aripiprazole and haloperidol were also without effect on HA efflux. Perfusion of clozapine and pyrilamine into the TMN, but not the mPFC, increased local HA efflux. Finally, HA efflux after antipsychotic treatment was significantly correlated with affinity at H1 receptors whereas 9 other receptors, including 5-HT2A, were not. These results demonstrate that both typical and atypical antipsychotics increase mPFC histamine efflux and this effect may be mediated via antagonism of histamine H1 receptors.

Histamine Potentiates Cyclosomatostatin-Induced Catalepsy in Old Rats

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Ionov

2015-05-01

Full Text Available Background The decreased level of somatostatin and increased level of histamine are detected in the Parkinsonian brain. In old Wistar rats, the brain somatostatin deficiency can initiate catalepsy that suggests the pathogenic significance of this abnormality in Parkinson’s disease (PD. The ability of histamine to affect the somatostatin deficiency action is not studied. Objectives The current study aimed to examine if histamine alters the cataleptogenic activity of the brain somatostatin deficiency in Wistar rats. Materials and Methods The animals used in the study were 100 - 110 and 736 - 767 days old. Catalepsy was evaluated by the bar test. The inhibition of the brain somatostatin activity was simulated by I.C.V. administration of cyclosomatostatin (cycloSOM, a somatostatin receptor antagonist. Results CycloSOM (0.2, 1.0, and 5.0 µg and histamine (1.0 and 10.0 µg alone were ineffective in both young and old animals. In combination, however, cycloSOM and histamine initiated cataleptic response in old rats. Effect of the combination was inhibited by H1 and H2 but not H3 antagonists. Conclusions CycloSOM and histamine synergistically exert catalepsy in old rats. In light of these data, the combination of the decreased brain level of somatostatin and increased brain level of histamine may be of pathogenic relevance for extrapyramidal signs in PD.

Involvement of prostaglandins and histamine in radiation-induced temperature responses in rats

International Nuclear Information System (INIS)

Kandasamy, S.B.; Hunt, W.A.

1990-01-01

Exposure of rats to 1-15 Gy of gamma radiation induced hyperthermia, whereas exposure to 20-150 Gy produced hypothermia. Since radiation exposure induced the release of prostaglandins (PGs) and histamine, the role of PGs and histamine in radiation-induced temperature changes was examined. Radiation-induced hyper- and hypothermia were antagonized by pretreatment with indomethacin, a cyclooxygenase inhibitor. Intracerebroventricular administration of PGE2 and PGD2 induced hyper- and hypothermia, respectively. Administration of SC-19220, a specific PGE2 antagonist, attenuated PGE2- and radiation-induced hyperthermia, but it did not antagonize PGD2- or radiation-induced hypothermia. Consistent with an apparent role of histamine in hypothermia, administration of disodium cromoglycate (a mast cell stabilizer), mepyramine (H1-receptor antagonist), or cimetidine (H2-receptor antagonist) attenuated PGD2- and radiation-induced hypothermia. These results suggest that radiation-induced hyperthermia is mediated via PGE2 and that radiation-induced hypothermia is mediated by another PG, possibly PGD2, via histamine

Effects of Bidens pilosa L. var. radiata SCHERFF treated with enzyme on histamine-induced contraction of guinea pig ileum and on histamine release from mast cells.

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Matsumoto, Takayuki; Horiuchi, Masako; Kamata, Katsuo; Seyama, Yoshiyuki

2009-06-01

The medical mechanism against type I allergies is to block the release or production of chemical mediators from mast cells or to block the H(1)-receptor signaling. We previously reported that the anti-allergic action of the dry powder from Bidens pilosa L. var. radiata SCHERFF treated with the enzyme cellulosine (eMMBP) was dependent on the inhibition of histamine release from mast cells. Here, we investigate that the effect of fractions in eMMBP on the histamine-induced contraction in guinea pig ileum and on the release of histamine in rat peritoneal mast cells. The histamine-induced contraction in guinea pig ileum is dose-dependently inhibited by ketotifen, an antagonist of H(1)-receptor. Fractions contained caffeic acid, caffeoylquinic acid and fractions contained flavonoids such as hyperin and isoquercitrin in eMMBP inhibit histamine release from mast cells, but only flavonoids such as hyperin, isoquercitrin and rutin suppress the histamine-induced contraction in guinea pig ileum. Moreover, the histamine-induced contraction was not affected by caffeic acid, however, such contraction was significantly inhibited by rutin. These results suggest that the primary antagonists of H(1)- receptor are different from the components in eMMBP that inhibit histamine release, and that these components participate in the anti-allergic activity of eMMBP.

Crystal structure of (OC5W(μ-dppeW(CO5

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Hannah F. Drake

2016-10-01

Full Text Available The centrosymmetric title complex, [μ-ethane-1,2-diylbis(diphenylphosphane-κ2P:P′]bis[pentacarbonyltungsten(0], [W2(C26H24P2(CO10], consists of two W(CO5 moieties bridged by a bis(diphenylphosphanylethane (dppe ligand. The W0 atom has a slightly distorted octahedral coordination environment consisting of 5 carbonyl ligands and one P atom from the bridging dppe ligand with the nearest W0 atom 5.625 (5 Å away. The complex resides on a center of symmetry.

Effects of a histamine H4 receptor antagonist on cisplatin-induced anorexia in mice.

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Yamamoto, Kouichi; Okui, Rikuya; Yamatodani, Atsushi

2018-04-12

Cancer chemotherapy often induces gastrointestinal symptoms such as anorexia, nausea, and vomiting. Antiemetic agents are effective in inhibiting nausea and vomiting, but patients still experience anorexia. We previously reported that chemotherapeutic agent-induced anorexia is associated with an increase of inflammatory cytokines. Other studies also reported that antagonism of the histamine H 4 receptor is anti-inflammatory. In this study, we investigated the involvement of the H 4 receptor in the development of chemotherapy-induced anorexia in mice. Cisplatin-induced anorexia occurred within 24 h of its administration and continued for 3 days. The early phase (day 1), but not the delayed phase (days 2 and 3), of anorexia was inhibited by the daily injection of a 5-HT 3 receptor antagonist (granisetron). However, a corticosteroid (dexamethasone) or selective H 4 receptor antagonist (JNJ7777120) abolished the delayed phases of anorexia. Cisplatin significantly increased TNF-α mRNA expression in the hypothalamus and spleen, and the period of expression increase paralleled the onset period of anorexia. In addition, pretreatment with JNJ7777120 completely inhibited the increased expression. These results suggest that TNF-α mRNA expression via H 4 receptors may contribute to the development of cisplatin-induced anorexia, and that H 4 receptor antagonists are potentially useful treatments. Copyright © 2018 Elsevier B.V. All rights reserved.

Regional Differential Effects of the Novel Histamine H3 Receptor Antagonist 6-[(3-Cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-N-methyl-3-pyridinecarboxamide hydrochloride (GSK189254) on Histamine Release in the Central Nervous System of Freely Moving Rats

OpenAIRE

Giannoni, Patrizia; Medhurst, Andrew D.; Passani, Maria Beatrice; Giovannini, Maria Grazia; Ballini, Chiara; Corte, Laura Della; Blandina, Patrizio

2010-01-01

After oral administration, the nonimidazole histamine H3 receptor antagonist, 6-[(3-cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-N-methyl-3-pyridinecarboxamide hydrochloride (GSK189254), increased histamine release from the tuberomammillary nucleus, where all histaminergic somata are localized, and from where their axons project to the entire brain. To further understand functional histaminergic circuitry in the brain, dual-probe microdialysis was used to pharmacologically block H3...

The Histamine H4 Receptor: From Orphan to the Clinic

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Robin L. Thurmond

2015-03-01

Full Text Available The histamine H4 receptor (H4R was first noted as a sequence in genomic databases that had features of a G-protein coupled receptor. This putative receptor was found to bind histamine consistent with its homology to other histamine receptors and thus became the fourth member of the histamine receptor family. Due to the previous success of drugs that target the H1 and H2 receptors, an effort was made to understand the function of this receptor and determine if it represented a drug target. Taking advantage of the vast literature on histamine, a search for histamine activity that did not appear to be mediated by the other three histamine receptors was undertaken. From this asthma and pruritus emerged as areas of particular interest. Histamine has long been suspected to play a role in the pathogenesis of asthma, but antihistamines that target the H1 and H2 receptors have not been shown to be effective for this condition. The use of selective ligands in animal models of asthma has now potentially filled this gap by showing a role for the H4R in mediating lung function and inflammation. A similar story exists for chronic pruritus associated with conditions such as atopic dermatitis. Antihistamines that target the H1 receptor are effective in reducing acute pruritus, but are ineffective in pruritus experienced by patients with atopic dermatitis. As for asthma, animal models have now suggested a role for the H4R in mediating pruritic responses, with antagonists to the H4R reducing pruritus in a number of different conditions. The anti-pruritic effect of H4R antagonists has recently been shown in human clinical studies, validating the preclinical findings in the animal models. A selective H4R antagonist inhibited histamine-induced pruritus in health volunteers and reduced pruritus in patients with atopic dermatitis. The history to date of the H4R provides an excellent example of the deorphanization of a novel receptor and the translation of this into

Self-assembly of a supramolecular square between [Ni(dppe(TOF2] and 4,4'-Bipyridine

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Paulo Torres

2013-08-01

Full Text Available The main interest of this research is to contribute to the development and understanding of supramolecular chemistry and molecular architectures, which are constructed by the self-assembly of supramolecular entities. Therefore, the synthesis and characterization (IR, UV, 1H NMR, 31P, 19F, 1H-1H COSY of a nickel (II supramolecular square [7] was performed through the synthesis between nickel chloride [1] and diphenylphosphinoethane (dppe [2] to form the precursor complex [Ni(dppeCl2] [3]. This was followed by the synthesis of the complex of interest, [Ni(dppe(TOF2] [5], using the precursor and silver trifluoromethanesulfonate (Ag-TOF. Finally, the self-assembly was performed between the complex [1,2-bis(diphenylphosphinoethanebistriflatonickel(II] [Ni(dppe(OSO2CF32] [5] and the organic ligand 4,4'-bipyridine [6], which act as vertex and edge, respectively.According to various analyses, it was found that the self-assembly generated only one supramolecular species; a square is the most probable thermodynamic structure.

Effects of histamine and 5-hydroxytryptamine on the growth rate of xenografted human bronchogenic carcinomas.

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Sheehan, P F; Baker, T; Tutton, P J; Barkla, D H

1996-01-01

1. The influence of histamine and 5-hydroxytryptamine (5-HT) antagonists and agonists on the volume doubling times (Td) of human bronchogenic carcinomas propagated as s.c. xenografts in immunosuppressed mice was examined. 2. The H2-receptor antagonists, cimetidine and ranitidine, increased Td. 3. Treatment with the H2-receptor agonist, 4-methyl histamine, had no effect on Td. 4. Co-administration of 4-methyl histamine and cimetidine abolished the effects of cimetidine. 5. The 5-HT2-receptor antagonists, cinanserin and ketanserin, both increased Td. 6. Treatment with the 5-HT1/2-receptor agonist quipazine (0.1 mg/kg, reflecting 5-HT2 agonist activity) decreased Td, while a higher dose (10.0 mg/kg) had no effect. 7. The 5-HT1/2-receptor antagonist, methiothepin, decreased Td. 8. The 5-HT uptake inhibitor, fluoxetine, increased Td in one tumour line but not in another, while the 5-HT releaser/depletor, fenfluramine, increased Td. 9. Histamine may stimulate tumour growth through the histamine H2-receptor, while the dominant effect of 5-HT is 5-HT1-receptor inhibition. 10. Tumour growth in some bronchogenic carcinomas may involve 5-HT uptake mechanisms.

A new generation of anti-histamines : Histamine H4 receptor antagonists on their way to the clinic

NARCIS (Netherlands)

Engelhardt, Harald; Smits, Rogier A; Leurs, Rob; Haaksma, Eric E J; de Esch, Iwan J P

At the turn of the millennium, the DNA sequence encoding the histamine H4 receptor (H4R) was identified in data from human genome databases. Considering the clinical importance of H1R and H2R ligands, and the clinical trials that are ongoing for H3R ligands, the latest addition to the histamine

Influence of the novel histamine H₃ receptor antagonist ST1283 on voluntary alcohol consumption and ethanol-induced place preference in mice.

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Bahi, Amine; Sadek, Bassem; Schwed, Stephan J; Walter, Miriam; Stark, Holger

2013-07-01

Growing evidence supports a role for the central histaminergic system to have a modulatory influence on drug addiction in general and alcohol-use disorders in particular through histamine H3 receptors (H3R). In the present study, the effects of systemic injection of the newly synthesized H3R antagonist ST1283 on ethanol (EtOH) voluntary intake and EtOH-conditioned reward in mice have been investigated. Oral EtOH, saccharin, and quinine intake was assessed in a two-bottle choice paradigm using escalating concentrations of alcohol or tastant solutions. EtOH-induced place preference (CPP), EtOH-induced locomotor activity, and blood ethanol concentration (BEC) were also measured. Following administration of the H3R antagonist (2.5, 5, and 10 mg/kg, i.p.), there was a significant dose-dependent decrease in alcohol consumption and preference. Importantly, vehicle- and ST1283 (5 mg/kg)-treated mice showed similar consumption and preference to increasing concentration of both sweet and bitter tastes. More interestingly, systemic administration of ST1283 inhibited EtOH-CPP and EtOH-enhanced locomotion. This inhibition was blocked when mice were pretreated with the selective H3R agonist R-(alpha)-methyl-histamine (10 mg/kg). Finally, vehicle- and ST1283-treated mice had similar BECs. Our results show that ST1283 may decrease voluntary EtOH consumption and EtOH-CPP by altering its reinforcing effects, suggesting a novel role for histamine signaling in regulation of alcoholism. Lastly, the results add to the growing literature on H3R modulation in the pharmacotherapy of EtOH addiction.

Histamine Excites Rat Superior Vestibular Nuclear Neurons via Postsynaptic H1 and H2 Receptors in vitro

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Qian-Xing Zhuang

2012-09-01

Full Text Available The superior vestibular nucleus (SVN, which holds a key position in vestibulo-ocular reflexes and nystagmus, receives direct hypothalamic histaminergic innervations. By using rat brainstem slice preparations and extracellular unitary recordings, we investigated the effect of histamine on SVN neurons and the underlying receptor mechanisms. Bath application of histamine evoked an excitatory response of the SVN neurons, which was not blocked by the low-Ca2+/high-Mg2+ medium, indicating a direct postsynaptic effect of the amine. Selective histamine H1 receptor agonist 2-pyridylethylamine and H2 receptor agonist dimaprit, rather than VUF8430, a selective H4 receptor agonist, mimicked the excitation of histamine on SVN neurons. In addition, selective H1 receptor antagonist mepyramine and H2 receptor antagonist ranitidine, but not JNJ7777120, a selective H4 receptor antagonist, partially blocked the excitatory response of SVN neurons to histamine. Moreover, mepyramine together with ranitidine nearly totally blocked the histamine-induced excitation. Immunostainings further showed that histamine H1 and H2 instead of H4 receptors existed in the SVN. These results demonstrate that histamine excites the SVN neurons via postsynaptic histamine H1 and H2 receptors, and suggest that the central histaminergic innervation from the hypothalamus may actively bias the SVN neuronal activity and subsequently modulate the SVN-mediated vestibular functions and gaze control.

Structure-Based Prediction of Subtype Selectivity of Histamine H3 Receptor Selective Antagonists in Clinical Trials

DEFF Research Database (Denmark)

Kim, Soo-Kyung; Fristrup, Peter; Abrol, Ravinder

2011-01-01

applications, including treatment of Alzheimer’s disease, attention deficit hyperactivity disorder (ADHD), epilepsy, and obesity.(1) However, many of these drug candidates cause undesired side effects through the cross-reactivity with other histamine receptor subtypes. In order to develop improved selectivity...... and antagonists. We find that E2065.46 contributes most in binding H3 selective agonists (5, 6, 7) in agreement with experimental mutation studies. We also find that conserved E5.46/S5.43 in both of hH3HR and hH4HR are involved in H3/ H4 subtype selectivity. In addition, we find that M3786.55 in hH3HR provides...... additional hydrophobic interactions different from hH4HR (the corresponding amino acid of T3236.55 in hH4HR) to provide additional subtype bias. From these studies, we developed a pharmacophore model based on our predictions for known hH3HR selective antagonists in clinical study [ABT-239 1, GSK-189,254 2...

Syntheses of radiolabelled forms of a novel histamine H1 antagonist (SKandF 94944)

International Nuclear Information System (INIS)

Cashyap, M.M.; Mitchell, M.B.; Osborne, D.C.; Saunders, D.

1985-01-01

A novel histamine H 1 antagonist SKandF 93944, 2-[4-(5-bromo-3-methylpyrid-2-yl)butylamino]-5-(6-methylpyrid-3-yl-methyl)-4(3H)-pyrimidone, has been labelled with carbon-14 in two different positions for use in metabolism and pharmacokinetic studies. The four stage synthesis of [pyrimidone-2- 14 C] SKandF 93944 from barium [ 14 C]cyanamide is described. The overall radiochemical yield was 38%. [butylamino-4- 14 C] SKandF 93944 was synthesised in four steps from [ 14 C]methyl iodide. The key steps in this synthesis were alkylation of 2-lithio-3-methyl pyridine with [ 14 C]methyl iodide and the bromination of 4-(3-methyl-2-pyridyl)[4- 14 C]butylamine in a liquid sulphur trioxide/freon mixture. The overall radiochemical yield was 1.6% from [ 14 C]methyl iodide. (author)

The modulatory role of spinally located histamine receptors in the regulation of the blood glucose level in d-glucose-fed mice.

Science.gov (United States)

Sim, Yun-Beom; Park, Soo-Hyun; Kim, Sung-Su; Kim, Chea-Ha; Kim, Su-Jin; Lim, Su-Min; Jung, Jun-Sub; Ryu, Ohk-Hyun; Choi, Moon-Gi; Suh, Hong-Won

2014-02-01

The possible roles of spinal histamine receptors in the regulation of the blood glucose level were studied in ICR mice. Mice were intrathecally (i.t.) treated with histamine 1 (H1) receptor agonist (2-pyridylethylamine) or antagonist (cetirizine), histamine 2 (H2) receptor agonist (dimaprit) or antagonist (ranitidine), histamine 3 (H3) receptor agonist (α-methylhistamine) or antagonist (carcinine) and histamine 4 (H4) receptor agonist (VUF 8430) or antagonist (JNJ 7777120), and the blood glucose level was measured at 30, 60 and 120 min after i.t. administration. The i.t. injection with α-methylhistamine, but not carcinine slightly caused an elevation of the blood glucose level. In addition, histamine H1, H2, and H4 receptor agonists and antagonists did not affect the blood glucose level. In D-glucose-fed model, i.t. pretreatment with cetirizine enhanced the blood glucose level, whereas 2-pyridylethylamine did not affect. The i.t. pretreatment with dimaprit, but not ranitidine, enhanced the blood glucose level in D-glucose-fed model. In addition, α-methylhistamine, but not carcinine, slightly but significantly enhanced the blood glucose level D-glucose-fed model. Finally, i.t. pretreatment with JNJ 7777120, but not VUF 8430, slightly but significantly increased the blood glucose level. Although histamine receptors themselves located at the spinal cord do not exert any effect on the regulation of the blood glucose level, our results suggest that the activation of spinal histamine H2 receptors and the blockade of spinal histamine H1 or H3 receptors may play modulatory roles for up-regulation and down-regulation, respectively, of the blood glucose level in D-glucose fed model.

Characteristics in Molecular Vibrational Frequency Patterns between Agonists and Antagonists of Histamine Receptors

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S. June Oh

2012-06-01

Full Text Available To learn the differences between the structure-activity relationship and molecular vibration-activity relationship in the ligand-receptor interaction of the histamine receptor, 47 ligands of the histamine receptor were analyzed by structural similarity and molecular vibrational frequency patterns. The radial tree that was produced by clustering analysis of molecular vibrational frequency patterns shows its potential for the functional classification of histamine receptor ligands.

Radioprotective effects of histamine H2 receptor antagonists famotidine and ranitidine on gamma ray induced chromosome damage

International Nuclear Information System (INIS)

Sharma, N.K.

2013-01-01

Histamine H2 receptor antagonist such as Cimetidine, Famotidine and Ranitidine are used in the clinical treatment of peptic ulcer. In vitro metaphase analysis and micronucleus assay were used to test the effects of famotidine and ranitidine on Cobalt 60 γ-ray induced clastogenic effects. Heparinised whole blood was obtained from healthy non-smoker volunteers. Blood samples were irradiated at a dose of 3Gy and incubated at 37 deg C for 1h. Lymphocyte cultures were initiated for metaphase chromosomes and cytochalasin B blocked micronucleus analysis. Aqueous solution of Famotidine (150 g/ml) and Ranitidine (500 g/ml) was added to the whole blood cultures at 0h and 24h. Cultures were harvested and processed at 48h and 72h for chromosome aberrations and micronucleus analysis respectively. Cultures treated with Famotidine at 0h and 24h after 3Gy γ-ray irradiation induce 60.90% and 56.52% inhibition in dicentrics, 48.70% and 43.61% inhibition in total aberrations. Ranitidine at 0h and 24h after 3Gy γ-ray irradiation induce 52.17% and 43.47% inhibition in dicentrics, 33.60% and 46.15% inhibition in total aberrations, when compared with 3Gy γ-ray irradiation alone. 43-54% inhibition in Binucleated cells with micronuclei and 47.72% inhibition in micronuclei at 0h treatment respectively. In conclusion radioprotective effects of Histamine H2 receptor antagonists famotidine and ranitidine on γ-ray induced chromosome damage is observed and the drugs effectively reduced the frequency of radiation induced chromosome aberrations and micronucleus. Famotidine was found to be more effective. The mechanism in which these drugs reduce clastogenic effect of γ-radiation is not fully understood. It might be due to their antioxidant and free radical-scavenging properties. (author)

The novel non-imidazole histamine H3 receptor antagonist DL77 reduces voluntary alcohol intake and ethanol-induced conditioned place preference in mice.

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Bahi, Amine; Sadek, Bassem; Nurulain, Syed M; Łażewska, Dorota; Kieć-Kononowicz, Katarzyna

2015-11-01

It has become clear that histamine H3 receptors (H3R) have been implicated in modulating ethanol intake and preference in laboratory animals. The novel non-imidazole H3R antagonist DL77 with excellent selectivity profile shows high in-vivo potency as well as in-vitro antagonist affinity with ED50 of 2.1 ± 0.2 mg/kg and pKi=8.08, respectively. In the present study, and applying an unlimited access two-bottle choice procedure, the anti-alcohol effects of the H3R antagonist, DL77 (0, 3, 10 and 30 mg/kg; i.p.), were investigated in adult mice. In this C57BL/6 line, effects of DL77 on voluntary alcohol intake and preference, as well as on total fluid intake were evaluated. Results have shown that DL77, dose-dependently, reduced both ethanol intake and preference. These effects were very selective as both saccharin and quinine, used to control for taste sensitivity, and intakes were not affected following DL77 pre-application. More importantly, systemic administration of DL77 (10 mg/kg) during acquisition inhibited ethanol-induced conditioned-place preference (EtOH-CPP) as measured using an unbiased protocol. The anti-alcohol activity observed for DL77 was abrogated when mice were pretreated with the selective H3R agonist R-(α)-methyl-histamine (RAMH) (10 mg/kg), or with the CNS penetrant H1R antagonist pyrilamine (PYR) (10mg/kg). These results suggest that DL77 has a predominant role in two in vivo effects of ethanol. Therefore, signaling via H3R is essential for ethanol-related consumption and conditioned reward and may represent a novel therapeutic pharmacological target to tackle ethanol abuse and alcoholism. Copyright © 2015 Elsevier Inc. All rights reserved.

Time-dependent histamine release from stored human blood products

DEFF Research Database (Denmark)

Nielsen, Hans Jørgen; Edvardsen, L; Vangsgaard, K

1996-01-01

storage. Whole blood (six units), plasma-reduced whole blood (six units), and plasma- and buffy coat-reduced (saline-adenine-glucose-mannitol) (SAGM) blood (six units) from unpaid healthy donors were stored in the blood bank for 35 days at 4 degrees C. Plasma histamine and total cell-bound histamine......Perioperative transfusion of whole blood has been shown to amplify trauma-induced immunosuppression, which could be attenuated by perioperative administration of histamine2 receptor antagonists. Supernatants from different blood products were, therefore, analysed for histamine content during.......0 (range 176.0-910.0) nmol/l in whole blood and 475.0 (range 360.0-1560.0) nmol/l in plasma-reduced whole blood, while it was undetectable in SAGM blood. Spontaneous histamine release increased in a time-dependent manner from a median of 6.7 (range 2.2-17.4) nmol/l at the time of storage to 175.0 (range 33...

Non-imidazole-based histamine H3 receptor antagonists with anticonvulsant activity in different seizure models in male adult rats

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Sadek B

2016-11-01

Full Text Available Bassem Sadek,1 Ali Saad,1 Gniewomir Latacz,2 Kamil Kuder,2 Agnieszka Olejarz,2 Tadeusz Karcz,2 Holger Stark,3 Katarzyna Kieć-Kononowicz2 1Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates; 2Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland; 3Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmaceutical and Medicinal Chemistry, Heinrich Heine University, Düsseldorf, Germany Abstract: A series of twelve novel non-imidazole-based ligands (3–14 was developed and evaluated for its in vitro binding properties at the human histamine H3 receptor (hH3R. The novel ligands were investigated for their in vivo protective effects in different seizure models in male adult rats. Among the H3R ligands (3–14 tested, ligand 14 showed significant and dose-dependent reduction in the duration of tonic hind limb extension in maximal electroshock (MES-induced seizure model subsequent to acute systemic administration (5, 10, and 20 mg/kg, intraperitoneally, whereas ligands 4, 6, and 7 without appreciable protection in MES model were most promising in pentylenetetrazole (PTZ model. Moreover, the protective effect observed for ligand 14 in MES model was lower than that observed for the reference drug phenytoin and was entirely abrogated when rats were co-administered with the brain-penetrant H1R antagonist pyrilamine (PYR but not the brain-penetrant H2R antagonist zolantidine (ZOL, demonstrating that histaminergic neurotransmission by activation of postsynaptically located H1Rs seems to be involved in the protective action. On the contrary, PYR and ZOL failed to abrogate the full protection provided by 4 in PTZ model and the moderate protective effect by 14 in strychnine (STR model. Moreover, the experimental and in silico estimation of properties such as metabolism was

Regional differential effects of the novel histamine H3 receptor antagonist 6-[(3-cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-N-methyl-3-pyridinecarboxamide hydrochloride (GSK189254) on histamine release in the central nervous system of freely moving rats.

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Giannoni, Patrizia; Medhurst, Andrew D; Passani, Maria Beatrice; Giovannini, Maria Grazia; Ballini, Chiara; Corte, Laura Della; Blandina, Patrizio

2010-01-01

After oral administration, the nonimidazole histamine H(3) receptor antagonist, 6-[(3-cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-N-methyl-3-pyridinecarboxamide hydrochloride (GSK189254), increased histamine release from the tuberomammillary nucleus, where all histaminergic somata are localized, and from where their axons project to the entire brain. To further understand functional histaminergic circuitry in the brain, dual-probe microdialysis was used to pharmacologically block H(3) receptors in the tuberomammillary nucleus, and monitor histamine release in projection areas. Perfusion of the tuberomammillary nucleus with GSK189254 increased histamine release from the tuberomammillary nucleus, nucleus basalis magnocellularis, and cortex, but not from the striatum or nucleus accumbens. Cortical acetylcholine (ACh) release was also increased, but striatal dopamine release was not affected. When administered locally, GSK189254 increased histamine release from the nucleus basalis magnocellularis, but not from the striatum. Thus, defined by their sensitivity to GSK189254, histaminergic neurons establish distinct pathways according to their terminal projections, and can differentially modulate neurotransmitter release in a brain region-specific manner. Consistent with its effects on cortical ACh release, systemic administration of GSK189254 antagonized the amnesic effects of scopolamine in the rat object recognition test, a cognition paradigm with important cortical components.

Brain histamine depletion enhances the behavioural sequences complexity of mice tested in the open-field: Partial reversal effect of the dopamine D2/D3 antagonist sulpiride.

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Santangelo, Andrea; Provensi, Gustavo; Costa, Alessia; Blandina, Patrizio; Ricca, Valdo; Crescimanno, Giuseppe; Casarrubea, Maurizio; Passani, M Beatrice

2017-02-01

Markers of histaminergic dysregulation were found in several neuropsychiatric disorders characterized by repetitive behaviours, thoughts and stereotypies. We analysed the effect of acute histamine depletion by means of i. c.v. injections of alpha-fluoromethylhistidine, a blocker of histidine decarboxylase, on the temporal organization of motor sequences of CD1 mice behaviour in the open-field test. An ethogram encompassing 9 behavioural components was employed. Durations and frequencies were only slightly affected by treatments. However, as revealed by multivariate t-pattern analysis, histamine depletion was associated with a striking increase in the number of behavioural patterns. We found 42 patterns of different composition occurring, on average, 520.90 ± 50.23 times per mouse in the histamine depleted (HD) group, whereas controls showed 12 different patterns occurring on average 223.30 ± 20.64 times. Exploratory and grooming behaviours clustered separately, and the increased pattern complexity involved exclusively exploratory patterns. To test the hypothesis of a histamine-dopamine interplay on behavioural pattern phenotype, non-sedative doses of the D2/D3 antagonist sulpiride (12.5-25-50 mg/kg) were additionally administered to different groups of HD mice. Sulpiride counterbalanced the enhancement of exploratory patterns of different composition, but it did not affect the mean number of patterns at none of the doses used. Our results provide new insights on the role of histamine on repetitive behavioural sequences of freely moving mice. Histamine deficiency is correlated with a general enhancement of pattern complexity. This study supports a putative involvement of histamine in the pathophysiology of tics and related disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Influence of histamine H1-receptor on liver functions in immunized rabbits.

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Tripathi, Trivendra; Shahid, Mohammad; Khan, Haris M; Khan, Rahat Ali; Siddiqui, Mashiatullah; Mahdi, Abbas Ali

2011-10-01

This study was designed to investigate the functional roles of histamine and histamine H1-receptor agonist and antagonist in the development of liver function impairment in immunized rabbits. The study comprised of six groups containing 18 rabbits each. Group III-VI received histamine (100 μg/kg, s.c.), H1R-agonist (HTMT, 10 μg/kg, s.c.), H1R-antagonist (pheniramine, 10 mg/kg, i.m.), and H1R-antagonist (pheniramine, 10 mg/kg, i.m.) plus histamine (100 μg/kg, s.c.), respectively, b.i.d. for 10 days. Group I (negative control) and group II (positive control) received sterile distilled water intramuscularly b.i.d. for 10 days. Groups II-VI were immunized on day 3 with intravenous injection of SRBC (1 × 10(9) cells/ml). Blood samples were collected on pre-immunization day 0, as well as on days 7-, 14-, 21-, 28-, and 58-post-immunization. Biochemical parameters AST, ALT, alkaline phosphatase and bilirubin [total bilirubin (TB), direct bilirubin (DB), and indirect bilirubin (IB)] were determined. On each experimental day, the mean values of serum enzymes and bilirubin in group I and group II showed no significant changes while in group III, IV, V, and VI, these enzymes and bilirubin levels showed significant changes (p pheniramine, and combination of histamine + pheniramine cause hepatic function impairment in terms of altered serum enzymes and bilirubin levels. The present findings suggest that HTMT causes moderate liver function impairment while others show mild impairment.

Histamine ameliorates spatial memory deficits induced by MK-801 infusion into ventral hippocampus as evaluated by radial maze task in rats

Institute of Scientific and Technical Information of China (English)

Li-sha XU; Li-xia YANG; Wei-wei HU; Xiao YU; Li MA; Lu-ying LIU; Er-qing WEI; Zhong CHEN

2005-01-01

Aim: To investigate the role of histamine in memory deficits induced by MK-801 infusion into the ventral hippocampus in rats. Methods: An 8-arm radial maze (4arms baited) was used to assess spatial memory. Results: Bilateral ventral intrahippocampal (ih) infusion of MK-801 (0.3 μg/site), an N-methyl-D-aspartate (NMDA) antagonist, impaired the retrieval process in both working memory and reference memory. Intrahippocampal injection of histamine (25 or 50 ng/site) or intraperitoneal (ip) injection of histidine (25, 50 or 100 mg/kg) markedly ameliorated the spatial memory deficits induced by MK-801. Both the histamine H1 antagonist pyrilamine (0.5 or 1.0 μg/site, ih) and the H2 antagonist cimetidine (2.5 μg/site,ih) abolished the ameliorating effect of histidine (100 mg/kg, ip) on reference memory deficits, but not that on working memory deficits induced by MK-801. Conclusion:The results indicate that histamine in the ventral hippocampus can ameliorate MK-801-induced spatial memory deficits, and that histamine's effect on reference memory is mediated by postsynaptic histamine H1 and H2 receptors.

A CD1d-dependent lipid antagonist to NKT cells ameliorates atherosclerosis in ApoE-/- mice by reducing lesion necrosis and inflammation.

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Li, Yi; Kanellakis, Peter; Hosseini, Hamid; Cao, Anh; Deswaerte, Virginie; Tipping, Peter; Toh, Ban-Hock; Bobik, Alex; Kyaw, Tin

2016-02-01

Atherosclerosis-related deaths from heart attacks and strokes remain leading causes of global mortality, despite the use of lipid-lowering statins. Thus, there is an urgent need to develop additional therapies. Reports that NKT cells promote atherosclerosis and an NKT cell CD1d-dependent lipid antagonist (DPPE-PEG350, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N[methoxy(polyethyleneglycol)-350]) reduces allergen-induced inflammation led us to investigate its therapeutic potential in preventing the development and progression of experimental atherosclerosis. DPPE-PEG350 was administered to hyperlipidaemic ApoE(-/-) mice with/without established atherosclerosis. Atherosclerosis and immune cells were assessed in the aortic sinus lesions. Lesion expression of monocyte chemoattractant protein-1 (MCP-1) and vascular cell adhesion protein-1 (VCAM-1) responsible for inflammatory immune cell recruitment as well as mRNA expression of IFNγ and its plasma levels were investigated. Necrotic cores and lesion smooth muscle and collagen contents important in plaque stability were determined as were plasma lipid levels. DPPE-PEG350 reduced atherosclerosis development and delayed progression of established atherosclerosis without affecting plasma lipids. CD4 and CD8 T cells and B cells in atherosclerotic lesions were decreased in DPPE-PEG350-treated mice. Lesion MCP-1 and VCAM-1 protein expression and necrotic core size were reduced without affecting lesion smooth muscle and collagen content. IFNγ and lymphocytes were unaffected by the treatment. The attenuation of progression of established atherosclerosis together with reduced development of atherosclerosis in hyperlipidaemic mice by the NKT antagonist, without affecting NKT cell or other lymphocyte numbers, suggests that targeting lesion inflammation via CD1d-dependent activation of NKT cells using DPPE-PEG350 has a therapeutic potential in treating atherosclerosis. Published on behalf of the European Society of

Receptor-independent, vacuolar ATPase-mediated cellular uptake of histamine receptor-1 ligands: Possible origin of pharmacological distortions and side effects

International Nuclear Information System (INIS)

Morissette, Guillaume; Lodge, Robert; Bouthillier, Johanne; Marceau, Francois

2008-01-01

The aims of this study were to investigate whether several histamine receptor agonists and antagonists are subjected to receptor-independent ion trapping into acidic organelles, and whether this sequestration influences their pharmacological or toxicological properties. Vacuolar (V)-ATPase-dependent intracellular sequestration of agonists was recognized as morphological alterations (large fluid-filled vacuoles for betahistine and 1-methylhistamine, granular uptake for fluorescent BODIPY FL histamine) prevented by the specific V-ATPase inhibitor bafilomycin A1 in rabbit vascular smooth muscle cells. Lipophilicity was the major determinant of these cellular effects (order of potency: BODIPY FL histamine > betahistine > 1-methylhistamine > histamine) that occurred at high concentrations. This ranking was dissociable from the potency order for H 1 receptor-mediated contraction of the rabbit aorta, a response uninfluenced by bafilomycin. Antihistamines are inherently more lipophilic and caused vacuolization of a proportion of cells at 5-500 μM. Agonist or antagonist-induced vacuoles were of macroautophagic nature (labeled with GFP-conjugated LC3, Rab7 and CD63; detection of LC3 II). Further, the 2 most lipophilic antihistamines tested, astemizole and terfenadine, were potentiated by V-ATPase blockade in the aortic contractility assay (13- and 3.6-fold more potent, respectively, pA 2 scale), suggesting that V-ATPase-mediated cation trapping sequesters these antagonists from the vicinity of H 1 receptors in the therapeutic concentration range. This potentiation did not apply to less lipophilic antagonists (pyrilamine, diphenhydramine). While some agonists and all tested antagonists of the histamine H 1 receptors induce the V-ATPase-dependent vacuolar and autophagic cytopathology, sequestration affects the pharmacology of only the most lipophilic antagonists, the ones prone to off-target arrhythmogenic side effects

Mixed-ligand complexes of technetium-III. Synthesis and characterization of [bis(diphenylphosphino)ethane]tetrakis(trimethylphosphite)tech netium(I) hexafluorophosphate, [Tc(DPPE)(TMP)4]PF6

International Nuclear Information System (INIS)

Abram, U.; Beyer, R.; Muenze, R.; Stach, J.; Kaden, L.; Lorenz, B.; Findeisen, M.

1989-01-01

The diamagnetic technetium(I) complex [Tc(DPPE)(TMP) 4 ]PF 6 was prepared from [Tc(N 2 )H(DPPE) 2 ] and characterized by elemental analysis. 1 H- and 99 Tc-NMR spectroscopy and fast atom bombardment mass spectrometry. [Tc(DPPE)(TMP) 4 ]PF 6 is a prototype compound for technetium complexes with mixed phosphine-phosphite coordination spheres. (author)

The effect of betahistine, a histamine H1 receptor agonist/H3 antagonist, on olanzapine-induced weight gain in first-episode schizophrenia patients.

Science.gov (United States)

Poyurovsky, Michael; Pashinian, Artashes; Levi, Aya; Weizman, Ronit; Weizman, Abraham

2005-03-01

Histamine antagonism has been implicated in antipsychotic drug-induced weight gain. Betahistine, a histamine enhancer with H1 agonistic/H3 antagonistic properties (48 mg t.i.d.), was coadministered with olanzapine (10 mg/day) in three first-episode schizophrenia patients for 6 weeks. Body weight was measured at baseline and weekly thereafter. Clinical rating scales were completed at baseline and at week 6. All participants gained weight (mean weight gain 3.1+/-0.9 kg) and a similar pattern of weight gain was observed: an increase during the first 2 weeks and no additional weight gain (two patients) or minor weight loss (one patient) from weeks 3 to 6. None gained 7% of baseline weight, which is the cut-off for clinically significant weight gain. Betahistine was safe and well tolerated and did not interfere with the antipsychotic effect of olanzapine. Our findings justify a placebo-controlled evaluation of the putative weight-attenuating effect of betahistine in olanzapine-induced weight gain.

The dual orexin receptor antagonist, DORA-22, lowers histamine levels in the lateral hypothalamus and prefrontal cortex without lowering hippocampal acetylcholine.

Science.gov (United States)

Yao, Lihang; Ramirez, Andres D; Roecker, Anthony J; Fox, Steven V; Uslaner, Jason M; Smith, Sean M; Hodgson, Robert; Coleman, Paul J; Renger, John J; Winrow, Christopher J; Gotter, Anthony L

2017-07-01

Chronic insomnia is defined as a persistent difficulty with sleep initiation maintenance or non-restorative sleep. The therapeutic standard of care for this condition is treatment with gamma-aminobutyric acid (GABA) A receptor modulators, which promote sleep but are associated with a panoply of side effects, including cognitive and memory impairment. Dual orexin receptor antagonists (DORAs) have recently emerged as an alternative therapeutic approach that acts via a distinct and more selective wake-attenuating mechanism with the potential to be associated with milder side effects. Given their distinct mechanism of action, the current work tested the hypothesis that DORAs and GABA A receptor modulators differentially regulate neurochemical pathways associated with differences in sleep architecture and cognitive performance induced by these pharmacological mechanisms. Our findings showed that DORA-22 suppresses the release of the wake neurotransmitter histamine in the lateral hypothalamus, prefrontal cortex, and hippocampus with no significant alterations in acetylcholine levels. In contrast, eszopiclone, commonly used as a GABA A modulator, inhibited acetylcholine secretion across brain regions with variable effects on histamine release depending on the extent of wakefulness induction. In normal waking rats, eszopiclone only transiently suppressed histamine secretion, whereas this suppression was more obvious under caffeine-induced wakefulness. Compared with the GABA A modulator eszopiclone, DORA-22 elicits a neurotransmitter profile consistent with wake reduction that does not impinge on neurotransmitter levels associated with cognition and rapid eye movement sleep. © 2017 International Society for Neurochemistry.

Activation of Microglia by Histamine and Substance P

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Jin Zhu

2014-08-01

Full Text Available Background: Activated microglia perform many of the immune effector functions typically associated with macrophages. However, the regulators involved in microglial activation are not well defined. Because microglia play a pivotal role in immune surveillance of the CNS, we studied the effect of the neuromediators histamine and substance P on microglia. Methods: The induction of microglial activation by histamine and substance P was examined using primary cultured microglia. Fluorescent images were acquired with a confocal microscope. The levels of TNF-α and IL-6 were measured with a commercial ELISA kit. Intracellular reactive oxygen species (ROS levels were determined by dichlorodihydrofluorescein oxidation. The mitochondrial membrane potential was assessed with the MitoProbe™ JC-1 assay kit. Results: We found that the neuromediators histamine and substance P were able to stimulate microglial activation and the subsequent production of ROS and proinflammatory factors TNF-α and IL-6. These effects were partially abolished by antagonists of the histamine receptors H1 and H4 and of the substance P receptors NK-1, NK-2 and NK-3. Histamine induced mitochondrial membrane depolarization in microglia. Conclusions: These results indicate that the neuromediators histamine and SP can trigger microglial activation and release of pro-inflammatory factors from microglia, thus contributing to the development of microglia-mediated inflammation in the brain.

On the role of serotonin and histamine in neurohumoral mechanisms of postirradiation diarrhea in rats

International Nuclear Information System (INIS)

Legeza, V.I.; Shagoyan, M.G.; Markovskaya, I.V.; Vasil'eva, T.P.; Pozharisskaya, T.D.; Alekseeva, I.I.; Lokteva, O.I.

1990-01-01

In experiments with rats exposed to 200 Gy radiation it was shown that the diarrhea effect of serotonin under the effect of radiation is implemented via D- and M-type receptors, and that of histamine via H 1 and H 2 receptors. Serotonin and histamine, that were released under the effect of radiation from endocrine and mast cells of the digestive tract stimulated the propulsion activity of the intestine whereas histamine, in addition, inhibited the absorption process. It is suggested that serotonin and histamine antagonists should be used as means of preventing of radiation-induced diarrhea

Histamine receptors in human detrusor smooth muscle cells: physiological properties and immunohistochemical representation of subtypes.

Science.gov (United States)

Neuhaus, Jochen; Weimann, Annett; Stolzenburg, Jens-Uwe; Dawood, Waled; Schwalenberg, Thilo; Dorschner, Wolfgang

2006-06-01

The potent inflammatory mediator histamine is released from activated mast cells in interstitial cystitis (IC). Here, we report on the histamine receptor subtypes involved in the intracellular calcium response of cultured smooth muscle cells (cSMC). Fura-2 was used to monitor the calcium response in cSMC, cultured from human detrusor biopsies. The distribution of histamine receptor subtypes was addressed by immunocytochemistry in situ and in vitro. Histamine stimulated a maximum of 92% of the cells (n=335), being more effective than carbachol (70%, n=920). HTMT (H1R-agonist), dimaprit (H2R) and MTH (H3R) lead to significant lower numbers of reacting cells (60, 48 and 54%). Histamine receptor immunoreactivity (H1R, H2R, H3R, H4R) was found in situ and in vitro. Histamine-induced calcium increase is mediated by distinct histamine receptors. Thus, pre-therapeutic evaluation of histamine receptor expression in IC patients may help to optimize therapy by using a patient-specific cocktail of subtype-specific histamine receptor antagonists.

Histamine and tryptase in nasal lavage fluid after allergen challenge

DEFF Research Database (Denmark)

Jacobi, H H; Skov, P S; Poulsen, L K

1999-01-01

BACKGROUND: Antihistamines (H1-receptor antagonists) act by competitive antagonism of histamine at H1-receptors. In addition, high concentrations of some antihistamines inhibit allergen-induced histamine release from mast cells in vitro. OBJECTIVE: The purpose of this study was to determine...... the effect of intranasal azelastine or systemic cetirizine (both potent antihistamines) on the allergen-induced release of mast-cell mediators from the human nasal mucosa in vivo. METHODS: Patients allergic to birch pollen (n = 11) and control subjects not allergic to birch pollen (n = 5) were included......, nasal allergen challenges were performed, and the number of sneezes were counted. In addition, nasal lavage fluid was collected, and the levels of mast-cell mediators (histamine and tryptase) were measured. RESULTS: The allergen challenge of patients allergic to pollen produced sneezing...

Histamine response and local cooling in the human skin: involvement of H1- and H2-receptors.

Science.gov (United States)

Grossmann, M; Jamieson, M J; Kirch, W

1999-08-01

Histamine may contribute locally to cutaneous blood flow control under normal and pathologic conditions. The objective of this study was to observe the influence of skin temperature on histamine vasodilation, and the roles of H1-and H2-receptors using novel noninvasive methods. Eleven healthy subjects received, double-blind, single doses of the H1-receptor antagonist cetirizine (10 mg), cetirizine (10 mg) plus the H2-receptor antagonist cimetidine (400 mg), or placebo on separate occasions. Histamine was dosed cumulatively by iontophoresis to the forearm skin at 34 degrees C and 14 degrees C. Laser-Doppler flux (LDF) was measured at the same sites using customised probeholder/iontophoretic chambers with Peltier cooling elements. Finger mean arterial pressure (MAP) was measured and cutaneous vascular conductance calculated as LDF/MAP. Histamine vasodilation was reduced in cold skin. Cetirizine shifted the histamine dose-response at both temperatures: statistically significantly at 14 degrees C only. Combined H1- and H2-receptor antagonism shifted the response significantly at both temperatures. H1- and H2-receptors mediate histamine-induced skin vasodilation. The sensitivity of these receptors, particularly the H1- receptor, is attenuated at low skin temperature. Whether the reduced effect in cold skin represents specific receptor or postreceptor desensitization, or nonspecific attenuation of cutaneous vasodilation remains to be elucidated.

Systematic review: Antacids, H2-receptor antagonists, prokinetics, bismuth and sucralfate therapy for non-ulcer dyspepsia.

Science.gov (United States)

Moayyedi, P; Soo, S; Deeks, J; Forman, D; Harris, A; Innes, M; Delaney, B

2003-05-15

Evidence for the effectiveness of antacids, histamine-2 receptor antagonists, bismuth salts, sucralfate and prokinetic therapy in non-ulcer dyspepsia is conflicting. To conduct a systematic review evaluating these therapies in non-ulcer dyspepsia. Electronic searches were performed using the Cochrane Controlled Trials Register, Medline, EMBASE, Cinahl and SIGLE until September 2002. Dyspepsia outcomes were dichotomized into cured/improved vs. same/worse. Prokinetics [14 trials, 1053 patients; relative risk reduction (RRR), 48%; 95% confidence interval (95% CI), 27-63%] and histamine-2 receptor antagonists (11 trials, 2164 patients; RRR, 22%; 95% CI, 7-35%) were significantly more effective than placebo. Bismuth salts (RRR, 40%; 95% CI, - 3% to 65%) were superior to placebo, but this was of marginal statistical significance. Antacids and sucralfate were not statistically significantly superior to placebo. A funnel plot suggested that the prokinetic and histamine-2 receptor antagonist results could be due to publication bias. The meta-analyses suggest that histamine-2 receptor antagonists and prokinetics are superior to placebo. These data are difficult to interpret, however, as funnel plot asymmetry suggests that the magnitude of the effect could be due to publication bias or other heterogeneity-related issues.

Modulation of Mast Cell Toll-Like Receptor 3 Expression and Cytokines Release by Histamine

Directory of Open Access Journals (Sweden)

Guogang Xie

2018-05-01

Full Text Available Background/Aims: As a major inflammatory molecule released from mast cell activation, histamine has been reported to regulate TLRs expression and cytokine production in inflammatory cells present in the microenvironment. In this study, we determined the ability of histamine to modulate TLRs expression and cytokine production in mast cells. Methods: HMC-1 and P815 cells were exposed to various concentrations of histamine in the presence or absence of histamine antagonist for 2, 6 or 16 h. The effect of histamine on the expression of TLR3 protein and mRNA was analyzed by flow cytometry、 RT-PCR and immunofluorescent microscopy. Furthermore, we also examined the effect of histamine on the secretion of MCP-1 and IL-13 from mast cells by ELISA. Results: The amplification of TLR3 mRNA and protein expression in mast cells was observed after incubation with histamine, which was accompanied by increasing secretion of IL-13 and MCP-1 via H1 receptor. The signaling pathways of PI3K/ Akt and Erk1/2/MAPK contributed to these induction effects. Conclusion: These results demonstrate that histamine up-regulates the expression of TLR3 and secretion of IL-13 and MCP-1 in mast cells, thus identifying a new mechanism for the histamine inducing allergic response.

Effects of the histamine H₃ receptor antagonist ABT-239 on cognition and nicotine-induced memory enhancement in mice.

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Kruk, Marta; Miszkiel, Joanna; McCreary, Andrew C; Przegaliński, Edmund; Filip, Małgorzata; Biała, Grażyna

2012-01-01

The strong correlation between central histaminergic and cholinergic pathways on cognitive processes has been reported extensively. However, the role of histamine H(3) receptor mechanisms interacting with nicotinic mechanisms has not previously been extensively investigated. The current study was conducted to determine the interactions of nicotinic and histamine H(3) receptor systems with regard to learning and memory function using a modified elevated plus-maze test in mice. In this test, the latency for mice to move from the open arm to the enclosed arm (i.e., transfer latency) was used as an index of memory. We tested whether ABT-239 (4-(2-{2-[(2R)-2-methylpyrrolidinyl]ethyl}-benzofuran-5-yl), an H(3) receptor antagonist/inverse agonist, had influence on two different stages of memory, i.e., memory acquisition and consolidation (administered prior to or immediately after the first trial, respectively) and whether ABT-239 influenced nicotine-induced memory enhancement. Our results revealed that the acute administration of nicotine (0.035 and 0.175 mg/kg), but not of ABT-239 (0.1-3 mg/kg) reduced transfer latency in the acquisition and consolidation phases. In combination studies, concomitant administration of either ABT-239 (1 and 3 mg/kg) and nicotine (0.035 mg/kg), or ABT-239 (0.1 mg/kg) and nicotine (0.0175 mg/kg) further increased nicotine-induced improvement in both memory acquisition and consolidation. The present data confirm an important role for H(3) receptors in regulating nicotine-induced mnemonic effects since inhibition of H(3) receptors augmented nicotine-induced memory enhancement in mice.

TRPV1 and PLC Participate in Histamine H4 Receptor-Induced Itch.

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Jian, Tunyu; Yang, Niuniu; Yang, Yan; Zhu, Chan; Yuan, Xiaolin; Yu, Guang; Wang, Changming; Wang, Zhongli; Shi, Hao; Tang, Min; He, Qian; Lan, Lei; Wu, Guanyi; Tang, Zongxiang

2016-01-01

Histamine H4 receptor has been confirmed to play a role in evoking peripheral pruritus. However, the ionic and intracellular signaling mechanism of activation of H4 receptor on the dorsal root ganglion (DRG) neurons is still unknown. By using cell culture and calcium imaging, we studied the underlying mechanism of activation of H4 receptor on the DRG neuron. Immepip dihydrobromide (immepip)-a histamine H4 receptor special agonist under cutaneous injection-obviously induced itch behavior of mice. Immepip-induced scratching behavior could be blocked by TRPV1 antagonist AMG9810 and PLC pathway inhibitor U73122. Application of immepip (8.3-50 μM) could also induce a dose-dependent increase in intracellular Ca(2+) ([Ca(2+)]i) of DRG neurons. We found that 77.8% of the immepip-sensitized DRG neurons respond to the TRPV1 selective agonist capsaicin. U73122 could inhibit immepip-induced Ca(2+) responses. In addition, immepip-induced [Ca(2+)]i increase could be blocked by ruthenium red, capsazepine, and AMG9810; however it could not be blocked by TRPA1 antagonist HC-030031. These results indicate that TRPV1 but not TRPA1 is the important ion channel to induce the DRG neurons' responses in the downstream signaling pathway of histamine H4 receptor and suggest that TRPV1 may be involved in the mechanism of histamine-induced itch response by H4 receptor activation.

TRPV1 and PLC Participate in Histamine H4 Receptor-Induced Itch

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Tunyu Jian

2016-01-01

Full Text Available Histamine H4 receptor has been confirmed to play a role in evoking peripheral pruritus. However, the ionic and intracellular signaling mechanism of activation of H4 receptor on the dorsal root ganglion (DRG neurons is still unknown. By using cell culture and calcium imaging, we studied the underlying mechanism of activation of H4 receptor on the DRG neuron. Immepip dihydrobromide (immepip—a histamine H4 receptor special agonist under cutaneous injection—obviously induced itch behavior of mice. Immepip-induced scratching behavior could be blocked by TRPV1 antagonist AMG9810 and PLC pathway inhibitor U73122. Application of immepip (8.3–50 μM could also induce a dose-dependent increase in intracellular Ca2+ (Ca2+i of DRG neurons. We found that 77.8% of the immepip-sensitized DRG neurons respond to the TRPV1 selective agonist capsaicin. U73122 could inhibit immepip-induced Ca2+ responses. In addition, immepip-induced Ca2+i increase could be blocked by ruthenium red, capsazepine, and AMG9810; however it could not be blocked by TRPA1 antagonist HC-030031. These results indicate that TRPV1 but not TRPA1 is the important ion channel to induce the DRG neurons’ responses in the downstream signaling pathway of histamine H4 receptor and suggest that TRPV1 may be involved in the mechanism of histamine-induced itch response by H4 receptor activation.

Pharmacological and functional characterisation of the wild-type and site-directed mutants of the human H1 histamine receptor stably expressed in CHO cells.

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Moguilevsky, N; Varsalona, F; Guillaume, J P; Noyer, M; Gillard, M; Daliers, J; Henichart, J P; Bollen, A

1995-01-01

A cDNA clone for the human histamine H1 receptor was isolated from a lung cDNA library and stably expressed in CHO cells. The recombinant receptor protein present in the cell membranes, displayed the functional and binding characteristics of histamine H1 receptors. Mutation of Ser155 to Ala in the fourth transmembrane domain did not significantly change the affinity of the receptor for histamine and H1 antagonists. However, mutation of the fifth transmembrane Asn198 to Ala resulted in a dramatic decrease of the affinity for histamine binding, and for the histamine-induced polyphosphoinositides breakdown, whereas the affinity towards antagonists was not significantly modified. In addition, mutation of another fifth transmembrane amino acid, Thr194 to Ala also diminished, but to a lesser extent, the affinity for histamine. These data led us to propose a molecular model for histamine interaction with the human H1 receptor. In this model, the amide moiety of Asn198 and the hydroxyl group of Thr194 are involved in hydrogen bonding with the nitrogen atoms of the imidazole ring of histamine. Moreover, mutation of Thr194 to Ala demonstrated that this residue is responsible for the discrimination between enantiomers of cetirizine.

Interaction of active compounds from Aegle marmelos CORREA with histamine-1 receptor

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Nugroho, Agung Endro; Agistia, Dany Dwi; Tegar, Maulana; Purnomo, Hari

2013-01-01

The aim of this study is to determine the affinity of six active compounds of Aegle Marmelos Correa, they are (E, R)-Marmin, skimmianine, (S)-aegeline, aurapten, zeorin, and dustanin as antihistamines in histamine H1 receptor in comparison to cetirizin, diphenhydramine and chlorpheniramine as ligands comparison. Previously, in the in vitro study marmin obviously antagonized the histamine H1 receptor in a competitive manner. Methods: molecular docking to determine the interaction of ligand binding to its receptor. Lower docking score indicates more stable binding to that protein. Results: Marmin, skimmianine, aegeline, aurapten, zeorin, and dustanin were potential to develop as antihistamine agents, especially as histamine H1 receptor antagonists by interacting with amino acid residues, Asp107, Lys179, Lys191, Asn198, and Trp428 of histamine H1 receptor. Conclusions: Based on molecular docking, Amino acid residues involved in ligand protein interactions were Asp107, Lys179, Lys191, Asn198, and Trp428. PMID:23750086

UVB-induced systemic immunosuppression: role of mast cells and histamine

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Hart, P.H.; Grimbaldeston, M.A.; Finlay-Jones, J.J.

1999-01-01

Full text: UVB radiation (290-320 nm) is immunosuppressive by multiple mechanisms allowing the outgrowth of UV-induced tumours in both mouse and man. Furthermore, patients with non-melanoma skin cancers have a higher risk of death from other cancers which could be explained by UV-induced immunomodulation. The mechanism(s) of suppression by UVB depend on whether the sensitising antigen is applied to the irradiated site ('local') or to non-irradiated sites ('systemic'). In the former, the activity of UV-induced TNFα is important as it affects the migration of Langerhans cells to draining lymph nodes. In contrast, histamine from dermal mast cells is critical to the early events by which UVB can suppress systemic immune responses. The prevalence of dermal mast cells in 7 strains and substrains of mice correlates directly with their susceptibility to UVB-induced systemic immunosuppression. Furthermore, mast cell depleted mice (Wf/Wf) are resistant to UVB-induced systemic immunomodulation. However, they become susceptible after reconstitution of the site to be irradiated with bone marrow derived mast cell precursors. The mice also gain susceptibility to cis-urocanic acid-induced systemic immunomodulation. There is considerable evidence that histamine is the mast cell product critical to downstream immunosuppressive events. Firstly, physiological concentrations of histamine suppress contact hypersensitivity responses. Secondly, histamine receptor antagonists halve UVB-induced systemic immunosuppression. Thirdly, mice with different UVB-susceptibilities are equally susceptible to histamine-induced immunosuppression, and finally, histamine can suppress contact hypersensitivity responses in Wf/Wf mice. We suggest that histamine may be immunomodulatory by multiple pathways. Histamine can induce the production of immunosuppressive prostanoids from keratinocytes. A lymphocyte-derived, histamine-induced suppressor factor was reported in the 1970's. More recently histamine has

Histamine 50-skin-prick test: a tool to diagnose histamine intolerance.

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Kofler, Lukas; Ulmer, Hanno; Kofler, Heinz

2011-01-01

Background. Histamine intolerance results from an imbalance between histamine intake and degradation. In healthy persons, dietary histamine can be sufficiently metabolized by amine oxidases, whereas persons with low amine oxidase activity are at risk of histamine toxicity. Diamine oxidase (DAO) is the key enzyme in degradation. Histamine elicits a wide range of effects. Histamine intolerance displays symptoms, such as rhinitis, headache, gastrointestinal symptoms, palpitations, urticaria and pruritus. Objective. Diagnosis of histamine intolerance until now is based on case history; neither a validated questionnaire nor a routine test is available. It was the aim of this trial to evaluate the usefullness of a prick-test for the diagnosis of histamine intolerance. Methods. Prick-testing with 1% histamine solution and wheal size-measurement to assess the relation between the wheal in prick-test, read after 20 to 50 minutes, as sign of slowed histamine degradation as well as history and symptoms of histamine intolerance. Results. Besides a pretest with 17 patients with HIT we investigated 156 persons (81 with HIT, 75 controls): 64 out of 81 with histamine intolerance(HIT), but only 14 out of 75 persons from the control-group presented with a histamine wheal ≥3 mm after 50 minutes (P < .0001). Conclusion and Clinical Relevance. Histamine-50 skin-prickt-test offers a simple tool with relevance.

Calyx and dimorphic neurons of mouse Scarpa's ganglion express histamine H3 receptors

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Zucca Gianpiero

2009-06-01

Full Text Available Abstract Background Histamine-related drugs are commonly used in the treatment of vertigo and related vestibular disorders. The site of action of these drugs however has not been elucidated yet. Recent works on amphibians showed that histamine H3 receptor antagonists, e.g. betahistine, inhibit the afferent discharge recorded from the vestibular nerve. To assess the expression of H3 histamine receptors in vestibular neurons, we performed mRNA RT-PCR and immunofluorescence experiments in mouse Scarpa's ganglia. Results RT-PCR analysis showed the presence of H3 receptor mRNA in mouse ganglia tissue. H3 protein expression was found in vestibular neurons characterized by large and roundish soma, which labeled for calretinin and calbindin. Conclusion The present results are consistent with calyx and dimorphic, but not bouton, afferent vestibular neurons expressing H3 receptors. This study provides a molecular substrate for the effects of histamine-related antivertigo drugs acting on (or binding to H3 receptors, and suggest a potential target for the treatment of vestibular disorders of peripheral origin.

Calyx and dimorphic neurons of mouse Scarpa's ganglion express histamine H3 receptors.

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Tritto, Simona; Botta, Laura; Zampini, Valeria; Zucca, Gianpiero; Valli, Paolo; Masetto, Sergio

2009-06-29

Histamine-related drugs are commonly used in the treatment of vertigo and related vestibular disorders. The site of action of these drugs however has not been elucidated yet. Recent works on amphibians showed that histamine H3 receptor antagonists, e.g. betahistine, inhibit the afferent discharge recorded from the vestibular nerve. To assess the expression of H3 histamine receptors in vestibular neurons, we performed mRNA RT-PCR and immunofluorescence experiments in mouse Scarpa's ganglia. RT-PCR analysis showed the presence of H3 receptor mRNA in mouse ganglia tissue. H3 protein expression was found in vestibular neurons characterized by large and roundish soma, which labeled for calretinin and calbindin. The present results are consistent with calyx and dimorphic, but not bouton, afferent vestibular neurons expressing H3 receptors. This study provides a molecular substrate for the effects of histamine-related antivertigo drugs acting on (or binding to) H3 receptors, and suggest a potential target for the treatment of vestibular disorders of peripheral origin.

Histamine induces microglia activation and dopaminergic neuronal toxicity via H1 receptor activation.

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Rocha, Sandra M; Saraiva, Tatiana; Cristóvão, Ana C; Ferreira, Raquel; Santos, Tiago; Esteves, Marta; Saraiva, Cláudia; Je, Goun; Cortes, Luísa; Valero, Jorge; Alves, Gilberto; Klibanov, Alexander; Kim, Yoon-Seong; Bernardino, Liliana

2016-06-04

Histamine is an amine widely known as a peripheral inflammatory mediator and as a neurotransmitter in the central nervous system. Recently, it has been suggested that histamine acts as an innate modulator of microglial activity. Herein, we aimed to disclose the role of histamine in microglial phagocytic activity and reactive oxygen species (ROS) production and to explore the consequences of histamine-induced neuroinflammation in dopaminergic (DA) neuronal survival. The effect of histamine on phagocytosis was assessed both in vitro by using a murine N9 microglial cell line and primary microglial cell cultures and in vivo. Cells were exposed to IgG-opsonized latex beads or phosphatidylserine (PS) liposomes to evaluate Fcγ or PS receptor-mediated microglial phagocytosis, respectively. ROS production and protein levels of NADPH oxidases and Rac1 were assessed as a measure of oxidative stress. DA neuronal survival was evaluated in vivo by counting the number of tyrosine hydroxylase-positive neurons in the substantia nigra (SN) of mice. We found that histamine triggers microglial phagocytosis via histamine receptor 1 (H1R) activation and ROS production via H1R and H4R activation. By using apocynin, a broad NADPH oxidase (Nox) inhibitor, and Nox1 knockout mice, we found that the Nox1 signaling pathway is involved in both phagocytosis and ROS production induced by histamine in vitro. Interestingly, both apocynin and annexin V (used as inhibitor of PS-induced phagocytosis) fully abolished the DA neurotoxicity induced by the injection of histamine in the SN of adult mice in vivo. Blockade of H1R protected against histamine-induced Nox1 expression and death of DA neurons in vivo. Overall, our results highlight the relevance of histamine in the modulation of microglial activity that ultimately may interfere with neuronal survival in the context of Parkinson's disease (PD) and, eventually, other neurodegenerative diseases which are accompanied by microglia

Effect of histamine H1 and H2 receptor antagonists, microinjected into cerebellar vermis, on emotional memory consolidation in mice

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A.C.L. Gianlorenco

2014-02-01

Full Text Available This study investigated the effects of histamine H1 or H2 receptor antagonists on emotional memory consolidation in mice submitted to the elevated plus maze (EPM. The cerebellar vermis of male mice (Swiss albino was implanted using a cannula guide. Three days after recovery, behavioral tests were performed in the EPM on 2 consecutive days (T1 and T2. Immediately after exposure to the EPM (T1, animals received a microinjection of saline (SAL or the H1 antagonist chlorpheniramine (CPA; 0.016, 0.052, or 0.16 nmol/0.1 µL in Experiment 1, and SAL or the H2 antagonist ranitidine (RA; 0.57, 2.85, or 5.7 nmol/0.1 µL in Experiment 2. Twenty-four hours later, mice were reexposed to the EPM (T2 under the same experimental conditions but they did not receive any injection. Data were analyzed using one-way ANOVA and the Duncan test. In Experiment 1, mice microinjected with SAL and with CPA entered the open arms less often (%OAE and spent less time in the open arms (%OAT in T2, and there was no difference among groups. The results of Experiment 2 demonstrated that the values of %OAE and %OAT in T2 were lower compared to T1 for the groups that were microinjected with SAL and 2.85 nmol/0.1 µL RA. However, when animals were microinjected with 5.7 nmol/0.1 µL RA, they did not show a reduction in %OAE and %OAT. These results demonstrate that CPA did not affect behavior at the doses used in this study, while 5.7 nmol/0.1 µL RA induced impairment of memory consolidation in the EPM.

Effect of histamine H1 and H2 receptor antagonists, microinjected into cerebellar vermis, on emotional memory consolidation in mice

International Nuclear Information System (INIS)

Gianlorenço, A.C.L.; Serafim, K.R.; Canto-de-Souza, A.; Mattioli, R.

2014-01-01

This study investigated the effects of histamine H1 or H2 receptor antagonists on emotional memory consolidation in mice submitted to the elevated plus maze (EPM). The cerebellar vermis of male mice (Swiss albino) was implanted using a cannula guide. Three days after recovery, behavioral tests were performed in the EPM on 2 consecutive days (T1 and T2). Immediately after exposure to the EPM (T1), animals received a microinjection of saline (SAL) or the H1 antagonist chlorpheniramine (CPA; 0.016, 0.052, or 0.16 nmol/0.1 µL) in Experiment 1, and SAL or the H2 antagonist ranitidine (RA; 0.57, 2.85, or 5.7 nmol/0.1 µL) in Experiment 2. Twenty-four hours later, mice were reexposed to the EPM (T2) under the same experimental conditions but they did not receive any injection. Data were analyzed using one-way ANOVA and the Duncan test. In Experiment 1, mice microinjected with SAL and with CPA entered the open arms less often (%OAE) and spent less time in the open arms (%OAT) in T2, and there was no difference among groups. The results of Experiment 2 demonstrated that the values of %OAE and %OAT in T2 were lower compared to T1 for the groups that were microinjected with SAL and 2.85 nmol/0.1 µL RA. However, when animals were microinjected with 5.7 nmol/0.1 µL RA, they did not show a reduction in %OAE and %OAT. These results demonstrate that CPA did not affect behavior at the doses used in this study, while 5.7 nmol/0.1 µL RA induced impairment of memory consolidation in the EPM

Effect of histamine H1 and H2 receptor antagonists, microinjected into cerebellar vermis, on emotional memory consolidation in mice

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Gianlorenço, A.C.L.; Serafim, K.R. [Laboratório de Neurociências, Departamento de Fisioterapia, Centro de Ciências Biológicas e da Saúde, Universidade Federal de São Carlos, São Carlos, SP, Brasil, Laboratório de Neurociências, Departamento de Fisioterapia, Centro de Ciências Biológicas e da Saúde, Universidade Federal de São Carlos, São Carlos, SP (Brazil); Canto-de-Souza, A. [Laboratório de Psicologia da Aprendizagem, Departamento de Psicologia, Centro de Educação e Ciências Humanas, Universidade Federal de São Carlos, São Carlos, SP, Brasil, Laboratório de Psicologia da Aprendizagem, Departamento de Psicologia, Centro de Educação e Ciências Humanas, Universidade Federal de São Carlos, São Carlos, SP (Brazil); Programa de Pós-Graduação em Ciências Fisiológicas, Universidade Federal de São Carlos, São Carlos, SP, Brasil, Programa de Pós-Graduação em Ciências Fisiológicas, Universidade Federal de São Carlos, São Carlos, SP (Brazil); Instituto de Neurociências e Comportamento, Universidade de São Paulo, Ribeirão Preto, SP, Brasil, Instituto de Neurociências e Comportamento, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Mattioli, R. [Laboratório de Neurociências, Departamento de Fisioterapia, Centro de Ciências Biológicas e da Saúde, Universidade Federal de São Carlos, São Carlos, SP, Brasil, Laboratório de Neurociências, Departamento de Fisioterapia, Centro de Ciências Biológicas e da Saúde, Universidade Federal de São Carlos, São Carlos, SP (Brazil)

2014-02-17

This study investigated the effects of histamine H1 or H2 receptor antagonists on emotional memory consolidation in mice submitted to the elevated plus maze (EPM). The cerebellar vermis of male mice (Swiss albino) was implanted using a cannula guide. Three days after recovery, behavioral tests were performed in the EPM on 2 consecutive days (T1 and T2). Immediately after exposure to the EPM (T1), animals received a microinjection of saline (SAL) or the H1 antagonist chlorpheniramine (CPA; 0.016, 0.052, or 0.16 nmol/0.1 µL) in Experiment 1, and SAL or the H2 antagonist ranitidine (RA; 0.57, 2.85, or 5.7 nmol/0.1 µL) in Experiment 2. Twenty-four hours later, mice were reexposed to the EPM (T2) under the same experimental conditions but they did not receive any injection. Data were analyzed using one-way ANOVA and the Duncan test. In Experiment 1, mice microinjected with SAL and with CPA entered the open arms less often (%OAE) and spent less time in the open arms (%OAT) in T2, and there was no difference among groups. The results of Experiment 2 demonstrated that the values of %OAE and %OAT in T2 were lower compared to T1 for the groups that were microinjected with SAL and 2.85 nmol/0.1 µL RA. However, when animals were microinjected with 5.7 nmol/0.1 µL RA, they did not show a reduction in %OAE and %OAT. These results demonstrate that CPA did not affect behavior at the doses used in this study, while 5.7 nmol/0.1 µL RA induced impairment of memory consolidation in the EPM.

Neuroprotective effect of lurasidone via antagonist activities on histamine in a rat model of cranial nerve involvement.

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He, Baoming; Yu, Liang; Li, Suping; Xu, Fei; Yang, Lili; Ma, Shuai; Guo, Yi

2018-04-01

Cranial nerve involvement frequently involves neuron damage and often leads to psychiatric disorder caused by multiple inducements. Lurasidone is a novel antipsychotic agent approved for the treatment of cranial nerve involvement and a number of mental health conditions in several countries. In the present study, the neuroprotective effect of lurasidone by antagonist activities on histamine was investigated in a rat model of cranial nerve involvement. The antagonist activities of lurasidone on serotonin 5‑HT7, serotonin 5‑HT2A, serotonin 5‑HT1A and serotonin 5‑HT6 were analyzed, and the preclinical therapeutic effects of lurasidone were examined in a rat model of cranial nerve involvement. The safety, maximum tolerated dose (MTD) and preliminary antitumor activity of lurasidone were also assessed in the cranial nerve involvement model. The therapeutic dose of lurasidone was 0.32 mg once daily, administered continuously in 14‑day cycles. The results of the present study found that the preclinical prescriptions induced positive behavioral responses following treatment with lurasidone. The MTD was identified as a once daily administration of 0.32 mg lurasidone. Long‑term treatment with lurasidone for cranial nerve involvement was shown to improve the therapeutic effects and reduce anxiety in the experimental rats. In addition, treatment with lurasidone did not affect body weight. The expression of the language competence protein, Forkhead‑BOX P2, was increased, and the levels of neuroprotective SxIP motif and microtubule end‑binding protein were increased in the hippocampal cells of rats with cranial nerve involvement treated with lurasidone. Lurasidone therapy reinforced memory capability and decreased anxiety. Taken together, lurasidone treatment appeared to protect against language disturbances associated with negative and cognitive impairment in the rat model of cranial nerve involvement, providing a basis for its use in the clinical treatment of

Histamine, carbachol, and serotonin induce hyperresponsiveness to ATP in guinea pig tracheas: involvement of COX-2 pathway.

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Montaño, Luis M; Carbajal, Verónica; Vargas, Mario H; García-Hernández, Luz M; Díaz-Hernández, Verónica; Checa, Marco; Barajas-López, Carlos

2013-08-01

Extracellular ATP promotes an indirect contraction of airway smooth muscle via the secondary release of thromboxane A2 (TXA2) from airway epithelium. Our aim was to evaluate if common contractile agonists modify this response to ATP. Tracheas from sensitized guinea pigs were used to evaluate ATP-induced contractions before and after a transient contraction produced by histamine, carbachol, or serotonin. Epithelial mRNA for COX-1 and COX-2 was measured by RT-PCR and their expression assessed by immunohistochemistry. Compared with the initial response, ATP-induced contraction was potentiated by pretreatment with histamine, carbachol, or serotonin. Either suramin (antagonist of P2X and P2Y receptors) plus RB2 (antagonist of P2Y receptors) or indomethacin (inhibitor of COX-1 and COX-2) annulled the ATP-induced contraction, suggesting that it was mediated by P2Y receptor stimulation and TXA2 production. When COX-2 was inhibited by SC-58125 or thromboxane receptors were antagonized by SQ-29548, just the potentiation was abolished, leaving the basal response intact. Airway epithelial cells showed increased COX-2 mRNA after stimulation with histamine or carbachol, but not serotonin, while COX-1 mRNA was unaffected. Immunochemistry corroborated this upregulation of COX-2. In conclusion, we showed for the first time that histamine and carbachol cause hyperresponsiveness to ATP by upregulating COX-2 in airway epithelium, which likely increases TXA2 production. Serotonin-mediated hyperresponsiveness seems to be independent of COX-2 upregulation, but nonetheless is TXA2 dependent. Because acetylcholine, histamine, and serotonin can be present during asthmatic exacerbations, their potential interactions with ATP might be relevant in its pathophysiology.

Antiallergic effects of H1-receptor antagonists.

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Baroody, F M; Naclerio, R M

2000-01-01

The primary mechanism of antihistamine action in the treatment of allergic diseases is believed to be competitive antagonism of histamine binding to cellular receptors (specifically, the H1-receptors), which are present on nerve endings, smooth muscles, and glandular cells. This notion is supported by the fact that structurally unrelated drugs antagonize the H1-receptor and provide clinical benefit. However, H1-receptor antagonism may not be their sole mechanism of action in treating allergic rhinitis. On the basis of in vitro and animal experiments, drugs classified as H1-receptor antagonists have long been recognized to have additional pharmacological properties. Most first-generation H1-antihistamines have anticholinergic, sedative, local anaesthetic, and anti-5-HT effects, which might favourably affect the symptoms of the allergic response but also contribute to side-effects. These additional properties are not uniformly distributed among drugs classified as H1-receptor antagonists. Azatadine, for example, inhibits in vitro IgE-mediated histamine and leukotriene (LT) release from mast cells and basophils. In human challenge models, terfenadine, azatadine, and loratadine reduce IgE-mediated histamine release. Cetirizine reduces eosinophilic infiltration at the site of antigen challenge in the skin, but not the nose. In a nasal antigen challenge model, cetirizine pretreatment did not affect the levels of histamine and prostaglandin D2 recovered in postchallenge lavages, whereas the levels of albumin, N-tosyl-L-arginine methyl ester (TAME) esterase activity, and LTs were reduced. Terfenadine, cetirizine, and loratadine blocked allergen-induced hyperresponsiveness to methacholine. In view of the complexity of the pathophysiology of allergy, a number of H1 antagonists with additional properties are currently under development for allergic diseases. Mizolastine, a new H1-receptor antagonist, has been shown to have additional actions that should help reduce the

Radiosynthesis and biodistribution of a histamine H3 receptor antagonist 4-[3-(4-piperidin-1-yl-but-1-ynyl)-[11C]benzyl]-morpholine: evaluation of a potential PET ligand

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Airaksinen, Anu J.; Jablonowski, Jill A.; Mey, Margreet van der; Barbier, Ann J.; Klok, Rob P.; Verbeek, Joost; Schuit, Robert; Herscheid, Jacobus D.M.; Leysen, Josee E.; Carruthers, Nicholas I.; Lammertsma, Adriaan A.; Windhorst, Albert D.

2006-01-01

The potent histamine H 3 receptor antagonist JNJ-10181457 () was successfully labeled with 11 C in a novel one-pot reaction sequence, with high chemical yield (decay-corrected yield, 28±8%) and high specific radioactivity (56±26 GBq/μmol). The binding of [ 11 C] to H 3 receptors was studied in vitro in rat brain and in vivo in rats and mice. The in vitro binding of [ 11 C] in rat coronal brain slices showed high binding in the striatum, and this binding was blocked by histamine and by two known H 3 antagonists, JNJ-5207852 () and unlabeled Compound (), in a concentration-dependent manner. The biodistribution of [ 11 C] in rats was measured at 5, 10, 30 and 60 min. The uptake of [ 11 C] in regions rich in H 3 receptors was highest at 30 min, giving 0.98%, 1.41%, 1.28% and 1.72% dose/g for the olfactory bulb, hippocampus, striatum and cerebral cortex, respectively. However, the binding of [ 11 C] in the rat brain could not be blocked by pretreatment with either Compound () (30 min or 24 h pretreatment) or cold Compound () (30-min pretreatment). The biodistribution of [ 11 C] in a second species (Balb/c mice) showed a higher overall uptake of the radioligand with an average brain uptake of 8.9% dose/g. In C57BL/6-H 3 (-/-) knockout mice, a higher brain uptake was also observed. Analyses of metabolites and plasma protein binding were also undertaken. It appeared that [ 11 C] could not specifically label H 3 receptors in rodent brain in vivo. Possible causes are discussed

Histamine fish poisoning revisited.

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Lehane, L; Olley, J

2000-06-30

Histamine (or scombroid) fish poisoning (HFP) is reviewed in a risk-assessment framework in an attempt to arrive at an informed characterisation of risk. Histamine is the main toxin involved in HFP, but the disease is not uncomplicated histamine poisoning. Although it is generally associated with high levels of histamine (> or =50 mg/100 g) in bacterially contaminated fish of particular species, the pathogenesis of HFP has not been clearly elucidated. Various hypotheses have been put forward to explain why histamine consumed in spoiled fish is more toxic than pure histamine taken orally, but none has proved totally satisfactory. Urocanic acid, like histamine, an imidazole compound derived from histidine in spoiling fish, may be the "missing factor" in HFP. cis-Urocanic acid has recently been recognised as a mast cell degranulator, and endogenous histamine from mast cell degranulation may augment the exogenous histamine consumed in spoiled fish. HFP is a mild disease, but is important in relation to food safety and international trade. Consumers are becoming more demanding, and litigation following food poisoning incidents is becoming more common. Producers, distributors and restaurants are increasingly held liable for the quality of the products they handle and sell. Many countries have set guidelines for maximum permitted levels of histamine in fish. However, histamine concentrations within a spoiled fish are extremely variable, as is the threshold toxic dose. Until the identity, levels and potency of possible potentiators and/or mast-cell-degranulating factors are elucidated, it is difficult to establish regulatory limits for histamine in foods on the basis of potential health hazard. Histidine decarboxylating bacteria produce histamine from free histidine in spoiling fish. Although some are present in the normal microbial flora of live fish, most seem to be derived from post-catching contamination on board fishing vessels, at the processing plant or in the

Evaluation of in vivo selective binding of [11C]doxepin to histamine H1 receptors in five animal species

International Nuclear Information System (INIS)

Ishiwata, Kiichi; Kawamura, Kazunori; Wang Weifang; Tsukada, Hideo; Harada, Norihiro; Mochizuki, Hideki; Kimura, Yuichi; Ishii, Kenji; Iwata, Ren; Yanai, Kazuhiko

2004-01-01

The specific binding of [ 11 C]doxepin, which has been used as a radioligand for mapping histamine H 1 receptors in human brain by positron emission tomography, was evaluated in five animal species. In mice the [ 11 C]doxepin uptake was reduced by treatment with cold doxepin and two H 1 receptor antagonists, but not with H 2 /H 3 antagonists. The specific binding evaluated with treatment with (+)-chlorpheniramine (H 1 antagonist) was in the range of 10-30% in mouse, rat, rabbit, and monkey, but was not detected in guinea pig

Histamine from brain resident MAST cells promotes wakefulness and modulates behavioral states.

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Sachiko Chikahisa

Full Text Available Mast cell activation and degranulation can result in the release of various chemical mediators, such as histamine and cytokines, which significantly affect sleep. Mast cells also exist in the central nervous system (CNS. Since up to 50% of histamine contents in the brain are from brain mast cells, mediators from brain mast cells may significantly influence sleep and other behaviors. In this study, we examined potential involvement of brain mast cells in sleep/wake regulations, focusing especially on the histaminergic system, using mast cell deficient (W/W(v mice. No significant difference was found in the basal amount of sleep/wake between W/W(v mice and their wild-type littermates (WT, although W/W(v mice showed increased EEG delta power and attenuated rebound response after sleep deprivation. Intracerebroventricular injection of compound 48/80, a histamine releaser from mast cells, significantly increased histamine levels in the ventricular region and enhanced wakefulness in WT mice, while it had no effect in W/W(v mice. Injection of H1 antagonists (triprolidine and mepyramine significantly increased the amounts of slow-wave sleep in WT mice, but not in W/W(v mice. Most strikingly, the food-seeking behavior observed in WT mice during food deprivation was completely abolished in W/W(v mice. W/W(v mice also exhibited higher anxiety and depression levels compared to WT mice. Our findings suggest that histamine released from brain mast cells is wake-promoting, and emphasizes the physiological and pharmacological importance of brain mast cells in the regulation of sleep and fundamental neurobehavior.

Activation of adenosine low-affinity A3 receptors inhibits the enteric short interplexus neural circuit triggered by histamine.

Science.gov (United States)

Bozarov, Andrey; Wang, Yu-Zhong; Yu, Jun Ge; Wunderlich, Jacqueline; Hassanain, Hamdy H; Alhaj, Mazin; Cooke, Helen J; Grants, Iveta; Ren, Tianhua; Christofi, Fievos L

2009-12-01

We tested the novel hypothesis that endogenous adenosine (eADO) activates low-affinity A3 receptors in a model of neurogenic diarrhea in the guinea pig colon. Dimaprit activation of H2 receptors was used to trigger a cyclic coordinated response of contraction and Cl(-) secretion. Contraction-relaxation was monitored by sonomicrometry (via intracrystal distance) simultaneously with short-circuit current (I(sc), Cl(-) secretion). The short interplexus reflex coordinated response was attenuated or abolished by antagonists at H2 (cimetidine), 5-hydroxytryptamine 4 receptor (RS39604), neurokinin-1 receptor (GR82334), or nicotinic (mecamylamine) receptors. The A1 agonist 2-chloro-N(6)-cyclopentyladenosine (CCPA) abolished coordinated responses, and A1 antagonists could restore normal responses. A1-selective antagonists alone [8-cyclopentyltheophylline (CPT), 1,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine (PACPX), or 8-cyclopentyl-N(3)-[3-(4-(fluorosulfonyl)benzoyloxy)propyl]-xanthine (FSCPX)] caused a concentration-dependent augmentation of crypt cell secretion or contraction and acted at nanomolar concentrations. The A3 agonist N(6)-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (IB-MECA) abolished coordinated responses and the A3 antagonist 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(+/-)-dihydropyridine-3,5-dicarboxylate (MRS1191) could restore and further augment responses. The IB-MECA effect was resistant to knockdown of adenosine A1 receptor with the irreversible antagonist FSCPX; the IC(50) for IB-MECA was 0.8 microM. MRS1191 alone could augment or unmask coordinated responses to dimaprit, and IB-MECA suppressed them. MRS1191 augmented distension-evoked reflex I(sc) responses. Adenosine deaminase mimicked actions of adenosine receptor antagonists. A3 receptor immunoreactivity was differentially expressed in enteric neurons of different parts of colon. After tetrodotoxin, IB-MECA caused circular muscle relaxation. The data support the novel concept that

The effects of histamine and prostaglandin D2 on rat mast-cell cyclic AMP and mediator release

International Nuclear Information System (INIS)

Wescott, S.; Kaliner, M.

1981-01-01

The possibility that histamine may play a functional role in modulating mast-cell secretion, as has been suggested for basophil degranulation, has both physiologic and pharmacologic implications. Therefore the capacity of histamine to influence rat peritoneal mast-cell (RPMC) cyclic AMP levels and reversed anaphylatic degranulation as reflected in the release of 3H-serotonin (5-HT) was examined. To ascertain that RPMC were functionally responsive to exogenous hormonal stimulation, assessment of prostaglandin (PG) D2 effects on cyclic AMP and 5-HT release were determined in parallel. Although PGD2 (100 microM) increased cyclic AMP and inhibited 5-HT release in the presence of 50 microM aminophylline, histamine (up to 1000 microM) was ineffective was ineffective in both. However, 1000 microM histamine in the presence of 500 microM aminophylline was capable of transiently increasing RPMC cyclic AMP (for 15 to 30 sec) and under these conditions of suppressing 5-HT release. The receptor subtype involved in the suppressive actions of histamine appeared to be of the H-1 type as reflected in the capacity of specific H-1 agonists to reproduce the inhibition of 5-HT release, whereas neither H-2 agonists nor H-2 antagonists had any influence. Thus, under conditions in which phosphodiesterase enzymatic action is impaired, histamine in extremely high concentrations is able to modulate mast-cell secretion. However, it seems very unlikely that this action of histamine has any physiologic significance

Effects of histamine H1 receptor signaling on glucocorticoid receptor activity. Role of canonical and non-canonical pathways

NARCIS (Netherlands)

Zappia, C.D.; Granja-Galeano, G.; Fernández, N.; Shayo, C.; Davio, C.; Fitzsimons, C.P.; Monczor, F.

2015-01-01

Histamine H1 receptor (H1R) antagonists and glucocorticoid receptor (GR) agonists are used to treat inflammatory conditions such as allergic rhinitis, atopic dermatitis and asthma. Consistent with the high morbidity levels of such inflammatory conditions, these receptors are the targets of a vast

Potential negative effects of anti-histamines on male reproductive function.

Science.gov (United States)

Mondillo, Carolina; Varela, María Luisa; Abiuso, Adriana María Belén; Vázquez, Ramiro

2018-05-01

Histamine (HA) is a pleiotropic biogenic amine synthesized exclusively by histidine decarboxylase (HDC) in most mammalian tissues. The literature on the role of HA within the male gonad has expanded over the last years, attracting attention to potential unexpected side-effects of anti-histamines on testicular function. In this regard, HA receptors (HRH1, HRH2 and HRH4) have been described in Leydig cells of different species, including human. Via these receptors, HA has been reported to trigger positive or negative interactions with the LH/hCG signaling pathway depending upon its concentration, thereby contributing to the local control of testicular androgen levels. It should then be considered that anti-histamines may affect testicular homeostasis by increasing or decreasing steroid production. Additionally, HRH1 and HRH2 receptors are present in peritubular and germ cells, and HRH2 antagonists have been found to negatively affect peritubular cells and reduce sperm viability. The potential negative impact of anti-histamines on male reproduction becomes even more dramatic if we consider that HA has also been associated with human sexual behavior and penile erection. What is more, although testicular mast cells are the major source of locally produced HA, recent studies have described HDC expression in macrophages, Leydig cells and germ cells, revealing the existence of multiple sources of HA within the testis. Undoubtedly, the more we learn about the testicular histaminergic system, the more opportunities there will be for rational design of drugs aimed at treating HA-related pathologies, with minimum or nule negative impact on fertility. © 2018 Society for Reproduction and Fertility.

The histamine content of oriental foods.

Science.gov (United States)

Chin, K W; Garriga, M M; Metcalfe, D D

1989-05-01

Several of the symptoms of scombroid poisoning (i.e. histamine toxicity) resemble those observed in people suffering from Chinese restaurant syndrome. Therefore, the histamine content of representative Chinese cuisine, which included 31 common dishes, 12 condiments and 12 basic ingredients from several sources, was measured using a sensitive and specific radioenzymatic assay. A further enzymatic procedure involving diamine oxidase was used to verify that the substance measured was histamine. A total of 184 assays were performed on 57 samples in the study. High levels of histamine were found in the cheeses, which were used as positive controls (863.6 micrograms histamine/g blue cheese and 107.4 micrograms histamine/g Parmesan cheese), and in some common condiments, including tamari (2392.2 micrograms histamine/g sample) and one brand of soy sauce (220.4 micrograms histamine/g sample). The histamine content of four condiments and three common dishes was over 10 micrograms histamine/g sample, while four condiments and 16 common dishes contained less than 1 microgram histamine/g sample. Calculations involving representative amounts of food that can be consumed at a typical oriental meal suggest that, in some cases, histamine intake may approach toxic levels. The results are discussed with regard to the possible role of histamine in reactions associated with restaurant meals.

In vitro H1-receptor antagonist activity of methanolic extract of tuber of Stephania glabra

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Nisar Ahmad Khan

2010-06-01

Full Text Available In the present study, methanolic extract of tuber of Stephania glabra was evaluated for H1-bloker activity by employing in vitro screening models of guinea pig ileum and goat tracheal chain preparation. Goat isolated trachea and guinea pig ileum contracted to histamine in a dose-dependent manner while chlorpheniramine blocked this effect. The methanolic extract produced significant dose-dependent H1-receptor antagonist activity by blocking histamine-induced contraction.

Histamine H3 receptor: A novel therapeutic target in alcohol dependence?

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Pertti ePanula

2012-05-01

Full Text Available The brain histaminergic system is one of the diffuse modulatory neurotransmitter systems which regulate neuronal activity in many brain areas. Studies on both rats and mice indicate that histamine H3 receptor antagonists decrease alcohol drinking in several models, like operant alcohol administration and drinking in the dark paradigm. Alcohol-induced place preference is also affected by these drugs. Moreover, mice lacking H3R do not drink alcohol like their wild type littermates, and they do not show alcohol-induced place preference. Although the mechanisms of these behaviors are still being investigated, we propose that H3R antagonists are promising candidates for use in human alcoholics, as these drugs are already tested for treatment of other disorders like narcolepsy and sleep disorders.

Immunoregulatory T cells in man. Histamine-induced suppressor T cells are derived from a Leu 2+ (T8+) subpopulation distinct from that which gives rise to cytotoxic T cells

International Nuclear Information System (INIS)

Sansoni, P.; Silverman, E.D.; Khan, M.M.; Melmon, K.L.; Engleman, E.G.

1985-01-01

One mechanism of histamine-mediated inhibition of the immune response in man is to activate T suppressor cells that bear the Leu 2 (OKT8) marker. The current study was undertaken to characterize the histamine-induced suppressor cell using a monoclonal antibody (9.3) shown previously to distinguish cytotoxic T cells from antigen-specific suppressor T cells. Leu 2+ cells isolated from peripheral blood were further separated with antibody 9.3 into Leu 2+, 9.3+, and Leu 2+, 9.3- subsets and each subset was incubated with different concentrations of histamine before determining their ability to suppress immune responses in vitro. The results indicate that the Leu 2+, 9.3- subpopulation includes all histamine-induced suppressor cells, that 10(-4) M histamine is the optimal concentration for suppressor cell induction, and that exposure of Leu 2+, 9.3- cells to histamine for 30 s is sufficient to initiate the induction process. After treatment with histamine these cells inhibit both phytohemagglutinin-induced T cell proliferation and pokeweed mitogen-induced B cell differentiation. The suppression of phytohemagglutinin-induced proliferation was resistant to x-irradiation with 1,200 rad, either before or after histamine exposure, suggesting that Leu 2+, 9.3- cells need not proliferate to become suppressor cells or exert suppression. Moreover, suppression by these cells was not due to altered kinetics of the response. Finally, a histamine type 2 receptor antagonist (cimetidine) but not a type 1 receptor antagonist (mepyramine) blocked the induction of suppressor cells. On the basis of these results and our previous studies of antigen specific suppressor cells, we conclude that Leu 2+ suppressor cells in man are derived from a precursor pool that is phenotypically distinct from cells that can differentiate into cytotoxic T cells

Histamine metabolism in cluster headache and migraine. Catabolism of /sup 14/C histamine

Energy Technology Data Exchange (ETDEWEB)

Sjaastad, O; Sjaastad, O V

1977-09-12

Various parameters of histamine metabolism were studied in patients with migraine, cluster headache and chronic paroxysmal hemicrania. These included urinary excretion of radioactivity and of /sup 14/C histamine and its metabolites, exhaled /sup 14/CO/sub 2/ and fecal radioactivity after oral as well as subcutaneous administration of radioactive histamine. No marked deviation from the normal was found except in one patient with the cluster headache variant, chronic paroxysmal hemicrania, in whom an aberration in /sup 14/C histamine degradation seemed to be present. Only minute quantities of the /sup 14/C histamine metabolite C14 imidazoleacetic acid riboside seemed to be formed during a period with severe paraxysms. During a symptom-free period no deviation from normal was observed. The most likely explanation for this finding seems to be a defect in the conversion of imidazoleacetic acid to its riboside. This defect may possibly explain the increased urinary excretion of histamine in this particular patient. The relationship of this metabolic aberration to the production of headache still remains dubious for various reasons.

Mast cell histamine-mediated transient inflammation following exposure to nickel promotes nickel allergy in mice.

Science.gov (United States)

Kinbara, Masayuki; Bando, Kanan; Shiraishi, Daisuke; Kuroishi, Toshinobu; Nagai, Yasuhiro; Ohtsu, Hiroshi; Takano-Yamamoto, Teruko; Sugawara, Shunji; Endo, Yasuo

2016-06-01

We previously reported that allergic responses to nickel (Ni) were minimal in mice deficient in the histamine-forming enzyme histidine decarboxylase (HDC-KO), suggesting an involvement of histamine in allergic responses to Ni. However, it remains unclear how histamine is involved in the process of Ni allergy. Here, we examined the role of histamine in Ni allergy using a murine model previously established by us. Mice were sensitized to Ni by intraperitoneal injection of a NiCl2 -lipopolysaccharide (LPS) mixture. Ten days later, allergic inflammation was elicited by challenging ear-pinnas intradermally with NiCl2 . Then, ear-swelling was measured. Pyrilamine (histamine H1-receptor antagonist) or cromoglicate (mast cell stabilizer) was intravenously injected 1 h before the sensitization or the challenge. In cell-transfer experiments, spleen cells from Ni-sensitized donor mice were intravenously transferred into non-sensitized recipient mice. In both sensitized and non-sensitized mice, 1 mm or more NiCl2 (injected into ear-pinnas) induced transient non-allergic inflammation (Ni-TI) with accompanying mast cell degranulation. LPS did not affect the magnitude of this Ni-TI. Pyrilamine and cromoglicate reduced either the Ni-TI or the ensuing allergic inflammation when administered before Ni-TI (at either the sensitization or elicitation step), but not if administered when the Ni-TI had subsided. Experiments on HDC-KO and H1-receptor-KO mice, and also cell-transfer experiments using these mice, demonstrated histamine's involvement in both the sensitization and elicitation steps. These results suggest that mast cell histamine-mediated Ni-TI promotes subsequent allergic inflammatory responses to Ni, raising the possibility that control of Ni-TI by drugs may be effective at preventing or reducing Ni allergy. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Tryptase potentiates enteric nerve activation by histamine and serotonin: Relevance for the effects of mucosal biopsy supernatants from irritable bowel syndrome patients.

Science.gov (United States)

Ostertag, D; Annahazi, A; Krueger, D; Michel, K; Demir, I E; Ceyhan, G O; Zeller, F; Schemann, M

2017-09-01

We previously showed that mucosal biopsy supernatants from irritable bowel syndrome patients activated neurons despite low concentrations of tryptase, histamine, and serotonin which individually would not cause spike discharge. We studied the potentiating responses between these mediators on excitability of enteric neurons. Calcium-imaging was performed using the calcium-sensitive dye Fluo-4 AM in human submucous plexus preparations from 45 individuals. Histamine, serotonin, and tryptase were applied alone and in combinations to evaluate nerve activation which was assessed by analyzing increase in intracellular Ca 2+ ([Ca 2+ ] i ), the proportion of responding neurons and the product of both defined as Ca-neuroindex (NI). Protease activated receptor (PAR) 2 activating peptide, PAR2 antagonist and the serine protease-inhibitor FUT-175 were used to particularly investigate the role of proteases. Histamine or serotonin (1 μmol/L each) evoked only few small responses (median NI [25%/75%]: 0 [0/148]; 85 [0/705] respectively). Their combined application evoked statistically similar responses (216 [21/651]). Addition of the PAR2 activator tryptase induced a significantly higher Ca-NI (1401 [867/4075]) compared to individual application of tryptase or to coapplied histamine and serotonin. This synergistic potentiation was neither mimicked by PAR2 activating peptide nor reversed by the PAR2 antagonist GB83, but abolished by FUT-175. We observed synergistic potentiation between histamine, serotonin, and tryptase in enteric neurons, which is mediated by proteolytic activity rather than PAR2 activation. This explained neuronal activation by a cocktail of these mediators despite their low concentrations and despite a relatively small PAR2-mediated response in human submucous neurons. © 2017 John Wiley & Sons Ltd.

Histamine and Tyramine in Food.

Science.gov (United States)

1985-05-01

FISH PRODUCTS 44 ON THE JAPANESE MARKET TABLE 4-9 TYRAMINE AND HISTAMINE IN FRUITS, 48 VEGETABLES AND THEIR PRODUCTS TABLE 5-1 SCOMBROTOXIN (HISTAMINE...Products The histamine and tyramine content of fruits, vegetables and their products is shown in Table 4-9. The fruits of avocado , lemon, and...VEGETABLES, AND THEIR PRODUCTS (ug/g) ITEM HISTAMINE TYRAMINE REFERENCE Apple 0 6 Avocado 23 78 Bananas 7 79, 80, 81, 82 Banana Peel - 65 81 Barley - 10

Comparison of methods for intestinal histamine application

DEFF Research Database (Denmark)

Vind, S; Søondergaard, I; Poulsen, L K

1991-01-01

The study was conducted to investigate whether introduction of histamine in enterosoluble capsules produced the same amount of urinary histamine metabolites as that found after application of histamine through a duodeno-jejunal tube. Secondly, to examine whether a histamine-restrictive or a fast ...... conclude that oral administration of enterosoluble capsules is an easy and appropriate method for intestinal histamine challenge. Fast and histamine-restrictive diets are not necessary, but subjects should record unexpected responses in a food and symptom diary.......The study was conducted to investigate whether introduction of histamine in enterosoluble capsules produced the same amount of urinary histamine metabolites as that found after application of histamine through a duodeno-jejunal tube. Secondly, to examine whether a histamine-restrictive or a fast...... all other intervals did not differ significantly between the two challenge regimens. Fast (water only) and histamine-restrictive diet versus non-restrictive diet did not affect the urinary MIAA. MIAA was significantly higher overall during the first 24 h after challenge than in any other fraction. We...

Radiosynthesis and biodistribution of a histamine H{sub 3} receptor antagonist 4-[3-(4-piperidin-1-yl-but-1-ynyl)-[{sup 11}C]benzyl]-morpholine: evaluation of a potential PET ligand

Energy Technology Data Exchange (ETDEWEB)

Airaksinen, Anu J. [Department of Nuclear Medicine and PET Research, Location Radionuclide Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam (Netherlands); Jablonowski, Jill A. [Johnson and Johnson Pharmaceutical Research and Development LLC, San Diego, CA 92121 (United States); Mey, Margreet van der [Department of Nuclear Medicine and PET Research, Location Radionuclide Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam (Netherlands); Barbier, Ann J. [Johnson and Johnson Pharmaceutical Research and Development LLC, San Diego, CA 92121 (United States); Klok, Rob P. [Department of Nuclear Medicine and PET Research, Location Radionuclide Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam (Netherlands); Verbeek, Joost [Department of Nuclear Medicine and PET Research, Location Radionuclide Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam (Netherlands); Schuit, Robert [Department of Nuclear Medicine and PET Research, Location Radionuclide Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam (Netherlands); Herscheid, Jacobus D.M. [Department of Nuclear Medicine and PET Research, Location Radionuclide Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam (Netherlands); Leysen, Josee E. [Department of Nuclear Medicine and PET Research, Location Radionuclide Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam (Netherlands); Carruthers, Nicholas I. [Johnson and Johnson Pharmaceutical Research and Development LLC, San Diego, CA 92121 (United States); Lammertsma, Adriaan A. [Department of Nuclear Medicine and PET Research, Location Radionuclide Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam (Netherlands); Windhorst, Albert D. [Department of Nuclear Medicine and PET Research, Location Radionuclide Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam (Netherlands)]. E-mail: bwindhorst@rnc.vu.nl

2006-08-15

The potent histamine H{sub 3} receptor antagonist JNJ-10181457 () was successfully labeled with {sup 11}C in a novel one-pot reaction sequence, with high chemical yield (decay-corrected yield, 28{+-}8%) and high specific radioactivity (56{+-}26 GBq/{mu}mol). The binding of [{sup 11}C] to H{sub 3} receptors was studied in vitro in rat brain and in vivo in rats and mice. The in vitro binding of [{sup 11}C] in rat coronal brain slices showed high binding in the striatum, and this binding was blocked by histamine and by two known H{sub 3} antagonists, JNJ-5207852 () and unlabeled Compound (), in a concentration-dependent manner. The biodistribution of [{sup 11}C] in rats was measured at 5, 10, 30 and 60 min. The uptake of [{sup 11}C] in regions rich in H{sub 3} receptors was highest at 30 min, giving 0.98%, 1.41%, 1.28% and 1.72% dose/g for the olfactory bulb, hippocampus, striatum and cerebral cortex, respectively. However, the binding of [{sup 11}C] in the rat brain could not be blocked by pretreatment with either Compound () (30 min or 24 h pretreatment) or cold Compound () (30-min pretreatment). The biodistribution of [{sup 11}C] in a second species (Balb/c mice) showed a higher overall uptake of the radioligand with an average brain uptake of 8.9% dose/g. In C57BL/6-H{sub 3}(-/-) knockout mice, a higher brain uptake was also observed. Analyses of metabolites and plasma protein binding were also undertaken. It appeared that [{sup 11}C] could not specifically label H{sub 3} receptors in rodent brain in vivo. Possible causes are discussed.

Evaluation of in vivo selective binding of [{sup 11}C]doxepin to histamine H{sub 1} receptors in five animal species

Energy Technology Data Exchange (ETDEWEB)

Ishiwata, Kiichi E-mail: ishiwata@pet.tmig.or.jp; Kawamura, Kazunori; Wang Weifang; Tsukada, Hideo; Harada, Norihiro; Mochizuki, Hideki; Kimura, Yuichi; Ishii, Kenji; Iwata, Ren; Yanai, Kazuhiko

2004-05-01

The specific binding of [{sup 11}C]doxepin, which has been used as a radioligand for mapping histamine H{sub 1} receptors in human brain by positron emission tomography, was evaluated in five animal species. In mice the [{sup 11}C]doxepin uptake was reduced by treatment with cold doxepin and two H{sub 1} receptor antagonists, but not with H{sub 2}/H{sub 3} antagonists. The specific binding evaluated with treatment with (+)-chlorpheniramine (H{sub 1} antagonist) was in the range of 10-30% in mouse, rat, rabbit, and monkey, but was not detected in guinea pig.

The Histamine H3 Receptor Antagonist DL77 Ameliorates MK801-Induced Memory Deficits in Rats

Directory of Open Access Journals (Sweden)

Nermin Eissa

2018-02-01

Full Text Available The role of Histamine H3 receptors (H3Rs in memory, and the prospective of H3R antagonists in pharmacological control of neurodegenerative disorders, e.g., Alzheimer disease (AD is well-accepted. For that reason, the procognitive effects of the H3R antagonist DL77 on cognitive impairments induced with MK801 were tested in an inhibitory passive avoidance paradigm (PAP and novel object recognition (NOR task in adult male rats, using donepezil (DOZ as a standard drug. Acute systemic pretreatment with DL77 (2.5, 5, and 10 mg/kg, i.p. significantly ameliorated memory deficits induced with MK801 in PAP (all P < 0.05, n = 7. The ameliorative effect of most promising dose of DL77 (5 mg/kg, i.p. was reversed when rats were co-injected with the H3R agonist R-(α-methylhistamine (RAMH, 10 mg/kg, i.p. (p = 0.701 for MK801-amnesic group vs. MK801+DL77+RAMH group, n = 6. In the NOR paradigm, DL77 (5 mg/kg, i.p. counteracted long-term memory (LTM deficits induced with MK801 (P < 0.05, n = 6–8, and the DL77-provided effect was similar to that of DOZ (p = 0.788, n = 6–8, and was reversed when rats were co-injected with RAMH (10 mg/kg, i.p. (p = 0.877, n = 6, as compared to the (MK801-amnesic group. However, DL77 (5 mg/kg, i.p. did not alter short-term memory (STM impairment in NOR test (p = 0.772, n = 6–8, as compared to (MK801-amnesic group. Moreover, DL77 (5 mg/kg failed to modify anxiety and locomotor behaviors of animals innate to elevated-plus maze (EPM (p = 0.67 for percentage of time spent exploring the open arms, p = 0.52 for number of entries into the open arms, p = 0.76 for percentage of entries into the open arms, and p = 0.73 number of closed arm entries as compared to saline-treated groups, all n = 6, demonstrating that the procognitive effects observed in PAP or NOR tests were unconnected to alterations in emotions or in natural locomotion of tested animals. These results signify the potential involvement of H3Rs in modulating

Fluorometric determination of histamine in cheese.

Science.gov (United States)

Chambers, T L; Staruszkiewicz, W F

1978-09-01

Thirty-one samples of cheese obtained from retail outlets were analyzed for histamine, using an official AOAC fluorometric method. The types of cheese analyzed and the ranges of histamine found were: colby, 0.3--2.8; camembert, 0.4--4.2; cheddar, 1.2--5.8; gouda, 1.3--2.4; provolone, 2.0--23.5; roquefort, 1.0--16.8; mozzarella 1.6--5.0; and swiss, 0.4--250 mg histamine/100 g. Ten of the 12 samples of swiss cheese contained less than 16 mg histamine/100 g. The remaining 2 samples which contained 116 and 250 mg histamine/100 g were judged organoleptically to be of poor quality. An investigation of one processing facility showed that the production of histamine in swiss cheese may have been a result of a hydrogen peroxide/low temperature treatment of the milk supply. Recovery of histamine added to methanol extracts of cheese ranged from 93 to 105%. Histamine content was confirmed by high pressure liquid chromatographic analysis of the methanol extracts.

6-[N,S-dimethyl-N'-cyanothioureidomethyl]-6,11-dihydro-5H- dibenz[b,e]azepine hydrochloride (Fran 12): a histamine and 5-hydroxytryptamine antagonist with pressor properties.

Science.gov (United States)

Law, S C; Guyett, F J; King, R G; Boura, A L; Jackson, W R; Hodgson, W C

1992-01-01

We have synthesized and examined some of the pharmacological properties of 6-[N,S-dimethyl-N'-cyanoisothioureidomethyl]-6,11-dihydro-5H- dibenz(b,e)azepine hydrochloride (Fran 12), a derivative of 6-methylaminomethyl-6,11-dihydro-5H- dibenz[b,e,]azepine. In the guinea-pig isolated ileum, Fran 12 (10(-7)-10(-5) M) caused parallel rightward shifts of the concentration-response curves to histamine. A Schild plot gave a pA2 of 7.48, with a slope not significantly different from -1.0. In the rat stomach fundus strip and in endothelium-denuded aortic rings, Fran 12 inhibited contractile responses to 5-hydroxytryptamine in a non-competitive manner. In both chloralose-anaesthetized and pithed rats, it inhibited pressor responses to 5-hydroxytryptamine. It had no effect on depressor responses to 5-hydroxytryptamine in anaesthetized rats. In pithed rats, Fran 12 (0.25-2 mg/kg, i.v.) produced dose-dependent increases in blood pressure. These were not inhibited by i.v. phentolamine, prazosin, yohimbine, propranolol, methysergide, pentolinium or atropine but were inhibited by verapamil. These results indicate that Fran 12 is a histamine and 5-hydroxytryptamine antagonist which also exerts pressor effects via a peripheral action. The pressor action does not appear to be mediated via effects on alpha 1- or alpha 2-adrenoceptors, muscarinic or nicotinic cholinoceptors or 5-hydroxytryptamine receptors, although calcium channel activation may play a role.

Molecular Regulation of Histamine Synthesis

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Hua Huang

2018-06-01

Full Text Available Histamine is a critical mediator of IgE/mast cell-mediated anaphylaxis, a neurotransmitter and a regulator of gastric acid secretion. Histamine is a monoamine synthesized from the amino acid histidine through a reaction catalyzed by the enzyme histidine decarboxylase (HDC, which removes carboxyl group from histidine. Despite the importance of histamine, transcriptional regulation of HDC gene expression in mammals is still poorly understood. In this review, we focus on discussing advances in the understanding of molecular regulation of mammalian histamine synthesis.

On histamine and appetites

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Fernando eTorrealba

2012-07-01

Full Text Available Brain histamine may influence a variety of different behavioral and physiological functions, but its responsibility in waking up has casted a long shadow on other important functions of this neurotransmitter. Here we review evidence indicating a central role of brain histamine in motivation, emphasizing its differential involvement in the appetitive and consummatory phases of motivated behaviors. We discuss the inputs that control the histaminergic neurons of the tuberomamillary nucleus of the hypothalamus, which determine the distinct role of these neurons in appetitive behavior, sleep/wake cycles and in food anticipatory activity. We review evidence supporting a dysfunction of histamine neurons and its cortical input in certain forms of decreased motivation (apathy. We finally discuss the relationship between the histamine system and drug addiction as a dysfunction of motivation.

Simultaneous detection of pH changes and histamine release from oxyntic glands in isolated stomach.

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Bitziou, Eleni; O'Hare, Danny; Patel, Bhavik Anil

2008-11-15

Real-time simultaneous detection of changes in pH and levels of histamine over the oxyntic glands of guinea pig stomach have been investigated. An iridium oxide pH microelectrode was used in a potentiometric mode to record the pH decrease associated with acid secretion when the sensor approached the isolated tissue. A boron-doped diamond (BDD) microelectrode was used in an amperometric mode to detect histamine when the electrode was placed over the tissue. Both sensors provided stable and reproducible responses that were qualitatively consistent with the signaling mechanism for acid secretion at the stomach. Simultaneous measurements in the presence of pharmacological treatments produced significant variations in the signals obtained by both sensors. As the H2 receptor antagonist cimetidine was perfused to the tissue, histamine levels increased that produced an increase in the signal of the BDD electrode whereas the pH sensor recorded a decrease in acid secretion as expected. Addition of acetylcholine (ACh) stimulated additional acid secretion detected with the pH microelectrode whereas the BDD sensor recorded the histamine levels decreasing significantly. This result shows that the primary influence of ACh is directly on the parietal cell receptors rather then the ECL cell receptors of the oxyntic glands. These results highlight the power of this simultaneous detection technique in the monitoring and diagnosis of physiological significant signaling mechanisms and pathways.

Vascular Effects of Histamine

African Journals Online (AJOL)

olayemitoyin

effects of histamine are mediated via H1 and H2 receptors and the actions are modulated by H3 receptor subtype located on presynaptic ... neurotransmittion in the central nervous system and .... Autoinhibition of brain histamine release.

The discovery of the benzazepine class of histamine H3 receptor antagonists.

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Wilson, David M; Apps, James; Bailey, Nicholas; Bamford, Mark J; Beresford, Isabel J; Briggs, Michael A; Calver, Andrew R; Crook, Barry; Davis, Robert P; Davis, Susannah; Dean, David K; Harris, Leanne; Heightman, Tom D; Panchal, Terry; Parr, Christopher A; Quashie, Nigel; Steadman, Jon G A; Schogger, Joanne; Sehmi, Sanjeet S; Stean, Tania O; Takle, Andrew K; Trail, Brenda K; White, Trevor; Witherington, Jason; Worby, Angela; Medhurst, Andrew D

2013-12-15

This Letter describes the discovery of a novel series of H3 receptor antagonists. The initial medicinal chemistry strategy focused on deconstructing and simplifying an early screening hit which rapidly led to the discovery of a novel series of H3 receptor antagonists based on the benzazepine core. Employing an H3 driven pharmacodynamic model, the series was then further optimised through to a lead compound that showed robust in vivo functional activity and possessed overall excellent developability properties. Copyright © 2013 Elsevier Ltd. All rights reserved.

Involvement of histamine H1 and H2 receptors in hypothermia induced by ionizing radiation in guinea pigs

International Nuclear Information System (INIS)

Kandasamy, S.B.; Hunt, W.A.

1988-01-01

Radiation-induced hypothermia was examined in guinea pigs. Exposure to the head alone or whole-body irradiation induced hypothermia, whereas exposure of the body alone produced a small insignificant response. Systemic injection of disodium cromoglycate (a mast cell stabilizer) and cimetidine (H2-receptor antagonist) had no effect on radiation-induced hypothermia, whereas systemic and central administration of mepyramine (H1-receptor antagonist) or central administration of disodium cromoglycate or cimetidine attenuated it, indicating the involvement of central histamine through both H1 and H2 receptors in this response. Serotonin is not involved, since the serotonin antagonist methysergide had no effect on radiation-induced hypothermia. These results indicate that central histaminergic systems may be involved in radiation-induced hypothermia. 34 references, 5 figures, 2 tables

Radioenzymatic assay for measurement of tissue concentrations of histamine: adaptation to correct for adherence of histamine to mechanical homogenizers

International Nuclear Information System (INIS)

Brown, J.K.; Frey, M.J.; Reed, B.R.; Leff, A.R.; Shields, R.; Gold, W.M.

1984-01-01

Because adherence of histamine to glass is well-known, we tested for its adherence to a mechanical homogenizer commonly used in the extraction of histamine from tissue samples. During 60 sec of homogenization, 15% to 17% of the histamine originally present in the samples ''disappeared,'' and the reason for the disappearance was reversible binding of histamine to the homogenizer. Adding trace amounts of [ 14 C]histamine to each sample before homogenization and measuring the disappearance of radioactivity during homogenization permitted correction for binding to the homogenizer. This technique for correction was validated by the measurement of endogenous concentrations of histamine in the tracheal posterior membranes of six dogs (range of mean concentrations: 0.63 to 1.51 ng/mg wet weight) followed by the measurement of known amounts of exogenous histamine added before homogenization to tracheal tissue samples from the same dogs. In the latter samples, 96 +/- 13% (mean +/- SEM) of the histamine added was measured by our technique. We conclude that binding of histamine to mechanical homogenizers may be an important cause of inaccuracy of the enzymatic assay for the measurement of histamine concentrations in tissue but that such binding may but that such binding may be easily corrected for

Sickle erythrocytes enhance phenylephrine and histamine ...

African Journals Online (AJOL)

Sickle erythrocytes enhance phenylephrine and histamine contractions of isolated rabbit carotid arteries. ... enhancement of histamine contractions, compared with phenylephrine (in AS and SS), suggests a possible role for histamine in the increased vascular tone and vaso-occlusive crisis in sickle cell disease.

The histamine content of dried flying fish products in Taiwan and the isolation of halotolerant histamine-forming bacteria.

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Kung, Hsien-Feng; Huang, Chun-Yung; Lin, Chia-Min; Liaw, Lon-Hsiu; Lee, Yi-Chen; Tsai, Yung-Hsiang

2015-06-01

Thirty dried flying fish products were purchased from fishing village stores in Taiwan and tested to detect the presence of histamine and histamine-forming bacteria. Except for histamine and cadaverine, the average content of various biogenic amines in the tested samples was less than 3.5 mg/100 g. Eight (26.6%) dried flying fish samples had histamine levels greater than the United States Food and Drug Administration guideline of 5 mg/100 g for scombroid fish and/or scombroid products, whereas four (13.3%) samples contained more than the hazard action level of 50 mg/100 g. One histamine-producing bacterial isolate was identified as Staphylococcus xylosus by 16S rDNA sequencing with polymerase chain reaction amplification. This isolate was capable of producing 507.8 ppm of histamine in trypticase soy broth supplemented with 1.0% l-histidine (TSBH). The S. xylosus isolate was a halotolerant bacterium that had a consistent ability to produce more than 300 ppm of histamine at 3% sodium chloride concentration in TSBH medium after 72 hours. Copyright © 2015. Published by Elsevier B.V.

The histamine content of dried flying fish products in Taiwan and the isolation of halotolerant histamine-forming bacteria

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Hsien-Feng Kung

2015-06-01

Full Text Available Thirty dried flying fish products were purchased from fishing village stores in Taiwan and tested to detect the presence of histamine and histamine-forming bacteria. Except for histamine and cadaverine, the average content of various biogenic amines in the tested samples was less than 3.5 mg/100 g. Eight (26.6% dried flying fish samples had histamine levels greater than the United States Food and Drug Administration guideline of 5 mg/100 g for scombroid fish and/or scombroid products, whereas four (13.3% samples contained more than the hazard action level of 50 mg/100 g. One histamine-producing bacterial isolate was identified as Staphylococcus xylosus by 16S rDNA sequencing with polymerase chain reaction amplification. This isolate was capable of producing 507.8 ppm of histamine in trypticase soy broth supplemented with 1.0% l-histidine (TSBH. The S. xylosus isolate was a halotolerant bacterium that had a consistent ability to produce more than 300 ppm of histamine at 3% sodium chloride concentration in TSBH medium after 72 hours.

Symptoms of pseudoallergy and histamine metabolism disorders

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Joanna Kacik

2016-09-01

Full Text Available Histamine intolerance is a poorly investigated type of hypersensitivity responsible for a number of often serious symptoms, erroneously interpreted as food allergy. Endogenous histamine originates from the histidine amino acid with the help of the histidine decarboxylase enzyme. Apart from the endogenous production histamine may be supplied to the body with food. Slow-maturing and fermenting products are characterised by particularly high levels of histamine. Some food products stimulate excessive release of histamine from stores in the body as well as containing significant amounts of it. These products include spices, herbs, dried fruits and a large group of food additives. Histamine intolerance is considered to be a condition in which the amount of histamine in the body exceeds its tolerance threshold, which leads to the development of adverse reactions. These reactions primarily include skin symptoms (pruritus, urticaria, skin reddening, acne lesions, angioedema, respiratory symptoms (nasal obstruction and watery discharge, sneezing, coughing, wheezing, gastrointestinal symptoms (abdominal cramps, diarrhoea, bloating, nervous system symptoms (headaches, fatigue, irritability, anxiety, panic attacks, cardiovascular symptoms (tachycardia, hypotension, chest pain, primary dysmenorrhoea and many more. It is estimated that nearly 1% of society is susceptible to histamine intolerance. The diagnosis of this disorder is based on observing at least two characteristic symptoms and their disappearance or improvement following histamine-free diet. A new, although not easily accessible diagnostic tool is assay for serum diamine oxidase activity, which correlates to a significant extent with symptoms of histamine intolerance. Normal activity of diamine oxidase is considered to be the amount of >80 HDU/mL, decreased activity – 40–80 HDU/mL and severely decreased activity – <40 HDU/mL. Currently the option of diamine oxidase supplementation is

Histamine acting on H1 receptor promotes inhibition of proliferation via PLC, RAC, and JNK-dependent pathways

International Nuclear Information System (INIS)

Notcovich, Cintia; Diez, Federico; Tubio, Maria Rosario; Baldi, Alberto; Kazanietz, Marcelo G.; Davio, Carlos; Shayo, Carina

2010-01-01

It is well established that histamine modulates cell proliferation through the activation of the histamine H1 receptor (H1R), a G protein-coupled receptor (GPCR) that is known to couple to phospholipase C (PLC) activation via Gq. In the present study, we aimed to determine whether H1R activation modulates Rho GTPases, well-known effectors of Gq/G 11 -coupled receptors, and whether such modulation influences cell proliferation. Experiments were carried out in CHO cells stably expressing H1R (CHO-H1R). By using pull-down assays, we found that both histamine and a selective H1R agonist activated Rac and RhoA in a time- and dose-dependent manner without significant changes in the activation of Cdc42. Histamine response was abolished by the H1R antagonist mepyramine, RGS2 and the PLC inhibitor U73122, suggesting that Rac and RhoA activation is mediated by H1R via Gq coupling to PLC stimulation. Histamine caused a marked activation of serum response factor activity via the H1R, as determined with a serum-responsive element (SRE) luciferase reporter, and this response was inhibited by RhoA inactivation with C3 toxin. Histamine also caused a significant activation of JNK which was inhibited by expression of the Rac-GAP β2-chimaerin. On the other hand, H1R-induced ERK1/2 activation was inhibited by U73122 but not affected by C3 or β2-chimaerin, suggesting that ERK1/2 activation was dependent on PLC and independent of RhoA or Rac. [ 3 H]-Thymidine incorporation assays showed that both histamine and the H1R agonist inhibited cell proliferation in a dose-dependent manner and that the effect was independent of RhoA but partially dependent on JNK and Rac. Our results reveal that functional coupling of the H1R to Gq-PLC leads to the activation of RhoA and Rac small GTPases and suggest distinct roles for Rho GTPases in the control of cell proliferation by histamine.

Albizia lebbeck suppresses histamine signaling by the inhibition of histamine H1 receptor and histidine decarboxylase gene transcriptions.

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Nurul, Islam Mohammed; Mizuguchi, Hiroyuki; Shahriar, Masum; Venkatesh, Pichairajan; Maeyama, Kazutaka; Mukherjee, Pulok K; Hattori, Masashi; Choudhuri, Mohamed Sahabuddin Kabir; Takeda, Noriaki; Fukui, Hiroyuki

2011-11-01

Histamine plays major roles in allergic diseases and its action is mediated mainly by histamine H(1) receptor (H1R). We have demonstrated that histamine signaling-related H1R and histidine decarboxylase (HDC) genes are allergic diseases sensitive genes and their expression level affects severity of the allergic symptoms. Therefore, compounds that suppress histamine signaling should be promising candidates as anti-allergic drugs. Here, we investigated the effect of the extract from the bark of Albizia lebbeck (AL), one of the ingredients of Ayruvedic medicines, on H1R and HDC gene expression using toluene-2,4-diisocyanate (TDI) sensitized allergy model rats and HeLa cells expressing endogenous H1R. Administration of the AL extract significantly decreased the numbers of sneezing and nasal rubbing. Pretreatment with the AL extract suppressed TDI-induced H1R and HDC mRNA elevations as well as [(3)H]mepyramine binding, HDC activity, and histamine content in the nasal mucosa. AL extract also suppressed TDI-induced up-regulation of IL-4, IL-5, and IL-13 mRNA. In HeLa cells, AL extract suppressed phorbol-12-myristate-13-acetate- or histamine-induced up-regulation of H1R mRNA. Our data suggest that AL alleviated nasal symptoms by inhibiting histamine signaling in TDI-sensitized rats through suppression of H1R and HDC gene transcriptions. Suppression of Th2-cytokine signaling by AL also suggests that it could affect the histamine-cytokine network. Copyright © 2011 Elsevier B.V. All rights reserved.

Effect of crude methanol leaf extract of Combretum racemosum on histamine-stimulated gastric secretion in rats

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Chukwugozie Nwachukwu Okwuosa

2017-02-01

Full Text Available Objective: To investigate the effect of crude methanolic extract of Combretum racemosum (C. racemosum leaves on histamine-stimulated gastric secretion in rats. Methods: Phytochemical and acute toxicity tests were performed. Anti-secretory activity of C. racemosum extract was investigated in pyloric ligated rats administered histamine. Gastric juice was collected from all the animals and the volume, titratable acidity, pH and mucus content were measured. The effect of C. racemosum extract on calcium chloride induced contractions of the guinea-pig ileum suspended in high potassium, calcium-deficient depolarizing solution was investigated. The H2 receptor antagonistic potency was also evaluated using the isolated non-gravid rat uterus. Results: Phytochemistry revealed the presence of abundant amounts of saponins and moderate amounts of glycosides, terpenoids, proteins, reducing sugar, resins, alkaloids, flavonoids and carbohydrates. The oral LD50 of the extract was greater than 8 000 mg/kg body weight in mice. Pretreatment of pyloric ligated rats with C. racemosum prior to histamine administration significantly reduced (P < 0.001 the volume of gastric juice and titratable acidity, and significantly increased (P < 0.001 gastric pH and gastric mucus when compared to the negative control. Both doses of C. racemosum protected rats significantly (P < 0.001 from histamine-induced ulceration. C. racemosum potently inhibited contractions evoked by calcium chloride in a dose-dependent and reversible manner with an IC50 of 1 132 µg/mL. It also antagonized the relaxant effect of histamine on the isolated rat uterus in a manner comparable to cimetidine. Conclusions: The leaves of C. racemosum possess gastric anti-secretory and anti-ulcer effects and justify its use in traditional medicine in South-East Nigeria for the treatment of peptic ulcer disease.

PPI versus Histamine H2 Receptor Antagonists for Prevention of Upper Gastrointestinal Injury Associated with Low-Dose Aspirin: Systematic Review and Meta-analysis.

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Chen Mo

Full Text Available This study compared proton pump inhibitors (PPIs and histamine H2 receptor antagonists (H2RAs for prevention of low-dose aspirin (LDA-related gastrointestinal (GI erosion, ulcer and bleeding. Electronic databases including PubMed, Embase, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, and WanFang Data were searched from the date of their establishment to December 31, 2013. Randomized controlled trials comparing PPIs and H2RAs for prevention of GI injury associated with low-dose aspirin (LDA were collected. Two reviewers independently abstracted studies and patient characteristics and appraised study quality using the Cochrane risk-of-bias tool. Meta-analysis was performed using RevMan 5.1 software. We included nine RCTs involving 1047 patients. The meta-analysis showed that PPIs were superior to H2RAs for prevention of LDA-associated GI erosion/ulcer [odds ratio (OR=0.28, 95% confidence interval (CI: 0.16-0.50] and bleeding (OR=0.28, 95% CI: 0.14-0.59. In conclusion, PPIs were superior to H2RAs for prevention of LDA-related GI erosion/ulcer and bleeding. Higher quality, large, multicenter RCTs are needed to demonstrate the preventive effect of the two acid-suppressive drugs.

Degradation of Histamine by Lactobacillus plantarum Isolated from Miso Products.

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Kung, Hsien-Feng; Lee, Yi-Chen; Huang, Ya-Ling; Huang, Yu-Ru; Su, Yi-Cheng; Tsai, Yung-Hsiang

2017-10-01

Histamine is a toxic chemical and is the causative agent of food poisoning. This foodborne toxin may be degraded by the oxidative deamination activity of certain microorganisms. In this study, we isolated four histamine-degrading Lactobacillus plantarum bacteria from miso products. Among them, L. plantarum D-103 exhibited 100% degradation of histamine in de Man Rogosa Sharpe (MRS) broth containing 50 ppm of histamine after 24 h of incubation at 30°C. The optimal growth, histamine oxidase, and histamine-degrading activity of L. plantarum D-103 were observed in histamine MRS broth at pH 7.0, 3% NaCl, and 30°C. It also exhibited tolerance to broad ranges of pH (4 to 10) and salt concentrations (0 to 12%) in histamine MRS broth. Therefore, the histamine-degrading L. plantarum D-103 might be used as an additive culture to prevent histamine accumulation in miso products during fermentation.

3H-histamine release from human leukocytes

International Nuclear Information System (INIS)

Stahl Skov, P.; Norn, S.; Weeke, B.

1979-01-01

A rapid, simple, and inexpensive method for large scale screening of patients suspected of type I allergy has been developed. The method is based on in vitro incorporation of 3 H-histamine in the leukocytes of the patient, whereafter release of labelled histamine is measured after provocation of the cells with the suspected allergen. The new method was compared with the conventional basophil histamine release technique by in vitro provocation of six asthmatic patients under suspicion of type I allergy against animal dander, house dust, and mite, and an almost identical release of histamine was observed in both assays. (author)

Circadian profiling reveals higher histamine plasma levels and lower diamine oxidase serum activities in 24% of patients with suspected histamine intolerance compared to food allergy and controls.

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Pinzer, T C; Tietz, E; Waldmann, E; Schink, M; Neurath, M F; Zopf, Y

2018-04-01

Histamine intolerance is thought to trigger manifold clinical symptoms after ingesting histamine-rich food due to reduced activity of diamine oxidase (DAO). No study has hitherto systematically assessed daily fluctuations of histamine levels and DAO activities in symptomatic patients. The aim of the study was to investigate the presence of histamine intolerance, to therefore establish day profiles of histamine levels and DAO activities, and to compare the results between patients with suspected histamine intolerance, food allergy and healthy controls. We determined day profiles of histamine plasma levels and DAO serum activities in 33 patients with suspected histamine intolerance, in 21 patients with proven food allergy and in 10 healthy control patients. Clinical symptoms, food intolerances and further clinical and laboratory chemical parameters were evaluated. Twenty-four percent (8 of 33) suspected histamine-intolerant patients showed elevated histamine levels during the day. That might be caused by constantly and significantly reduced DAO activities in these patients compared to food-allergic and control patients. The remaining 25 patients presented normal histamine levels and DAO activities, but an increased prevalence of multiple food intolerances compared to the other subgroup of suspected histamine-intolerants. There was no correlation between subjective complaints and serological histamine parameters in patients with suspected histamine intolerance. We determined by daily profiling that decreased DAO activities correlated with elevated histamine levels in a subgroup of suspected histamine-intolerants. This finding discriminates these patients from food intolerant individuals with similar clinical symptoms and strongly suggests the presence of histamine intolerance. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

OCCURANCE OF HISTAMINE IN FISH PRODUCTS ON MARKET

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R. Mancusi

2012-08-01

Full Text Available Histamine fish poisoning is quite common and occur in consequence of microbial decarboxylase whose activity begin early in the post-mortem but are triggered in consequence of abuse in the shelf life of fish products. In this study forty-eight samples of tuna, mackerel, anchovies, sardines, fresh or processed were sampled from fish shops and supermarkets in the City of Bologna in the period from January to July 2010. Concentration of histamine was assessed using ELISA quantitative test and presence of psicrotrophic histamine forming bacteria was searched using a modified Niven agar medium which allow detection of suspect colonies that were confirmed by PCR for detecting the presence of the histidine decarboxylase genes in their DNA. The positive colonies were then identified on the basis of their morphology, Gram reaction and biochemical characteristics with API20E. The differential capability of the Niven agar was found to be low and approximately one fifth of the suspect colonies were confirmed by the PCR test, which however included both strong and weak histamine producing strains. The presence of Morganella morganii was associated with concentration of histamine 460 mg∙kg-1 above the allowed limit in a sample of tuna sampled from a fish shop. The same bacterium was found in samples of Atlantic horse mackerel (Trachurus trachurus. High histamine concentration (between 258 and > 300 mg∙kg-1 were observed in salted European pilchard and European anchovy (228 mg∙kg-1 sold loose in supermarkets. Because temperature abuse could occur when Tuna (fresh/defrozen are hold on chopping board to sell fresh cuts and during shelf life of salted pilchard and pickled anchovies held in opened cans in chilled display cabinets for extended period, which might results in very high histamine concentration, controls on time and temperature at the retail, in addition to those done during the harvest and processing are needed. The studies aiming at

Histamine and Antihistamines / Histamin i antihistamini

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Stojković Nikola

2015-03-01

Full Text Available Poslednjih godina beleži se kontinuirani rast prevalencije alergijskih oboljenja. Alergijski imunski odgovor predstavlja jednu kompleksnu mrežu ćelijskih događaja u kojoj učestvuju mnogobrojne imunske ćelije i medijatori. On predstavlja interakciju urođenog i stečenog imunskog odgovora. Ključnu ulogu u imunološkoj kaskadi zauzima histamin, prirodni sastojak tela, koga u alergijskom inflamatornom odgovoru oslobađaju mastociti i bazofili. Cilj ovog rada bio je naglasiti ulogu histamina u alergijskim imunološkim događajima, njegov efekat na Th1 i Th2 subpopulaciju limfocita i produkciju odgovarajućih citokina, kao i ulogu blokatora histamina u tretmanu ovih stanja. Histamin ostvaruje svoj efekat vezivanjem za četiri tipa svojih receptora koji su široko distribuirani u organizmu. Blokatori histamina blokiraju mnogobrojne efekte histamina vezivanjem za ove receptore. Cetirizin, visoko selektivni antihistaminik druge generacije, ne ostvaruje svoje efekte samo vezivanjem za H1 receptore već dovodi do atenuisanja mnogobrojnih zbivanja tokom inflamacijskog procesa. Dobro poznavanje efekata histaminskih blokatora, među njima i cetirizina, može dovesti do pravog odabira terapije u tretmanu alergijskih oboljenja.

Serum diamine oxidase activity in patients with histamine intolerance.

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Manzotti, G; Breda, D; Di Gioacchino, M; Burastero, S E

2016-03-01

Intolerance to various foods, excluding bona fide coeliac disease and lactose intolerance, represents a growing cause of patient visits to allergy clinics.Histamine intolerance is a long-known, multifaceted clinical condition triggered by histamine-rich foods and alcohol and/or by drugs that liberate histamine or block diamine oxidase (DAO), the main enzyme involved in the metabolism of ingested histamine. Histamine limitation diets impose complex, non-standardized restrictions that may severely impact the quality of life of patients. We retrospectively evaluated 14 patients who visited allergy outpatient facilities in northern Italy with a negative diagnosis for IgE-mediated food hypersensitivity, coeliac disease, conditions related to gastric hypersecretion, and systemic nickel hypersensitivity, and who previously underwent a histamine limitation diet with benefits for their main symptoms. Serum diamine oxidase levels and the clinical response to diamine oxidase supplementation were investigated. We found that 10 out of 14 patients had serum DAO activityintolerance. Moreover, 13 out of 14 patients subjectively reported a benefit in at least one of the disturbances related to food intolerances following diamine oxidase supplementation. The mean value (±SD) of diamine oxidase activity in the cohort of patients with histamine intolerance symptoms was 7.04±6.90 U/mL compared to 39.50±18.16 U/mL in 34 healthy controls (P=0.0031). In patients with symptoms triggered by histamine-rich food, measuring the serum diamine oxidase activity can help identify subjects who can benefit from a histamine limitation diet and/or diamine oxidase supplementation.Properly designed, controlled studies investigating histamine intolerance that include histamine provocation are indispensable for providing insights into the area of food intolerances, which are currently primarily managed with non-scientific approaches in Italy. © The Author(s) 2015.

In Vivo Histamine Optical Nanosensors

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Heather A. Clark

2012-08-01

Full Text Available In this communication we discuss the development of ionophore based nanosensors for the detection and monitoring of histamine levels in vivo. This approach is based on the use of an amine-reactive, broad spectrum ionophore which is capable of recognizing and binding to histamine. We pair this ionophore with our already established nanosensor platform, and demonstrate in vitro and in vivo monitoring of histamine levels. This approach enables capturing rapid kinetics of histamine after injection, which are more difficult to measure with standard approaches such as blood sampling, especially on small research models. The coupling together of in vivo nanosensors with ionophores such as nonactin provide a way to generate nanosensors for novel targets without the difficult process of designing and synthesizing novel ionophores.

The Histamine H1 Receptor Participates in the Increased Dorsal Telencephalic Neurogenesis in Embryos from Diabetic Rats

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Karina H. Solís

2017-12-01

Full Text Available Increased neuron telencephalic differentiation during deep cortical layer formation has been reported in embryos from diabetic mice. Transitory histaminergic neurons within the mesencephalon/rhombencephalon are responsible for fetal histamine synthesis during development, fibers from this system arrives to the frontal and parietal cortex at embryo day (E 15. Histamine is a neurogenic factor for cortical neural stem cells in vitro through H1 receptor (H1R which is highly expressed during corticogenesis in rats and mice. Furthermore, in utero administration of an H1R antagonist, chlorpheniramine, decreases the neuron markers microtubuline associated protein 2 (MAP2 and forkhead box protein 2. Interestingly, in the diabetic mouse model of diabetes induced with streptozotocin, an increase in fetal neurogenesis in terms of MAP2 expression in the telencephalon is reported at E11.5. Because of the reported effects on cortical neuron differentiation of maternal diabetes in one hand and of histamine in the other, here the participation of histamine and H1R on the increased dorsal telencephalic neurogenesis was explored. First, the increased neurogenesis in the dorsal telencephalon at E14 in diabetic rats was corroborated by immunohistochemistry and Western blot. Then, changes during corticogenesis in the level of histamine was analyzed by ELISA and in H1R expression by qRT-PCR and Western blot and, finally, we tested H1R participation in the increased dorsal telencephalic neurogenesis by the systemic administration of chlorpheniramine. Our results showed a significant increase of histamine at E14 and in the expression of the receptor at E12. The administration of chlorpheniramine to diabetic rats at E12 prevented the increased expression of βIII-tubulin and MAP2 mRNAs (neuron markers and partially reverted the increased level of MAP2 protein at E14, concluding that H1R have an important role in the increased neurogenesis within the dorsal telencephalon

Histamine (Scombroid) Fish Poisoning: a Comprehensive Review.

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Feng, Charles; Teuber, Suzanne; Gershwin, M Eric

2016-02-01

Histamine fish poisoning, also known as scombroid poisoning, is the most common cause of ichythyotoxicosis worldwide and results from the ingestion of histamine-contaminated fish in the Scombroidae and Scomberesocidae families, including mackerel, bonito, albacore, and skipjack. This disease was first described in 1799 in Britain and re-emerged in the medical literature in the 1950s when outbreaks were reported in Japan. The symptoms associated with histamine fish poisoning are similar to that of an allergic reaction. In fact, such histamine-induced reactions are often misdiagnosed as IgE-mediated fish allergy. Indeed, histamine fish poisoning is still an underrecognized disease. In this review, we discuss the epidemiology, pathophysiology, evaluation, and treatment of scombroid disease. Because more than 80% of fish consumed in the USA is now imported from other countries, the disease is intimately linked with the global fish trade (National Marine Fisheries Service, 2012). Preventing future scombroid outbreaks will require that fishermen, public health officials, restaurant workers, and medical professionals work together to devise international safety standards and increase awareness of the disease. The implications of scombroid poisoning go far beyond that of fish and have broader implications for the important issues of food safety.

The role of cortical and hypothalamic histamine-3 receptors in the modulation of central histamine neurotransmission : an in vivo electrophysiology and microdialysis study

NARCIS (Netherlands)

Flik, Gunnar; Dremencov, Eliyahu; Cremers, Thomas I. H. F.; Folgering, Joost H. A.; Westerink, Ben H. C.

2011-01-01

The current study aimed to investigate the effect of histamine-3 (H3) receptors, expressed in the tuberomammillary nucleus (TMN) of the hypothalamus and in the prefrontal cortex (PFC), on histamine neurotransmission in the rat brain. The firing activity of histamine neurons in the TMN was measured

Histamine formation in flying fish contaminated with Staphylococcus xylosus

Directory of Open Access Journals (Sweden)

Hsien-Feng Kung

2016-06-01

Full Text Available Abstract Histamine is the main causative agent of scombroid poisoning. However, unlike scombroid fish, histamine poisoning due to consumption of flying fish has never been reported. In this study, the white muscle of flying fish had high levels of free histidine at approximately 423.9 mg/100 g, and was inoculated with Staphylococcus xylosus Q2 isolated from dried flying fish at 5.0 log CFU/g and stored at −20 to 35°C to investigate histamine-related quality. The histamine contents quickly increased to higher than 50 mg/100 g in samples stored at 25 and 35°C within 12 h as well as stored at 15°C within 48 h. However, bacterial growth and histamine formation were controlled by cold storage of the samples at 4°C or below. Once the frozen flying fish samples stored at −20°C for 2 months were thawed and stored at 25°C after 24 h, histamine started to accumulate rapidly (>50 mg/100 g of fish. Therefore, flying fish muscle was a good substrate for histamine formation by bacterial histidine decarboxylation at elevated temperatures (>15°C when it is contaminated with S. xylosus. In conclusion, since the improperly contaminated flying fish muscle with S. xylosus could lead to production of hazardous levels of histamine over time when stored at temperatures >15°C, the flying fish should be stored below 4 °C or below to control proliferation of S. xylosus, and TVBN and histamine production.

Anticonvulsant and reproductive toxicological studies of the imidazole-based histamine H3R antagonist 2-18 in mice

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Bastaki SM

2018-01-01

Full Text Available Salim M Bastaki,1 Yousef M Abdulrazzaq,2 Mohamed Shafiullah,1 Małgorzata Więcek,3 Katarzyna Kieć-Kononowicz,3 Bassem Sadek1 1Department of Pharmacology and Therapeutics, College of Medicine and Health Science, United Arab Emirates University, Al Ain, 2Department of Medical Education, Dubai Health Authority, Dubai, UAE; 3Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna, Kraków, Poland Abstract: The imidazole-based H3R antagonist 2-18 with high in vitro H3R antagonist affinity, excellent in vitro selectivity profile, and high in vivo H3R antagonist potency was tested for its anticonvulsant effect in maximal electroshock (MES-induced convulsions in mice having valproic acid (VPA as a reference antiepileptic drug (AED. Additionally, H3R antagonist 2-18 was evaluated for its reproductive toxicity in the same animal species. The results show that acute systemic administration (intraperitoneal; i.p. of H3R antagonist 2-18 (7.5, 15, 30, and 60 mg/kg, i.p. significantly and dose dependently protected male as well as female mice against MES-induced convulsion. The protective action observed for H3R antagonist 2-18 in both mice sexes was comparable to that of VPA and was reversed when mice were pretreated with the selective H3R agonist (R-alpha-methylhistamine (RAMH, 10 mg/kg, i.p.. Moreover, the results show that acute systemic administration of single (7.5, 15, 30, or 60 mg/kg, i.p. or multiple doses (15×3 mg/kg, i.p. of H3R antagonist 2-18 on gestation day (GD 8 or 13 did not affect the maternal body weight of mice when compared with the control group. Furthermore, no significant differences were observed in the average number of implantations and resorptions between the control and H3R antagonist 2-18-treated group at the early stages of gestation and the organogenesis period. However, oral treatment with H3R antagonist 2-18 (15 mg/kg on GD 8 induced a reduced number of

Comparative influence of propranolol and verapamil on glycemic control and histamine sensitivity associated with L-thyroxine-induced hyperthyroidism - an experimental study.

Science.gov (United States)

Bhatt, Parloop A; Makwana, Dharmesh

2008-02-01

The present investigation was undertaken to study the comparative effectiveness of beta-adrenergic antagonist propranolol and calcium channel blocker verapamil on L-thyroxine-induced alteration on glycemic control and histamine sensitivity on rats and guinea pigs, respectively. Injection of L-thyroxine sodium every alternate day for 3 weeks in guinea pigs (75 microg/kg, i.p.) and rats (75 mg/kg, s.c.) produced a condition similar to thyrotoxicosis. Verapamil and propranolol administered daily in the third week along with L-thyroxine to two separate groups of hyperthyroid animals reversed thyroxine-induced loss in body weight, reduction in serum TSH levels, and rise in body temperature. Effect on glucose metabolism and insulin sensitivity was studied on rats. Compared to normal rats, L-thyroxine-treated animals showed a state of hyperglycemia, hyperinsulinemia, impaired glucose tolerance, and insulin resistance. Propranolol (10 mg/kg, i.p.) treatment significantly decreased fasting serum glucose levels without affecting serum insulin levels, AUC glucose, and K(ITT) values. Treatment with verapamil (5 mg/kg, i.p.) significantly reduced fasting serum glucose and insulin levels, AUC glucose, and significantly increased K(ITT) values. Effect of propranolol (15 mg/kg, orally) and verapamil (20 mg/kg, orally) treatment on histamine sensitivity was studied on L-thyroxine-treated guinea pigs. Compared to normal guinea pigs, L-thyroxine-treated guinea pigs showed an increased sensitivity to histamine-induced asphyxia. Verapamil treatment reversed this increased histamine sensitivity while propranolol aggravated it. In conclusion, compared to propranolol, verapamil has advantageous effects on glucose metabolism, insulin and histamine sensitivity and could therefore be a valuable addition as an adjunctive therapy option currently available for thyrotoxicosis associated with diabetes and/or anaphylaxis.

Effect of acute aerobic exercise and histamine receptor blockade on arterial stiffness in African Americans and Caucasians.

Science.gov (United States)

Yan, Huimin; Ranadive, Sushant M; Lane-Cordova, Abbi D; Kappus, Rebecca M; Behun, Michael A; Cook, Marc D; Woods, Jeffrey A; Wilund, Kenneth R; Baynard, Tracy; Halliwill, John R; Fernhall, Bo

2017-02-01

African Americans (AA) exhibit exaggerated central blood pressure (BP) and arterial stiffness measured by pulse wave velocity (PWV) in response to an acute bout of maximal exercise compared with Caucasians (CA). However, whether potential racial differences exist in central BP, elastic, or muscular arterial distensibility after submaximal aerobic exercise remains unknown. Histamine receptor activation mediates sustained postexercise hyperemia in CA but the effect on arterial stiffness is unknown. This study sought to determine the effects of an acute bout of aerobic exercise on central BP and arterial stiffness and the role of histamine receptors, in AA and CA. Forty-nine (22 AA, 27 CA) young and healthy subjects completed the study. Subjects were randomly assigned to take either histamine receptor antagonist or control placebo. Central blood BP and arterial stiffness measurements were obtained at baseline, and at 30, 60, and 90 min after 45 min of moderate treadmill exercise. AA exhibited greater central diastolic BP, elevated brachial PWV, and local carotid arterial stiffness after an acute bout of submaximal exercise compared with CA, which may contribute to their higher risk of cardiovascular disease. Unexpectedly, histamine receptor blockade did not affect central BP or PWV in AA or CA after exercise, but it may play a role in mediating local carotid arterial stiffness. Furthermore, histamine may mediate postexercise carotid arterial dilation in CA but not in AA. These observations provide evidence that young and healthy AA exhibit an exaggerated hemodynamic response to exercise and attenuated vasodilator response compared with CA. NEW & NOTEWORTHY African Americans are at greater risk for developing cardiovascular disease than Caucasians. We are the first to show that young and healthy African Americans exhibit greater central blood pressure, elevated brachial stiffness, and local carotid arterial stiffness following an acute bout of submaximal exercise

Involvement of the histamine H4 receptor in clozapine-induced hematopoietic toxicity: Vulnerability under granulocytic differentiation of HL-60 cells

International Nuclear Information System (INIS)

Goto, Aya; Mouri, Akihiro; Nagai, Tomoko; Yoshimi, Akira; Ukigai, Mako; Tsubai, Tomomi; Hida, Hirotake; Ozaki, Norio; Noda, Yukihiro

2016-01-01

Clozapine is an effective antipsychotic for treatment-resistant schizophrenia, but can cause fatal hematopoietic toxicity as agranulocytosis. To elucidate the mechanism of hematopoietic toxicity induced by clozapine, we developed an in vitro assay system using HL-60 cells, and investigated the effect on hematopoiesis. HL-60 cells were differentiated by all-trans retinoic acid (ATRA) into three states according to the following hematopoietic process: undifferentiated HL-60 cells, those undergoing granulocytic ATRA-differentiation, and ATRA-differentiated granulocytic cells. Hematopoietic toxicity was evaluated by analyzing cell survival, cell proliferation, granulocytic differentiation, apoptosis, and necrosis. In undifferentiated HL-60 cells and ATRA-differentiated granulocytic cells, both clozapine (50 and 100 μM) and doxorubicin (0.2 µM) decreased the cell survival rate, but olanzapine (1–100 µM) did not. Under granulocytic differentiation for 5 days, clozapine, even at a concentration of 25 μM, decreased survival without affecting granulocytic differentiation, increased caspase activity, and caused apoptosis rather than necrosis. Histamine H 4 receptor mRNA was expressed in HL-60 cells, whereas the expression decreased under granulocytic ATRA-differentiation little by little. Both thioperamide, a histamine H 4 receptor antagonist, and DEVD-FMK, a caspase-3 inhibitor, exerted protection against clozapine-induced survival rate reduction, but not of live cell counts. 4-Methylhistamine, a histamine H 4 receptor agonist, decreased the survival rate and live cell counts, as did clozapine. HL-60 cells under granulocytic differentiation are vulnerable under in vitro assay conditions to hematopoietic toxicity induced by clozapine. Histamine H 4 receptor is involved in the development of clozapine-induced hematopoietic toxicity through apoptosis, and may be a potential target for preventing its occurrence through granulocytic differentiation. - Highlights: • HL-60

Blood histamine release: A new allergy blood test

International Nuclear Information System (INIS)

Faraj, B.A.; Gottlieb, G.R.; Camp, V.M.; Lollies, P.

1985-01-01

Allergen-mediated histamine release from human leukocytes represents an important model for in vitro studies of allergic reactions. The purpose of this study was to determine whether the measurement of histamine released in allergic patients (pts) by radioenzymatic assay following mixing of their blood with common allergens represents a reliable index for diagnosis of atopic allergy. Three categories of allergies were used: (1) housedust and mite; (2) cat and dog dander; (3) trees and grasses and ragweed mixture. The presence of allergy was established by intradermal skin testing in the study group of 82 pts. Significant atopy was defined as ≥ 3+ (overall range 0-4 +, negative to maximum) on skin testing. The test was carried out in tubes with 0.5 ml heparinized blood, 0.5 ml tris albumin buffer, and one of the allergens (60-100 PNU/ml). In 20 controls without allergy, there always was ≤ 4% histamine release (normal response). A significant allergen-mediated histamine release, ranging from 12 to 30% of the total blood histamine content, was observed in 96% of the pts with skin test sensitivity of ≥ 3+. There was good agreement between skin testing and histamine release in terms of the allergen causing the response. Thus, measurement of histamine release in blood in response to allergen challenge represents a clinically useful in vitro test for the diagnosis of atopic allergy. Because data can be obtained from a single sample and are highly quantitative, this new method should have application to the longitudinal study of allergic pts and to the assessment of interventions

Characterization of cutaneous vascular permeability induced by platelet-activating factor in guinea pigs and rats and its inhibition by a platelet-activating factor receptor antagonist

International Nuclear Information System (INIS)

Hwang, S.B.; Li, C.L.; Lam, M.H.; Shen, T.Y.

1985-01-01

Mechanisms of platelet-activating factor (PAF)-induced increases of cutaneous vascular permeability in guinea pigs and in rats were further explored. PAF so far is the most potent vasoactive mediator, being more than 1000-fold more potent than histamine and bradykinin in both species. In guinea pigs, there is a time delay of 5 to 10 minutes before PAF action, whereas, in the rat, the increased vasopermeability occurs immediately following the intradermal PAF injection. Relative vasoactive potencies of PAF and several structure-related analogues in both species correlate very well with their relative inhibition of the binding of 3 H-PAF to specific receptor sites on isolated rabbit platelet plasma membranes and their aggregatory abilities of rabbit platelets. Furthermore, the PAF-induced cutaneous vascular permeability is inhibitable by a competitive specific PAF receptor antagonist, kadsurenone, suggesting that binding of PAF to its specific receptor site is the first step to initiate its action of increased cutaneous vascular permeability. Several pure cyclooxygenase inhibitors, including indomethacin, diflunisal, and flurbiprofen, and the dual cyclooxygenase/lipoxygenase inhibitor, BW755C, but not the histamine antagonists, inhibit the PAF-induced vasopermeability in guinea pigs. The inhibition by indomethacin or BW755C can be fully reversed by coinjection intradermally with PAF and prostaglandin E1 but not leukotriene B4. Also, prostaglandin E1 but not leukotriene B4 enhances the guinea pig in vivo response to PAF in this model. However, in rats, none of the cyclooxygenase inhibitors, histamine antagonists, or BW755C inhibit the PAF effect of cutaneous phenomena

Safety, tolerability and pharmacokinetics of the histamine H3 receptor antagonist, ABT-288, in healthy young adults and elderly volunteers.

Science.gov (United States)

Othman, Ahmed A; Haig, George; Florian, Hana; Locke, Charles; Zhang, Jun; Dutta, Sandeep

2013-05-01

The objective of this work was to characterize the safety, tolerability and pharmacokinetics of ABT-288, a highly selective histamine H3 receptor antagonist, in healthy young adults and elderly subjects following single and multiple dosing in a phase 1 setting. Single doses (0.1, 0.3, 1, 3, 10, 20 and 40 mg ABT-288) and multiple doses (0.5, 1.5, 3 and 6 mg ABT-288 once-daily for 14 days) were evaluated in young adults and multiple doses (0.5, 1.5, 3 and 5 mg ABT-288 once-daily for 12 days) were evaluated in elderly subjects using randomized, double-blind, placebo-controlled, dose-escalating study designs. The effect of food on ABT-288 pharmacokinetics (5 mg single dose) was evaluated using an open label, randomized, crossover design. ABT-288 safety, tolerability and pharmacokinetics were comparable in young and elderly subjects. Single doses up to 40 mg and multiple doses up to 3 mg once-daily were generally safe and well tolerated. The most frequently reported adverse events were hot flush, headache, abnormal dreams, insomnia, nausea and dizziness. ABT-288 exposure (AUC) was dose-proportional over the evaluated dose ranges. The mean elimination half-life ranged from 40 to 61 h across dose groups. Steady state was achieved by day 10 of once-daily dosing with 3.4- to 4.2-fold accumulation. Food did not have a clinically meaningful effect on ABT-288 exposure. Based on the above results, 1 and 3 mg once-daily doses of ABT-288 were advanced to phase 2 evaluation in Alzheimer's patients. © 2012 Abbott Laboratories. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

Influence of iodinated contrast media on the activities of histamine inactivating enzymes diamine oxidase and histamine N-methyltransferase in vitro.

Science.gov (United States)

Kuefner, M A; Feurle, J; Petersen, J; Uder, M; Schwelberger, H G

2014-01-01

Iodinated contrast media can cause pseudoallergic reactions associated with histamine release in significant numbers of patients. To clarify whether these adverse reactions may be aggravated by a compromised histamine catabolism we asked if radiographic contrast agents in vitro inhibit the histamine inactivating enzymes diamine oxidase (DAO) and histamine N-methyltransferase (HMT). Nine iodinated contrast agents were tested in vitro. Following pre-incubation of purified porcine kidney DAO and recombinant human HMT with 0.1-10mM of the respective contrast medium (H2O and specific inhibitors of DAO and HMT as controls) enzyme activities were determined by using radiometric micro assays. None of the contrast media irrespective of their structure showed significant inhibition of the activities of DAO and HMT. Pre-incubation of the enzymes with specific inhibitors led to complete inhibition of the respective enzymatic activity. The iodinated contrast media tested in vitro did not exhibit inhibition of histamine converting enzymes at physiologically relevant concentrations. However due to the in vitro character of this study these results do not directly reflect the in vivo situation. Copyright © 2012 SEICAP. Published by Elsevier Espana. All rights reserved.

Generation of cell lines for drug discovery through random activation of gene expression: application to the human histamine H3 receptor.

Science.gov (United States)

Song, J; Doucette, C; Hanniford, D; Hunady, K; Wang, N; Sherf, B; Harrington, J J; Brunden, K R; Stricker-Krongrad, A

2005-06-01

Target-based high-throughput screening (HTS) plays an integral role in drug discovery. The implementation of HTS assays generally requires high expression levels of the target protein, and this is typically accomplished using recombinant cDNA methodologies. However, the isolated gene sequences to many drug targets have intellectual property claims that restrict the ability to implement drug discovery programs. The present study describes the pharmacological characterization of the human histamine H3 receptor that was expressed using random activation of gene expression (RAGE), a technology that over-expresses proteins by up-regulating endogenous genes rather than introducing cDNA expression vectors into the cell. Saturation binding analysis using [125I]iodoproxyfan and RAGE-H3 membranes revealed a single class of binding sites with a K(D) value of 0.77 nM and a B(max) equal to 756 fmol/mg of protein. Competition binding studies showed that the rank order of potency for H3 agonists was N(alpha)-methylhistamine approximately (R)-alpha- methylhistamine > histamine and that the rank order of potency for H3 antagonists was clobenpropit > iodophenpropit > thioperamide. The same rank order of potency for H3 agonists and antagonists was observed in the functional assays as in the binding assays. The Fluorometic Imaging Plate Reader assays in RAGE-H3 cells gave high Z' values for agonist and antagonist screening, respectively. These results reveal that the human H3 receptor expressed with the RAGE technology is pharmacologically comparable to that expressed through recombinant methods. Moreover, the level of expression of the H3 receptor in the RAGE-H3 cells is suitable for HTS and secondary assays.

Human eosinophils - potential pharmacological model applied in human histamine H4 receptor research.

Science.gov (United States)

Grosicki, Marek; Kieć-Kononowicz, Katarzyna

2015-01-01

Histamine and histamine receptors are well known for their immunomodulatory role in inflammation. In this review we describe the role of histamine and histamine H4 receptor on human eosinophils. In the first part of article we provide short summary of histamine and histamine receptors role in physiology and histamine related therapeutics used in clinics. We briefly describe the human histamine receptor H4 and its ligands, as well as human eosinophils. In the second part of the review we provide detailed description of known histamine effects on eosinophils including: intracellular calcium concentration flux, actin polymerization, cellular shape change, upregulation of adhesion proteins and cellular chemotaxis. We provide proofs that these effects are mainly connected with the activation of histamine H4 receptor. When examining experimental data we discuss the controversial results and limitations of the studies performed on isolated eosinophils. In conclusion we believe that studies on histamine H4 receptor on human eosinophils can provide interesting new biomarkers that can be used in clinical studies of histamine receptors, that in future might result in the development of new strategies in the treatment of chronic inflammatory conditions like asthma or allergy, in which eosinophils are involved.

Challenges in Developing a Biochip for Intact Histamine Using Commercial Antibodies

Directory of Open Access Journals (Sweden)

Leena Mattsson

2017-12-01

Full Text Available This study describes the development and the challenges in the development of an on-chip immunoassay for histamine using commercially available antibodies. Histamine can be used as an indicator of food freshness and quality, but it is also a relevant marker in clinical diagnostics. Due to its low molecular weight, simple structure and thus low immunogenicity production of high specificity and affinity antibodies is difficult. From six commercial anti-histamine antibodies tested, only two bound the histamine free in the solution. A fluorescent on-chip immunoassay for histamine was established with a dynamic range of 8–111 µg/mL using polyclonal anti-histamine antibody H7403 from Sigma (Mendota Heights, MN, USA. The anti-histamine antibodies described and used in published literature are thoroughly reviewed and the quality of commercial antibodies and their traceability and quality issues are highlighted and extensively discussed.

Existence of carcinine, a histamine-related compound, in mammalian tissues

International Nuclear Information System (INIS)

Flancbaum, L.; Brotman, D.N.; Fitzpatrick, J.C.; Van Es, Theodorus; Kasziba, E.; Fisher, H.

1990-01-01

Carcinine (β-alanylhistamine) was synthesized in vitro from histamine and β-alanine. It was detected quantitatively using an HPLC method previously described for the quantification of the related compounds histamine, histidine, carnosine and 3-methylhistamine. Carcinine was identified in several tissues of the rat, guinea pig, mouse and human, and was then shown to be metabolically related in vivo to histamine, histidine, carnosine and 3-methylhistamine through radioisotopic labeling. The results demonstrate that carcinine may be concurrently quantitated using the same HPLC method as that used to measure histamine, histidine, carnosine and 3-methylhistamine. These findings suggest a role for carcinine in the carnosine-histidine-histamine metabolic pathway and the mammalian physiologic response to stress

Interactions of the histamine and hypocretin systems in CNS disorders.

Science.gov (United States)

Shan, Ling; Dauvilliers, Yves; Siegel, Jerome M

2015-07-01

Histamine and hypocretin neurons are localized to the hypothalamus, a brain area critical to autonomic function and sleep. Narcolepsy type 1, also known as narcolepsy with cataplexy, is a neurological disorder characterized by excessive daytime sleepiness, impaired night-time sleep, cataplexy, sleep paralysis and short latency to rapid eye movement (REM) sleep after sleep onset. In narcolepsy, 90% of hypocretin neurons are lost; in addition, two groups reported in 2014 that the number of histamine neurons is increased by 64% or more in human patients with narcolepsy, suggesting involvement of histamine in the aetiology of this disorder. Here, we review the role of the histamine and hypocretin systems in sleep-wake modulation. Furthermore, we summarize the neuropathological changes to these two systems in narcolepsy and discuss the possibility that narcolepsy-associated histamine abnormalities could mediate or result from the same processes that cause the hypocretin cell loss. We also review the changes in the hypocretin and histamine systems, and the associated sleep disruptions, in Parkinson disease, Alzheimer disease, Huntington disease and Tourette syndrome. Finally, we discuss novel therapeutic approaches for manipulation of the histamine system.

Involvement of the histamine H{sub 4} receptor in clozapine-induced hematopoietic toxicity: Vulnerability under granulocytic differentiation of HL-60 cells

Energy Technology Data Exchange (ETDEWEB)

Goto, Aya; Mouri, Akihiro; Nagai, Tomoko; Yoshimi, Akira; Ukigai, Mako; Tsubai, Tomomi; Hida, Hirotake [Division of Clinical Sciences and Neuropsychopharmacology, Faculty and Graduate School of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503 (Japan); Ozaki, Norio [Department of Psychiatry, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Noda, Yukihiro, E-mail: ynoda@meijo-u.ac.jp [Division of Clinical Sciences and Neuropsychopharmacology, Faculty and Graduate School of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503 (Japan)

2016-09-01

Clozapine is an effective antipsychotic for treatment-resistant schizophrenia, but can cause fatal hematopoietic toxicity as agranulocytosis. To elucidate the mechanism of hematopoietic toxicity induced by clozapine, we developed an in vitro assay system using HL-60 cells, and investigated the effect on hematopoiesis. HL-60 cells were differentiated by all-trans retinoic acid (ATRA) into three states according to the following hematopoietic process: undifferentiated HL-60 cells, those undergoing granulocytic ATRA-differentiation, and ATRA-differentiated granulocytic cells. Hematopoietic toxicity was evaluated by analyzing cell survival, cell proliferation, granulocytic differentiation, apoptosis, and necrosis. In undifferentiated HL-60 cells and ATRA-differentiated granulocytic cells, both clozapine (50 and 100 μM) and doxorubicin (0.2 µM) decreased the cell survival rate, but olanzapine (1–100 µM) did not. Under granulocytic differentiation for 5 days, clozapine, even at a concentration of 25 μM, decreased survival without affecting granulocytic differentiation, increased caspase activity, and caused apoptosis rather than necrosis. Histamine H{sub 4} receptor mRNA was expressed in HL-60 cells, whereas the expression decreased under granulocytic ATRA-differentiation little by little. Both thioperamide, a histamine H{sub 4} receptor antagonist, and DEVD-FMK, a caspase-3 inhibitor, exerted protection against clozapine-induced survival rate reduction, but not of live cell counts. 4-Methylhistamine, a histamine H{sub 4} receptor agonist, decreased the survival rate and live cell counts, as did clozapine. HL-60 cells under granulocytic differentiation are vulnerable under in vitro assay conditions to hematopoietic toxicity induced by clozapine. Histamine H{sub 4} receptor is involved in the development of clozapine-induced hematopoietic toxicity through apoptosis, and may be a potential target for preventing its occurrence through granulocytic differentiation

Measurement of plasma histamine: description of an improved method and normal values

International Nuclear Information System (INIS)

Dyer, J.; Warren, K.; Merlin, S.; Metcalfe, D.D.; Kaliner, M.

1982-01-01

The single isotopic-enzymatic assay of histamine was modified to increase its sensitivity and to facilitate measurement of plasma histamine levels. The modification involved extracting 3 H-1-methylhistamine (generated by the enzyme N-methyltransferase acting on histamine in the presence of S-[methyl- 3 H]-adenosyl-L-methionine) into chloroform and isolating the 3 H-1-methylhistamine by thin-layer chromatography (TLC). The TLC was developed in acetone:ammonium hydroxide (95:10), and the methylhistamine spot (Rf . 0.50) was identified with an o-phthalaldehyde spray, scraped from the plate, and assayed in a scintillation counter. The assay in plasma demonstrated a linear relationship from 200 to 5000 pg histamine/ml. Plasma always had higher readings than buffer, and dialysis of plasma returned these values to the same level as buffer, suggesting that the baseline elevations might be attributable to histamine. However, all histamine standard curves were run in dialyzed plasma to negate any additional influences plasma might exert on the assay. The arithmetic mean (+/- SEM) in normal plasma histamine was 318.4 +/- 25 pg/ml (n . 51), and the geometric mean was 280 +/- 35 pg/ml. Plasma histamine was significantly elevated by infusion of histamine at 0.05 to 1.0 micrograms/kg/min or by cold immersion of the hand of a cold-urticaria patient. Therefore this modified isotopic-enzymatic assay of histamine is extremely sensitive, capable of measuring fluctuations in plasma histamine levels within the normal range, and potentially useful in analysis of the role histamine plays in human physiology

Histamine is a modulator of metamorphic competence in Strongylocentrotus purpuratus (Echinodermata: Echinoidea

Directory of Open Access Journals (Sweden)

Sutherby Josh

2012-04-01

Full Text Available Abstract Background A metamorphic life-history is present in the majority of animal phyla. This developmental mode is particularly prominent among marine invertebrates with a bentho-planktonic life cycle, where a pelagic larval form transforms into a benthic adult. Metamorphic competence (the stage at which a larva is capable to undergo the metamorphic transformation and settlement is an important adaptation both ecologically and physiologically. The competence period maintains the larval state until suitable settlement sites are encountered, at which point the larvae settle in response to settlement cues. The mechanistic basis for metamorphosis (the morphogenetic transition from a larva to a juvenile including settlement, i.e. the molecular and cellular processes underlying metamorphosis in marine invertebrate species, is poorly understood. Histamine (HA, a neurotransmitter used for various physiological and developmental functions among animals, has a critical role in sea urchin fertilization and in the induction of metamorphosis. Here we test the premise that HA functions as a developmental modulator of metamorphic competence in the sea urchin Strongylocentrotus purpuratus. Results Our results provide strong evidence that HA leads to the acquisition of metamorphic competence in S. purpuratus larvae. Pharmacological analysis of several HA receptor antagonists and an inhibitor of HA synthesis indicates a function of HA in metamorphic competence as well as programmed cell death (PCD during arm retraction. Furthermore we identified an extensive network of histaminergic neurons in pre-metamorphic and metamorphically competent larvae. Analysis of this network throughout larval development indicates that the maturation of specific neuronal clusters correlates with the acquisition of metamorphic competence. Moreover, histamine receptor antagonist treatment leads to the induction of caspase mediated apoptosis in competent larvae. Conclusions We

Role of histamine receptors in the effects of histamine on the production of reactive oxygen species by whole blood phagocytes

Czech Academy of Sciences Publication Activity Database

Vašíček, Ondřej; Lojek, Antonín; Jančinová, V.; Nosál, R.; Číž, Milan

2014-01-01

Roč. 100, č. 1 (2014), s. 67-72 ISSN 0024-3205 R&D Projects: GA MŠk(CZ) LD11010 Institutional support: RVO:68081707 Keywords : Histamine * Histamine receptors * Reactive oxygen species Subject RIV: BO - Biophysics Impact factor: 2.702, year: 2014

Histamine poisoning and control measures in fish and fishery products

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Pierina eVisciano

2014-09-01

Full Text Available Histamine poisoning is one of the most common form of intoxication caused by the ingestion of fish and fishery products. Cooking, canning or freezing cannot reduce the levels of histamine because this compound is heat stable. All humans are susceptible to histamine and its effects can be described as intolerance or intoxication depending on the severity of the symptoms. The amount of histamine in food, the individual sensitivity and the detoxification activity in human organism represent the main factors affecting the toxicological response in consumers. Histamine is the only biogenic amine with regulatory limits set by European Legislation, up to a maximum of 200 mg/kg in fresh fish and 400 mg/kg in fishery products treated by enzyme maturation in brine.

Facilitating effect of histamine on spatial memory deficits induced by dizocilpine as evaluated by 8-arm radial maze in SD rats%组胺对地佐环平诱发的SD大鼠八臂迷宫空间记忆障碍的改善作用

Institute of Scientific and Technical Information of China (English)

黄育文; 陈忠; 胡薇薇; 张力三; 吴炜; 应力阳; 魏尔清

2003-01-01

AIM: To investigate whether or not histamine is involved in spatial memory deficits induced by dizocilpine (MK 801) as evaluated by 8-arm radial maze of rats. METHODS: 8-Arm (4-arm baited) radial maze was used to measure spatial memory in rats. RESULTS: Bilaterally intrahippocampal (ih) injection of MK-801 (0.3 μg/site) impaired working memory and reference memory in rats. Both histamine (50, 100 ng/site, ih) and intraperitoneal (ip) injection of histidine (100, 200 mg/kg) markedly improved the spatial memory deficits induced by MK-801. On the other hand, the ameliorating effect of histidine (100 mg/kg, ip) was completely antagonized by αfluoromethylhistidine (α-FMH, 5 μg/site, ih), a potent and selective histidine decarboxylase (HDC) inhibitor, and H1-antagonist pyrilamine (1 μg/site, ih), but not by H2-antagonist cimetidine, even at a high dose (2.5 μg/site, ih).CONCLUSION: The hippocampal histamine plays an important role in the ameliorating effect on MK-801-induced spatial memory deficits, and its action is mediated through postsynaptic H1-receptor.

Study to investigate the difference in reaction to intracutaneously and orally administered histamine between suspected histamine-intolerant patients and healthy volunteers

NARCIS (Netherlands)

den Broeder E; Kortboyer JM; Koers WJ; Bruijnzeel-Koomen CAFM; de Haan-Brand A; Wolthers BG; Breukelman H; Meulenbelt J; NVIC; ARO; afdeling Dermatologie en Allergologie (Academisch Ziekenhuis Utrecht); afdeling KCSB (Academisch Ziekenhuis Groningen)

1996-01-01

In een dubbelblinde placebo gecontroleerde, vergelijkende studie werd aan 16 histamine intolerante patienten en aan 16 gezonde proefpersonen histamine toegediend. Het doel van de studie was het ontwikkelen van een relatief simpele en betrouwbare test voor het stellen van de diagnose

Evaluation of the Histamine Content and Potential Toxicity of Some of Consumable food

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M Zarei

2017-02-01

Full Text Available ABSTRACT Background & aim: Consuming high amounts of histamine with food causes histamine poisoning among its consumers. Much information about the content of histamine in various food products is not available in the country. In the present study, the amount of histamine in food samples consumed in human diet which are based on existing data sources can contain histamine were measured. Methods: In the present study, 240 samples of 16 different types of food consumed in the human diet were examined. Histamine was extracted with 75 % ethanol- 0.4 N HCl in fresh and canned fish samples and extracted in other samples with  0.1 N HCl. After passing the extracts through ion exchange chromatography, the fluorescence derivative of histamine which was generated by O-phthaldialdehyde and the amount of fluorescent light was measured at excitation wavelength of 350 nm and emission wavelength of 444 nm respectively. Data were analyzed using descriptive statistics. Results: Spinach, fresh fish, canned fish and aubergine samples showed the high level of histamine with the mean levels of 5.04, 3.83, 2.77 and 2.64 mg/100g respectively. All samples tested contains histamine but 53.3, 20.0, 13.3 and 13.3 percent of the samples of these foods contains higher amounts histamine (5mg/100gr  respectively.Low levels of histamine was observed in a number of samples including tomato, pickles, nuts, bananas, oranges, melons, cheese, curd, yogurt and dough but no detectable histamine was found  olive and tea. Conclusion: In addition to confirming the fact that fish and seafood products have a high risk of histamine poisoning, but it showed that the risk of histamine poisoning in humans after consumption of fish and its products will not be less than spinach and aubergine.

PENINGKATAN KADAR HISTAMIN PADA IKAN LAUT YANG SUDAH DIOLAH

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Djarismawati Djarismawati

2012-10-01

Full Text Available  It was very difficult to recover the condition of people·s nutntion especially among the children during the economic crisis, even though that problem could be overcome by consuming protein especially from sea-fish. But handling food originated from sea-fish was very difficult, because sea-fish could be easily contaminated by toxins. In this study the histamine contents in fresh and processed sea-fish will be analized. The objective of the study was to test the best way of fish cooking to minimize the histamine content. The limiting time of the fish remain fresh after taken from the market was also studied. The result showed that the time taken to bring the fish from the sampling points to the laboratory and the way of fish cooking would influence the histamine content in cooked fish. We also found that cooking fish with coconut milk has resulted the lowest histamine content as compared with frying or roasting. Keywords: histamine, sea fish, nutrition

DETERMINATION OF HISTAMINE IN FISH USING ELISA TECHNIQUE

NARCIS (Netherlands)

KRUGER, C; SEWING, U; STENGEL, G; KEMA, [No Value; WESTERMANN, J; MANZ, B

1995-01-01

The analysis of histamine in fish and fish products via competitive ELISA is described. The advantages of this method are easy sample preparation and handling, screening capabilities, and low costs. Automation enables the performance of the assay with higher series of samples. The Histamine-ELISA is

Determination of histamine in Iranian cheese using enzyme-linked ...

African Journals Online (AJOL)

john

enzyme-linked immunosorbent assay (ELISA) method. Mojtaba ... Histamine is a simple chemical substance created during processing of the amine acid histidine. Histamine is also an .... Institute of environment Health and Forensic. Sciences ...

Heteroreceptor Complexes Formed by Dopamine D1, Histamine H3, and N-Methyl-D-Aspartate Glutamate Receptors as Targets to Prevent Neuronal Death in Alzheimer's Disease.

Science.gov (United States)

Rodríguez-Ruiz, Mar; Moreno, Estefanía; Moreno-Delgado, David; Navarro, Gemma; Mallol, Josefa; Cortés, Antonio; Lluís, Carme; Canela, Enric I; Casadó, Vicent; McCormick, Peter J; Franco, Rafael

2017-08-01

Alzheimer's disease (AD) is a neurodegenerative disorder causing progressive memory loss and cognitive dysfunction. Anti-AD strategies targeting cell receptors consider them as isolated units. However, many cell surface receptors cooperate and physically contact each other forming complexes having different biochemical properties than individual receptors. We here report the discovery of dopamine D 1 , histamine H 3 , and N-methyl-D-aspartate (NMDA) glutamate receptor heteromers in heterologous systems and in rodent brain cortex. Heteromers were detected by co-immunoprecipitation and in situ proximity ligation assays (PLA) in the rat cortex where H 3 receptor agonists, via negative cross-talk, and H 3 receptor antagonists, via cross-antagonism, decreased D 1 receptor agonist signaling determined by ERK1/2 or Akt phosphorylation, and counteracted D 1 receptor-mediated excitotoxic cell death. Both D 1 and H 3 receptor antagonists also counteracted NMDA toxicity suggesting a complex interaction between NMDA receptors and D 1 -H 3 receptor heteromer function. Likely due to heteromerization, H 3 receptors act as allosteric regulator for D 1 and NMDA receptors. By bioluminescence resonance energy transfer (BRET), we demonstrated that D 1 or H 3 receptors form heteromers with NR1A/NR2B NMDA receptor subunits. D 1 -H 3 -NMDA receptor complexes were confirmed by BRET combined with fluorescence complementation. The endogenous expression of complexes in mouse cortex was determined by PLA and similar expression was observed in wild-type and APP/PS1 mice. Consistent with allosteric receptor-receptor interactions within the complex, H 3 receptor antagonists reduced NMDA or D 1 receptor-mediated excitotoxic cell death in cortical organotypic cultures. Moreover, H 3 receptor antagonists reverted the toxicity induced by ß 1-42 -amyloid peptide. Thus, histamine H 3 receptors in D 1 -H 3 -NMDA heteroreceptor complexes arise as promising targets to prevent neurodegeneration.

Cold urticaria: inhibition of cold-induced histamine release by doxantrazole.

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Bentley-Phillips, C B; Eady, R A; Greaves, M W

1978-10-01

Thirteen patients with cold urticaria were studied to assess the effect of the systemic drug doxantrazole, which has actions resembling disodium cromoglycate, on cold evoked histamine release. The patients, all of whom developed an immediate local whealing response after cooling of the forearm, demonstrated release of histamine into venous blood draining that forearm. Following doxantrazole treatment, significant suppression of histamine release occurred. In some but not all patients this was accompanied by diminution of urtication in response to cooling. A double-blind study was carried out in 3 subjects, all of whom showed diminished cold-stimulated histamine release after doxantrazole. Two of these showed clinical improvement. Doxantrazole had no effect on erythema due to intradermal histamine, but did suppress the erythematous reaction to intradermal injection of compound 48/80. Our results suggest that doxantrazole or related anti-allergic agents might be useful in the treatment of cold urticaria.

Histamine H3 Receptors Decrease Dopamine Release in the Ventral Striatum by Reducing the Activity of Striatal Cholinergic Interneurons.

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Varaschin, Rafael Koerich; Osterstock, Guillaume; Ducrot, Charles; Leino, Sakari; Bourque, Marie-Josée; Prado, Marco A M; Prado, Vania Ferreira; Salminen, Outi; Rannanpää Née Nuutinen, Saara; Trudeau, Louis-Eric

2018-04-15

Histamine H 3 receptors are widely distributed G i -coupled receptors whose activation reduces neuronal activity and inhibits release of numerous neurotransmitters. Although these receptors are abundantly expressed in the striatum, their modulatory role on activity-dependent dopamine release is not well understood. Here, we observed that histamine H 3 receptor activation indirectly diminishes dopamine overflow in the ventral striatum by reducing cholinergic interneuron activity. Acute brain slices from C57BL/6 or channelrhodopsin-2-transfected DAT-cre mice were obtained, and dopamine transients evoked either electrically or optogenetically were measured by fast-scan cyclic voltammetry. The H 3 agonist α-methylhistamine significantly reduced electrically- evoked dopamine overflow, an effect blocked by the nicotinic acetylcholine receptor antagonist dihydro-β-erythroidine, suggesting involvement of cholinergic interneurons. None of the drug treatments targeting H 3 receptors affected optogenetically evoked dopamine overflow, indicating that direct H 3 -modulation of dopaminergic axons is unlikely. Next, we used qPCR and confirmed the expression of histamine H 3 receptor mRNA in cholinergic interneurons, both in ventral and dorsal striatum. Activation of H 3 receptors by α-methylhistamine reduced spontaneous firing of cholinergic interneurons in the ventral, but not in the dorsal striatum. Resting membrane potential and number of spontaneous action potentials in ventral-striatal cholinergic interneurons were significantly reduced by α-methylhistamine. Acetylcholine release from isolated striatal synaptosomes, however, was not altered by α-methylhistamine. Together, these results indicate that histamine H 3 receptors are important modulators of dopamine release, specifically in the ventral striatum, and that they do so by decreasing the firing rate of cholinergic neurons and, consequently, reducing cholinergic tone on dopaminergic axons. Copyright © 2018 IBRO

Effect of FRG-8813, a new-type histamine H(2)-receptor antagonist, on the recurrence of gastric ulcer after healing by drug treatment in rats.

Science.gov (United States)

Ajioka, H; Miyake, H; Matsuura, N

2000-08-01

We investigated the recurrence of ulcers in rats after treatment with FRG-8813, (+/-)-2-(furfurylsulfinyl)-N-[4- [4-(piperidinomethyl)-2-pyridyl] oxy-(Z)-2-butenyl] acetamide, a novel histamine H(2)-receptor antagonist. Chronic gastric ulcers were induced by serosa-searing with a hot metal bar, and the ulcer healing and recurrence after treatment with FRG-8813 or famotidine were evaluated by endoscopy for 160 days. At the dose of 30 mg/kg p. o., once daily, the treatment with FRG-8813 or famotidine for 60 days, which was stopped earlier if the ulcer had healed, accelerated the ulcer healing significantly. A subsequent follow-up study on the healed rats showed that the cumulative recurrence rate of rats healed by FRG-8813 was lower than that of naturally healed rats or rats healed by famotidine. In many cases of rats healed by FRG-8813, the regenerated mucosa was normal in contrast with the control of famotidine-healed animals. The mucosal regeneration index of the gastric ulcer after 10 days' administration of FRG-8813 was significantly higher than that obtained with famotidine. After cessation of the treatment with famotidine for 7 days, rebound hyperacidity was induced; but such rebound did not occur with FRG-8813. Considering the low recurrence rate of ulcers after FRG-8813 treatment, we suggest that FRG-8813 treatment may provide additional benefits in peptic ulcer therapy. Copyright 2000 S. Karger AG, Basel

Determination of histamine in milkfish stick implicated in food-borne poisoning

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Yi-Chen Lee

2016-01-01

Full Text Available An incident of food-borne poisoning causing illness in 37 victims due to ingestion of fried fish sticks occurred in September 2014, in Tainan city, southern Taiwan. Leftovers of the victims' fried fish sticks and 16 other raw fish stick samples from retail stores were collected and tested to determine the occurrence of histamine and histamine-forming bacteria. Two suspected fried fish samples contained 86.6 mg/100 g and 235.0 mg/100 g histamine; levels that are greater than the potential hazard action level (50 mg/100 g in most illness cases. Given the allergy-like symptoms of the victims and the high histamine content in the suspected fried fish samples, this food-borne poisoning was strongly suspected to be caused by histamine intoxication. Moreover, the fish species of suspected samples was identified as milkfish (Chanos chanos, using polymerase chain reaction direct sequence analysis. In addition, four of the 16 commercial raw milkfish stick samples (25% had histamine levels greater than the US Food & Drug Administration guideline of 5.0 mg/100 g for scombroid fish and/or products. Ten histamine-producing bacterial strains, capable of producing 373–1261 ppm of histamine in trypticase soy broth supplemented with 1.0% L-histidine, were identified as Enterobacter aerogenes (4 strains, Enterobacter cloacae (1 strain, Morganella morganii (2 strains, Serratia marcescens (1 strain, Hafnia alvei (1 strain, and Raoultella orithinolytica (1 strain, by 16S ribosomal DNA sequencing with polymerase chain reaction amplification.

Anti-histaminic potentials of Cnidoscolus aconitifolius in the ...

African Journals Online (AJOL)

Similarly, the observable significant reduction in the paw size was comparable to the Ibuprofen (100 mg/kg). Different concentrations of EECA (0.025, 0.05, 0.1 and 0.2 mg/kg) were assessed on the histamine release from the mast cells. The rats administered with 0.2mg/kg had the most profound effects on the histamine ...

Identification of amino acids involved in histamine potentiation of GABA(A receptors

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Ulrike eThiel

2015-05-01

Full Text Available Histamine is a neurotransmitter involved in a number of physiological and neuronal functions. In mammals, such as humans and rodents, the histaminergic neurons found in the tuberomamillary nucleus (TMN project widely throughout the central nervous system (CNS. Histamine acts as positive modulator of GABA(A receptors (GABA(ARs and, in high concentrations (10 mM, as negative modulator of the strychnine-sensitive glycine receptor. However, the exact molecular mechanisms by which histamine acts on GABA(ARs are unknown. In our study, we aimed to identify amino acids potentially involved in the modulatory effect of histamine on GABA(ARs. We expressed GABA(ARs with 12 different point mutations in Xenopus laevis oocytes and characterized the effect of histamine on GABA-induced currents using the two-electrode voltage clamp technique. Our data demonstrate that the amino acid residues ß2(N265 and ß2(M286, which are important for modulation by propofol, are not involved in the action of histamine. However, we found that histamine modulation is dependent on the amino acid residues alpha1(R120, ß2(Y157, ß3(D163, ß3(V175 and ß3(Q185. We showed that the amino acid residues ß2(Y157 and ß3(Q185 mediate the positive modulatory effect of histamine on GABA-induced currents, whereas alpha1(R120 and ß2(D163 form a potential histamine interaction site in GABA(ARs.

Spatial changes in acid secretion from isolated stomach tissue using a pH-histamine sensing microarray.

Science.gov (United States)

Bitziou, Eleni; O'Hare, Danny; Patel, Bhavik Anil

2010-03-01

The acid secretion mechanism can be studied by measuring a series of metabolic markers and neurotransmitters from in vitro isolated tissue. A microelectrode array was used to monitor proton concentration and histamine levels from isolated guinea pig stomach tissue. The device was partially modified using iridium oxide to form a series of pH sensors, whereas unmodified gold microelectrodes were used to measure the level of histamine in the gut. Real-time measurements in the presence of the H2-receptor antagonist ranitidine produced significant decreases in the overall Delta pH response, as expected. Also, a significant variation in the Delta pH response in between pH sensors was observed in the presence of pharmacological treatment due to structural features of the tissue. No significant differences in Delta i(H) were detected in the presence of ranitidine as expected. More significantly, clear variations in Delta pH responses between animals in control conditions and those in the presence of ranitidine was observed highlighting possible variation in parietal cell density and/or variations in tissue activity. These results identify great possibilities in applying these multi-sensing devices as a long-term stable personalised diagnostic tool for pharmacological screening and disease status.

Histamine protects bone marrow against cellular damage induced by Ionizing radiation

International Nuclear Information System (INIS)

Medina, Vanina; Sambuco, Lorena; Massari, Noelia; Cricco, Graciela; Martin, Gabriela; Bergoc, Rosa; Rivera, Elena S.

2008-01-01

After surgery, radiotherapy is arguably one of the most important treatments for cancer, especially for localized disease that has not spread. However, ionizing radiation is toxic not only to tumor cells but also to healthy tissues causing serious adverse effects to patients. We have recently reported that histamine prevents ionizing radiation-induced toxicity on mouse small intestine. The aim of the present work was to determine whether histamine is able to protect bone marrow cells against ionizing radiation damage. For that purpose 56 mice were divided into 4 groups. Histamine and Histamine-10Gy groups received a daily subcutaneous histamine injection (0.1 mg/kg) starting 20 hours before irradiation and continued till the end of experimental period; untreated group received saline. Histamine-10Gy and untreated-10Gy groups were irradiated with a single dose on whole-body using Cesium-137 source (7 Gy/min) and were sacrificed 3 days after irradiation. Bone marrow was removed, fixed and stained with hematoxylin and eosin. The number of megacariocytes per 40x field, bone marrow tropism, edema, vascular damage, and other histological characteristics of bone marrow cells were evaluated. We further determined by immunohistochemistry the expression of proliferating cell nuclear antigen (PCNA) and cells in the S phase of the cell cycle were identified by immunohistochemical detection of 5-bromo-2'-deoxyuridine (BrdU) incorporation. Results indicate that histamine treatment substantially reduced the grade of aplasia, the edema and the vascular damage induced by ionizing radiation on bone marrow. Additionally, histamine preserved medullar components increasing significantly the number of megacariocytes per field (5.4 ± 0.4 vs. 2.8 ± 0.4 in Control-10 Gy, P<0.01). This effect was associated with an increased proliferation rate determined by the augmented PCNA expression and BrdU incorporation of bone marrow cells. On the basis of these results, we conclude that histamine

PENGGUNAAN EKSTRAK TEH HIJAU (Camellia sinensis SEBAGAI PENGHAMBAT PEMBENTUKAN HISTAMIN PADA IKAN SEBELUM DIOLAH

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Endang Sri Heruwati

2009-12-01

Full Text Available Penelitian penggunaan ekstrak teh hijau (Camellia sinensis sebagai penghambat pembentukan histamin pada ikan telah dilakukan. Ikan, terutama dari jenis skombroid, sangat rentan mengalami kerusakan karena terjadinya perubahan asam amino histidin yang terkandung dalam ikan menjadi senyawa histamin yang bersifat alergen, yang dikatalisasi oleh enzim histamin dekarboksilase (HDC. Teh hijau diketahui mengandung polifenol berupa senyawa epigalokatekingalat (EGCG yang merupakan penghambat enzim HDC, sehingga dekarboksilasi histidin menjadi histamin dapat dicegah. Perendaman ikan tongkol dalarn ekstrak teh hijau pada konsentrasi 0, 2, dan 4% dilakukan selama 30 menit, diikuti dengan pernindangan dalam larutan gararn 15% selama 30 menit diteruskan dengan penyimpanan ikan pindang pada suhu kamar. Pengambilan sampel dilakukan setiap hari selarna 4 hari penyimpanan untuk diamati perubahan mutu kimiawi (TVB dan kadar histarnin, mikrobiologi JPC dan bakteri pembentuk histamin, serta organoleptik (kenampakan, bau, tekstur, lendir, rasa. Hasil penelitian menunjukkan bahwa ikan yang direndam dalam ekstrak teh 4% mempunyai kadar histamin 21,3 ppm, jauh lebih rendah dibandingkan dengan ikan yang direndam dalam ekstrak teh 2% dan 0% yang masing-masing mencapai 64,4 pprn dan 101,4 ppm. Penghambatan pembentukan histamin oleh ekstrak teh hijau masih terjadi selama penyimpanan, yang terlihat dari rendahnya jumlah bakteri pembentuk histarnin dan kadar histamin dibandingkan dengan kontrol. Pada penyimpanan hari ke-3, penghambatan pembentukan histamin oleh ekstrak teh hijau tidak efektif, kemungkinan karena terlalu tingginya jurnlah bakteri pembentuk histamin, yaitu mencapai 108 cfu/g.

High-performance liquid chromatographic determination of histamine in biological samples: the cerebrospinal fluid challenge--a review.

Science.gov (United States)

Wang, Zhaopin; Wu, Juanli; Wu, Shihua; Bao, Aimin

2013-04-24

Histamine, a neurotransmitter crucially involved in a number of basic physiological functions, undergoes changes in neuropsychiatric disorders. Detection of histamine in biological samples such as cerebrospinal fluid (CSF) is thus of clinical importance. The most commonly used method for measuring histamine levels is high performance liquid chromatography (HPLC). However, factors such as very low levels of histamine, the even lower CSF-histamine and CSF-histamine metabolite levels, especially in certain neuropsychiatric diseases, rapid formation of histamine metabolites, and other confounding elements during sample collection, make analysis of CSF-histamine and CSF-histamine metabolites a challenging task. Nonetheless, this challenge can be met, not only with respect to HPLC separation column, derivative reagent, and detector, but also in terms of optimizing the CSF sample collection. This review aims to provide a general insight into the quantitative analyses of histamine in biological samples, with an emphasis on HPLC instruments, methods, and hyphenated techniques, with the aim of promoting the development of an optimal and practical protocol for the determination of CSF-histamine and/or CSF-histamine metabolites. Copyright © 2013 Elsevier B.V. All rights reserved.

Cost-Effectiveness of Histamine2 Receptor Antagonists Versus Proton Pump Inhibitors for Stress Ulcer Prophylaxis in Critically Ill Patients.

Science.gov (United States)

Hammond, Drayton A; Kathe, Niranjan; Shah, Anuj; Martin, Bradley C

2017-01-01

To determine the cost-effectiveness of stress ulcer prophylaxis with histamine 2 receptor antagonists (H2RAs) versus proton pump inhibitors (PPIs) in critically ill and mechanically ventilated adults. A decision analytic model estimating the costs and effectiveness of stress ulcer prophylaxis (with H2RAs and PPIs) from a health care institutional perspective. Adult mixed intensive care unit (ICU) population who received an H2RA or PPI for up to 9 days. Effectiveness measures were mortality during the ICU stay and complication rate. Costs (2015 U.S. dollars) were combined to include medication regimens and untoward events associated with stress ulcer prophylaxis (pneumonia, Clostridium difficile infection, and stress-related mucosal bleeding). Costs and probabilities for complications and mortality from complications came from randomized controlled trials and observational studies. A base case scenario was developed with pooled data from an observational study and meta-analysis of randomized controlled trials. Scenarios based on observational and meta-analysis data alone were evaluated. Outcomes were expected and incremental costs, mortalities, and complication rates. Univariate sensitivity analyses were conducted to determine the influence of inputs on cost, mortality, and complication rates. Monte Carlo simulations evaluated second-order uncertainty. In the base case scenario, the costs, complication rates, and mortality rates were $9039, 17.6%, and 2.50%, respectively, for H2RAs and $11,249, 22.0%, and 3.34%, respectively, for PPIs, indicating that H2RAs dominated PPIs. The observational study-based model provided similar results; however, in the meta-analysis-based model, H2RAs had a cost of $8364 and mortality rate of 3.2% compared with $7676 and 2.0%, respectively, for PPIs. At a willingness-to-pay threshold of $100,000/death averted, H2RA therapy was superior or preferred 70.3% in the base case and 97.0% in the observational study-based scenario. PPI therapy

HISTAMINE H3 RECEPTOR INVERSE AGONISTS ON COGNITIVE AND MOTOR PROCESSES: RELEVANCE TO ALZHEIMER’S DISEASE, ADHD, SCHIZOPHRENIA AND DRUG ABUSE

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Divya eVohora

2012-10-01

Full Text Available Histamine H3 receptor antagonists/ inverse agonists possess potential to treat diverse disease states of the central nervous system (CNS. Cognitive dysfunction and motor impairments are the hallmark of multifarious neurodegenerative and/or psychiatric disorders. This review presents the various neurobiological/ neurochemical evidences available so far following H3 receptor inverse agonists/ antagonists in the pathophysiology of Alzheimer’s disease (AD, attention-deficit hyperactivity disorder (ADHD, schizophrenia and drug abuse each of which is accompanied by deficits of some aspects of cognitive and/or motor functions. Whether the H3 receptor inverse agonism modulates the neurochemical basis underlying the disease condition or affects only the cognitive/motor component of the disease process is discussed with the aim to provide a rationale for their use in diverse disease states that are interlinked and are accompanied by some common motor, cognitive and attentional deficits.

FT-Raman and QM/MM study of the interaction between histamine and DNA

International Nuclear Information System (INIS)

Ruiz-Chica, A.J.; Soriano, A.; Tunon, I.; Sanchez-Jimenez, F.M.; Silla, E.; Ramirez, F.J.

2006-01-01

The interaction between histamine and highly polymerized calf-thymus DNA has been investigated using FT-Raman spectroscopy and the hybrid QM/MM (quantum mechanics/molecular mechanics) methodology. Raman spectra of solutions containing histamine and calf-thymus DNA, at different molar ratios, were recorded. Solutions were prepared at physiological settings of pH and ionic strength, using both natural and heavy water as the solvent. The analysis of the spectral changes on the DNA Raman spectra when adding different concentrations of histamine allowed us to identify the reactive sites of DNA and histamine, which were used to built two minor groove and one intercalated binding models. They were further used as starting points of the QM/MM theoretical study. However, minimal energy points were only reached for the two minor groove models. For each optimized structure, we calculated analytical force constants of histamine molecule in order to perform the vibrational dynamics. Normal mode descriptions allowed us to compare calculated wavenumbers for DNA-interacting histamine to those measured in the Raman spectra of DNA-histamine solutions

Effects of the H(2)-receptor antagonist ranitidine on gastric motor function after a liquid meal in healthy humans

DEFF Research Database (Denmark)

Madsen, Jan Lysgård; Graff, J

2008-01-01

Objective. Studies on animals have shown that histamine may be involved in the regulation of gastrointestinal smooth muscle tone. However, the role of histamine in the regulation of human gastric motor function is not clear. This study examined the effect of ranitidine, an H(2)-receptor antagonist......, on gastric volume and gastric emptying after a liquid meal in healthy humans. Material and methods. Twelve healthy volunteers participated in a randomized crossover study with 50 mg ranitidine as a bolus intravenously versus no medication. Gastric volume at baseline was determined with single photon emission...... computed tomography (SPECT) after intravenous injection of 99(m)Tc-pertechnetate. After ingestion of a 600-mL liquid meal radiolabelled with (111)In-diethylenetriaminepentaacetic acid, dual-isotope technique with SPECT and planar imaging assessed gastric volume as well as gastric emptying. Results...

Effects of the H2-receptor antagonist ranitidine on gastric motor function after a liquid meal in healthy humans

DEFF Research Database (Denmark)

Madsen, J.L.; Graff, J.

2008-01-01

OBJECTIVE: Studies on animals have shown that histamine may be involved in the regulation of gastrointestinal smooth muscle tone. However, the role of histamine in the regulation of human gastric motor function is not clear. This study examined the effect of ranitidine, an H(2)-receptor antagonist......, on gastric volume and gastric emptying after a liquid meal in healthy humans. MATERIAL AND METHODS: Twelve healthy volunteers participated in a randomized crossover study with 50 mg ranitidine as a bolus intravenously versus no medication. Gastric volume at baseline was determined with single photon emission...... computed tomography (SPECT) after intravenous injection of 99(m)Tc-pertechnetate. After ingestion of a 600-mL liquid meal radiolabelled with (111)In-diethylenetriaminepentaacetic acid, dual-isotope technique with SPECT and planar imaging assessed gastric volume as well as gastric emptying. RESULTS...

Histamine as an emergent indoor contaminant: Accumulation and persistence in bed bug infested homes.

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Zachary C DeVries

Full Text Available Histamine is used in bronchial and dermal provocation, but it is rarely considered an environmental risk factor in allergic disease. Because bed bugs defecate large amounts of histamine as a component of their aggregation pheromone, we sought to determine if histamine accumulates in household dust in bed bug infested homes, and the effects of bed bug eradication with spatial heat on histamine levels in dust. We collected dust in homes and analyzed for histamine before, and up to three months after bed bug eradication. Histamine levels in bed bug infested homes were remarkably high (mean = 54.6±18.9 μg/100 mg of sieved household dust and significantly higher than in control homes not infested with bed bugs (mean < 2.5±1.9 μg/100 mg of sieved household dust. Heat treatments that eradicated the bed bug infestations failed to reduce histamine levels, even three months after treatment. We report a clear association between histamine levels in household dust and bed bug infestations. The high concentrations, persistence, and proximity to humans during sleep suggest that bed bug-produced histamine may represent an emergent contaminant and pose a serious health risk in the indoor environment.

Histamine and the regulation of body weight

DEFF Research Database (Denmark)

Jørgensen, Emilie A; Knigge, Ulrich; Warberg, Jørgen

2007-01-01

Energy intake and expenditure is regulated by a complex interplay between peripheral and central factors. An exhaustive list of peptides and neurotransmitters taking part in this complex regulation of body weight exists. Among these is histamine, which acts as a central neurotransmitter. In the p......Energy intake and expenditure is regulated by a complex interplay between peripheral and central factors. An exhaustive list of peptides and neurotransmitters taking part in this complex regulation of body weight exists. Among these is histamine, which acts as a central neurotransmitter...

Intra-cerebellar microinjection of histamine enhances memory consolidation of inhibitory avoidance learning in mice via H2 receptors.

Science.gov (United States)

Gianlorenço, A C L; Canto-de-Souza, A; Mattioli, R

2013-12-17

Studies have demonstrated the relationship between the histaminergic system and the cerebellum, and we intend to investigate the role of the cerebellar histaminergic system on memory consolidation. This study investigated the effect of intra-cerebellar microinjection of histamine on memory retention of inhibitory avoidance in mice, and the role of H1 and H2 receptors in it. The cerebellar vermis of male mice were implanted with guide cannulae, and after three days of recovery, the inhibitory avoidance test was performed. Immediately after a training session, animals received a microinjection of histaminergic drugs: in the experiment 1, saline (SAL) or histamine (HA 0.54, 1.36, 2.72 or 4.07 nmol); experiment 2, SAL or 1.36 nmol HA 5 min after a pretreatment with 0.16 nmol chlorpheniramine (CPA) or SAL; and experiment 3, SAL or 1.36 nmol HA 5 min after a pretreatment with 2.85 nmol ranitidine (RA) or SAL. Twenty-four hours later, a retention test was performed. The data were analyzed using one-way analysis of variance (ANOVA) and Duncan's tests. In experiment 1, animals microinjected with 1.36 nmol HA showed a higher latency to cross to the dark compartment compared to controls and to 2.72 and 4.07 nmol HA groups. In experiment 2, the combined infusions revealed difference between control (SAL+SAL) and SAL+HA and CPA+HA; while in the experiment 3 the analysis indicated differences in retention latency between mice injected with SAL+SAL and SAL+HA. The groups that received the H2 antagonist RA did not show difference compared to control. These results indicate that 1.36 nmol HA enhances memory consolidation of inhibitory avoidance learning in mice and that the pretreatment with H2 antagonist RA was able to prevent this effect. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

[Effect of nociceptin on histamine and serotonin release in the central nervous system].

Science.gov (United States)

Gyenge, Melinda; Hantos, Mónika; Laufer, Rudolf; Tekes, Korniléa

2006-01-01

Role in pain sensation of both nociceptin (NC), the bioactive heptadecapeptide sequence of preproorphaninFQ and of histamine has been widely evidenced in the central nervous system (CNS). In the current series of experiments effect of intracerebroventricularly (i.c.v.) administered NC (5.5 nmol/rat) on histamine and serotonin levels in blood plasma, CSF and brain areas (hypothalamus and hippocampus) was studies and compared to the effect of the mast cell degranulator Compound 48/80(100microg/kg, i.c.v.) and the neuroactive peptide Substance P (50nmol/rat, i.c.v.). It was found that all the three compounds increased the histamine level in the CNS, however their activity concerning the mast cell-, and neuronal histamine release is different. NC could release histamine from both the mast cells and the neurons and it decreased CNS serotonin levels. Substance P was found the most potent in increasing CNS histamine levels. Compound 48/80 treatment resulted in elevated histamine levels both in the CNS and blood plasma. It is concluded that the histamine releasing effects of i.c.v. administered NC and SP are limited to the CNS, but in the effect of Compound 48/80 its blood-brain barrier impairing activity is also involved. Data also demonstrate that NC has significant effect on both the histaminergic and serotonergic neurotransmission in the CNS.

Immunochemical cross-reactivity between albumin and solid-phase adsorbed histamine

DEFF Research Database (Denmark)

Poulsen, L K; Nolte, H; Søndergaard, I

1990-01-01

For production of an antibody against histamine, this was coupled to human serum albumin (HSA) and used for immunization of rabbits. To test the antiserum, an immunoradiometric assay was developed comprising solid-phase bound histamine, antisera and radiolabelled protein A. Titration and inhibition...

Non-Imidazole Histamine H₃ Ligands. Part VII. Synthesis, In Vitro and In Vivo Characterization of 5-Substituted-2-thiazol-4-n-propylpiperazines.

Science.gov (United States)

Guryn, Roman; Staszewski, Marek; Stasiak, Anna; McNaught Flores, Daniel; Fogel, Wiesława Agnieszka; Leurs, Rob; Walczyński, Krzysztof

2018-02-03

H₃ receptors present on histaminergic and non-histaminergic neurons, act as autoreceptors or heteroreceptors controlling neurotransmitter release and synthesis. Previous, studies have found that the compound N -methyl- N -3-phenylalkyl-2-[2-(4-n-propylpiperazin-1-yl)-1,3-thiazol-5-yl]ethan-1-amine ( ADS-531, 2c ) exhibits high in vitro potency toward H₃ guinea pig jejunal receptors, with pA₂ = 8.27. To optimize the structure of the lead compound ADS-531 , a series of 5-substituted-2-thiazol-4- n -propylpiperazines 3 were synthesized and subjected to in vitro pharmacological characterization; the alkyl chain between position 2 of the thiazole ring and the terminal secondary N -methylamino function was elongated from three to four methylene groups and the N -methylamino functionality was substituted by benzyl-, 2-phenylethyl-, and 3-phenyl-propyl- moieties. SAR studies on novel non-imidazole, 5-substituted-2-thiazol-4- n -propyl-piperazines 3 showed that the most active compound 3a (pA₂ = 8.38), additionally possessed a weak competitive H₁-antagonistic activity. Therefore, compound ADS-531 , which did not exhibit any H₁-antagonistic activity, was chosen for further evaluation for its affinity to the recombinant rat and human histamine H₃ receptors (rH₃R and hH₃R, respectively). ADS-531 exhibited nanomolar affinity for both rH₃R and hH₃R receptors. It was also shown that, ADS-531 given subchronically to rats (s.c. 3 mg/kg, 5 days) penetrated the brain, where it affected dopamine, noradrenaline and serotonin concentration; however, it did not affect histamine concentration nor feeding behavior.

TASK Channels on Basal Forebrain Cholinergic Neurons Modulate Electrocortical Signatures of Arousal by Histamine.

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Vu, Michael T; Du, Guizhi; Bayliss, Douglas A; Horner, Richard L

2015-10-07

Basal forebrain cholinergic neurons are the main source of cortical acetylcholine, and their activation by histamine elicits cortical arousal. TWIK-like acid-sensitive K(+) (TASK) channels modulate neuronal excitability and are expressed on basal forebrain cholinergic neurons, but the role of TASK channels in the histamine-basal forebrain cholinergic arousal circuit is unknown. We first expressed TASK channel subunits and histamine Type 1 receptors in HEK cells. Application of histamine in vitro inhibited the acid-sensitive K(+) current, indicating a functionally coupled signaling mechanism. We then studied the role of TASK channels in modulating electrocortical activity in vivo using freely behaving wild-type (n = 12) and ChAT-Cre:TASK(f/f) mice (n = 12), the latter lacking TASK-1/3 channels on cholinergic neurons. TASK channel deletion on cholinergic neurons significantly altered endogenous electroencephalogram oscillations in multiple frequency bands. We then identified the effect of TASK channel deletion during microperfusion of histamine into the basal forebrain. In non-rapid eye movement sleep, TASK channel deletion on cholinergic neurons significantly attenuated the histamine-induced increase in 30-50 Hz activity, consistent with TASK channels contributing to histamine action on basal forebrain cholinergic neurons. In contrast, during active wakefulness, histamine significantly increased 30-50 Hz activity in ChAT-Cre:TASK(f/f) mice but not wild-type mice, showing that the histamine response depended upon the prevailing cortical arousal state. In summary, we identify TASK channel modulation in response to histamine receptor activation in vitro, as well as a role of TASK channels on cholinergic neurons in modulating endogenous oscillations in the electroencephalogram and the electrocortical response to histamine at the basal forebrain in vivo. Attentive states and cognitive function are associated with the generation of γ EEG activity. Basal forebrain

Histamine as an emergent indoor contaminant: Accumulation and persistence in bed bug infested homes.

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DeVries, Zachary C; Santangelo, Richard G; Barbarin, Alexis M; Schal, Coby

2018-01-01

Histamine is used in bronchial and dermal provocation, but it is rarely considered an environmental risk factor in allergic disease. Because bed bugs defecate large amounts of histamine as a component of their aggregation pheromone, we sought to determine if histamine accumulates in household dust in bed bug infested homes, and the effects of bed bug eradication with spatial heat on histamine levels in dust. We collected dust in homes and analyzed for histamine before, and up to three months after bed bug eradication. Histamine levels in bed bug infested homes were remarkably high (mean = 54.6±18.9 μg/100 mg of sieved household dust) and significantly higher than in control homes not infested with bed bugs (mean emergent contaminant and pose a serious health risk in the indoor environment.

3,5-Bis(ethynyl)pyridine and 2,6-bis(ethynyl)pyridine spanning two Fe(Cp*)(dppe) units: role of the nitrogen atom on the electronic and magnetic couplings.

Science.gov (United States)

Costuas, Karine; Cador, Olivier; Justaud, Frédéric; Le Stang, Sylvie; Paul, Frédéric; Monari, Antonio; Evangelisti, Stefano; Toupet, Loï C; Lapinte, Claude; Halet, Jean-François

2011-12-19

The role of the nitrogen atom on the electronic and magnetic couplings of the mono-oxidized and bi-oxidized pyridine-containing complex models [2,6-{Cp(dpe)Fe-C≡C-}(2)(NC(5)H(3))](n+) and [3,5-{Cp(dpe)Fe-C≡C-}(2)(NC(5)H(3))](n+) is theoretically tackled with the aid of density-functional theory (DFT) and multireference configuration interaction (MR-CI) calculations. Results are analyzed and compared to those obtained for the reference complex [1,3-{Cp*(dppe)Fe-C≡C-)}(2)(C(6)H(4))](n+). The mono-oxidized species show an interesting behavior at the borderline between spin localization and delocalization and one through-bond communication path among the two involving the central ring, is favored. Investigation of the spin state of the dicationic complexes indicates ferromagnetic coupling, which can differ in magnitude from one complex to the other. Very importantly, electronic and magnetic properties of these species strongly depend not only upon the location of the nitrogen atom in the ring versus that of the organometallic end-groups but also upon the architectural arrangement of one terminus, with respect to the other and/or vis-à-vis the central ring. To help validate the theoretical results, the related families of compounds [1,3-{Cp*(dppe)Fe-C≡C-)}(2)(C(6)H(4))](n+), [2,6-{Cp*(dppe)Fe-C≡C-}(2)(NC(5)H(3))](n+), [3,5-{Cp*(dppe)Fe-C≡C-}(2)(NC(5)H(3))](n+) (n = 0-2) were experimentally synthesized and characterized. Electrochemical, spectroscopic (infrared (IR), Mössbauer), electronic (near-infrared (NIR)), and magnetic properties (electron paramagnetic resonance (EPR), superconducting quantum interference device (SQUID)) are discussed and interpreted in the light of the theoretical data. The set of data obtained allows for many strong conclusions to be drawn. A N atom in the long branch increases the ferromagnetic interaction between the two Fe(III) spin carriers (J > 500 cm(-1)), whereas, when placed in the short branch, it dramatically reduces the

Le dosage de l'histamine plasmatique lors de réactions anaphylactoïdes chez le sujet anesthésié: Influence des méthodes de prélèvement et de la préparation du plasma sur l'histaminémie mesurée [Plasma histamine assay in anaphylactoid reactions of the anesthetized subject. Effects of collection methods and plasma preparation on measured histamine

OpenAIRE

Lorenz, Wilfried; Neugebauer, E.; Schmal, A.

1982-01-01

Plasma histamine assay in man is indicated for the diagnosis of histamine release, as well as the elucidation of the mechanisms of adverse drug reactions, and the identification of clinical situations in anaesthesia and surgery where a pathological plasma histamine level may occur. Normal and pathological plasma histamine levels vary considerably in the literature. Data from various studies, especially one involving 300 patients in Heidelberg (G.F.R.), allow us to define the normal range for ...

Major advances in the development of histamine H4 receptor ligands.

Science.gov (United States)

Smits, Rogier A; Leurs, Rob; de Esch, Iwan J P

2009-08-01

The search for new and potent histamine H4 receptor ligands is leading to a steadily increasing number of scientific publications and patent applications. Several interesting and structurally diverse compounds have been found, but fierce IP competition for a preferred 2-aminopyrimidine scaffold is becoming apparent. Recent investigations into the role of the histamine H(4)R in (patho)physiology and the use of H4R ligands in in vivo disease models reveal enormous potential in the field of inflammation and allergy, among others. The development of ligands that display activity at two or more histamine receptor (HR) subtypes is another clinical opportunity that is currently being explored. Taken together, the histamine H4R field is gearing up for clinical studies and has the potential to deliver another generation of blockbuster drugs.

Targeting of histamine producing cells by EGCG: a green dart against inflammation?

Science.gov (United States)

Melgarejo, Esther; Medina, Miguel Angel; Sánchez-Jiménez, Francisca; Urdiales, José Luis

2010-09-01

The human body is made of some 250 different cell types. From them, only a small subset of cell types is able to produce histamine. They include some neurons, enterochromaffin-like cells, gastrin-containing cells, mast cells, basophils, and monocytes/macrophages, among others. In spite of the reduced number of these histamine-producing cell types, they are involved in very different physiological processes. Their deregulation is related with many highly prevalent, as well as emergent and rare diseases, mainly those described as inflammation-dependent pathologies, including mastocytosis, basophilic leukemia, gastric ulcer, Crohn disease, and other inflammatory bowel diseases. Furthermore, oncogenic transformation switches some non-histamine-producing cells to a histamine producing phenotype. This is the case of melanoma, small cell lung carcinoma, and several types of neuroendocrine tumors. The bioactive compound epigallocatechin-3-gallate (EGCG), a major component of green tea, has been shown to target histamine-producing cells producing great alterations in their behavior, with relevant effects on their proliferative potential, as well as their adhesion, migration, and invasion potentials. In fact, EGCG has been shown to have potent anti-inflammatory, anti-tumoral, and anti-angiogenic effects and to be a potent inhibitor of the histamine-producing enzyme, histidine decarboxylase. Herein, we review the many specific effects of EGCG on concrete molecular targets of histamine-producing cells and discuss the relevance of these data to support the potential therapeutic interest of this compound to treat inflammation-dependent diseases.

Pharmacological Characterization of 5-Substituted 1-[(2,3-dihydro-1-benzofuran-2-ylmethyl]piperazines: Novel Antagonists for the Histamine H3 and H4 Receptors with Anti-inflammatory Potential

Directory of Open Access Journals (Sweden)

Michelle F. Corrêa

2017-11-01

Full Text Available The histamine receptors (HRs are traditional G protein-coupled receptors of extensive therapeutic interest. Recently, H3R and H4R subtypes have been targeted in drug discovery projects for inflammation, asthma, pain, cancer, Parkinson’s, and Alzheimer’s diseases, which includes searches for dual acting H3R/H4R ligands. In the present work, nine 1-[(2,3-dihydro-1-benzofuran-2-ylmethyl]piperazine (LINS01 series molecules were synthesized and evaluated as H3R and H4R ligands. Our data show that the N-allyl-substituted compound LINS01004 bears the highest affinity for H3R (pKi 6.40, while the chlorinated compound LINS01007 has moderate affinity for H4R (pKi 6.06. In addition, BRET assays to assess the functional activity of Gi1 coupling indicate that all compounds have no intrinsic activity and act as antagonists of these receptors. Drug-likeness assessment indicated these molecules are promising leads for further improvements. In vivo evaluation of compounds LINS01005 and LINS01007 in a mouse model of asthma showed a better anti-inflammatory activity of LINS01007 (3 g/kg than the previously tested compound LINS01005. This is the first report with functional data of these compounds in HRs, and our results also show the potential of their applications as anti-inflammatory.

Presynaptic localization of histamine H3-receptors in rat brain

International Nuclear Information System (INIS)

Fujimoto, K.; Mizuguchi, H.; Fukui, H.; Wada, H.

1991-01-01

The localization of histamine H3-receptors in subcellular fractions from the rat brain was examined in a [3H] (R) alpha-methylhistamine binding assay and compared with those of histamine H1- and adrenaline alpha 1- and alpha 2-receptors. Major [3H](R) alpha-methylhistamine binding sites with increased specific activities ([3H]ligand binding vs. protein amount) were recovered from the P2 fraction by differential centrifugation. Minor [3H](R)alpha-methylhistamine binding sites with increased specific activities were also detected in the P3 fraction. Further subfractionation of the P2 fraction by discontinuous sucrose density gradient centrifugation showed major recoveries of [3H](R)alpha-methylhistamine binding in myelin (MYE) and synaptic plasma membrane (SPM) fractions. A further increase in specific activity was observed in the MYE fraction, but the SPM fraction showed no significant increase in specific activity. Adrenaline alpha 2-receptors, the pre-synaptic autoreceptors, in a [3H] yohimbine binding assay showed distribution patterns similar to histamine H3-receptors. On the other hand, post-synaptic histamine H1- and adrenaline alpha 1-receptors were closely localized and distributed mainly in the SPM fraction with increased specific activity. Only a negligible amount was recovered in the MYE fraction, unlike the histamine H3- and adrenaline alpha 2-receptors

Comparison of in vitro histamine release by ionic and nonionic radiographyic contrast media

International Nuclear Information System (INIS)

Faraj, B.A.; Martin, L.G.

1989-01-01

This paper discusses a study whose results showed that in 53 hospitalized patients undergoing cardiovascular catheterization, incubation of their blood samples with varying concentrations of an ionic contrast medium (Angiovist-370, 60--631 mM) induced a significant (P < .005) amount of histamine release from whole blood (3.5%--10%), as compared with the histamine release following incubation with a nonionic contrast medium. Data suggest that the use of nonionic contrast media may induce minimal histamine release and thereby involve less patient risk from the histamine-mediated allergic and hemodynamic side effects associated with radiographic contrast media procedures

Extended-gate organic field-effect transistor for the detection of histamine in water

Science.gov (United States)

Minamiki, Tsukuru; Minami, Tsuyoshi; Yokoyama, Daisuke; Fukuda, Kenjiro; Kumaki, Daisuke; Tokito, Shizuo

2015-04-01

As part of our ongoing research program to develop health care sensors based on organic field-effect transistor (OFET) devices, we have attempted to detect histamine using an extended-gate OFET. Histamine is found in spoiled or decayed fish, and causes foodborne illness known as scombroid food poisoning. The new OFET device possesses an extended gate functionalized by carboxyalkanethiol that can interact with histamine. As a result, we have succeeded in detecting histamine in water through a shift in OFET threshold voltage. This result indicates the potential utility of the designed OFET devices in food freshness sensing.

Implication of prostaglandins and histamine H1 and H2 receptors in radiation-induced temperature responses of rats

International Nuclear Information System (INIS)

Kandasamy, S.B.; Hunt, W.A.; Mickley, G.A.

1988-01-01

Exposure of rats to 1-15 Gy gamma radiation ( 60 Co) induced hyperthermia, whereas 20-200 Gy induced hypothermia. Exposure either to the head or to the whole body to 10 Gy induced hyperthermia, while body-only exposure produced hypothermia. This observation indicates that radiation-induced fever is a result of a direct effect on the brain. The hyperthermia due to 10 Gy was significantly attenuated by the pre- or post-treatment with a cyclooxygenase inhibitor, indomethacin. Hyperthermia was also altered by the central administration of a mu-receptor antagonist naloxone but only at low doses of radiation. These findings suggest that radiation-induced hyperthermia may be mediated through the synthesis and release of prostaglandins in the brain and to a lesser extent to the release of endogenous opioid peptides. The release of histamine acting on H1 and H2 receptors may be involved in radiation-induced hypothermia, since both the H1 receptor antagonist, mepyramine, and H2 receptor antagonist, cimetidine, antagonized the hypothermia. The results of these studies suggest that the release of neurohumoral substances induced by exposure to ionizing radiation is dose dependent and has different consequences on physiological processes such as the regulation of body temperature. Furthermore, the antagonism of radiation-induced hyperthermia by indomethacin may have potential therapeutic implications in the treatment of fever resulting from accidental irradiations

Cold urticaria. Dissociation of cold-evoked histamine release and urticara following cold challenge.

Science.gov (United States)

Keahey, T M; Greaves, M W

1980-02-01

Nine patients with acquired cold urticaria were studied to assess the effects of beta-adrenergic agents, xanthines, and corticosteroids on cold-evoked histamine release from skin in vivo. The patients, in all of whom an immediate urticarial response developed after cooling of the forearm, demonstrated release of histamine into the venous blood draining that forearm. Following treatment with aminophylline and albuterol in combination or prednisone alone, suppression of histamine release occurred in all but one patient. In some patients, this was accompanied by a subjective diminution in pruritus or buring, but there was no significant improvement in the ensuing edema or erythema. In one patient, total suppression of histamine release was achieved without any effect on whealing and erythema in response to cold challenge. Our results suggest that histamine is not central to the pathogenesis of vascular changes in acquired cold urticaria.

Measurement of histamine release from human lung tissue ex vivo by microdialysis technique

DEFF Research Database (Denmark)

Nissen, Dan; Petersen, Lars Jelstrup; Nolte, H

1998-01-01

OBJECTIVE AND DESIGN: Currently no method is available for measurement of mediator release from intact human lung. In this study, a microdialysis technique was used to measure histamine release from mast cells in human lung tissue ex vivo. MATERIAL: Microdialysis fibers of 216 microm were inserted...... responses were observed but data could be reproduced within individual donors. Monocyte chemoattractant protein-1, a potent basophil secretagogue, did not induce histamine release in lung tissue which indicated mast cells to be the histamine source. Substance P did not release histamine in the lung tissue....... CONCLUSIONS: The microdialysis technique allowed measurements of histamine release from mast cells in intact lung ex vivo. The method may prove useful since a number of experiments can be performed in a few hours in intact lung tissue without any dispersion or enzymatic treatment....

Inhibition of basophil histamine release by gangliosides. Further studies on the significance of cell membrane sialic acid in the histamine release process

DEFF Research Database (Denmark)

Jensen, C; Norn, S; Thastrup, Ole

1987-01-01

with the glucolipid mixture increased the sialic acid content of the cells, and this increase was attributed to an insertion of gangliosides into the cell membrane. The inhibition of histamine release was abolished by increasing the calcium concentration, which substantiates our previous findings that cell membrane......Histamine release from human basophils was inhibited by preincubation of the cells with a glucolipid mixture containing sialic acid-containing gangliosides. This was true for histamine release induced by anti-IgE, Concanavalin A and the calcium ionophore A23187, whereas the release induced by S....... aureus Wood 46 was not affected. It was demonstrated that the inhibitory capacity of the glucolipid mixture could be attributed to the content of gangliosides, since no inhibition was obtained with cerebrosides or with gangliosides from which sialic acid was removed. Preincubation of the cells...

Histamine H3 receptors and its antagonism as a novel mechanism for antipsychotic effect: a current preclinical & clinical perspective.

Science.gov (United States)

Mahmood, Danish

2016-10-01

Histamine H 3 receptors are present as autoreceptors on histaminergic neurons and as heteroreceptors on nonhistaminergic neurones. They control the release and synthesis of histamine and several other key neurotransmitters in the brain. H 3 antagonism may be a novel approach to develop a new class of antipsychotic medications given the gathering evidence reporting therapeutic efficacy in several central nervous system disorders. Several medications such as cariprazine, lurasidone, LY214002, bexarotene, rasagiline, raloxifene, BL-1020 and ITI-070 are being developed to treat the negative symptoms and cognitive impairments of schizophrenia. These medications works through diverse mechanisms which include agonism at metabotropic glutamate receptor (mGluR2/3), partial agonism at dopamine D 2 , D 3 and serotonin 5-HT 1A receptors, antagonism at D 2 , 5-HT 2A, 5-HT 2B and 5-HT 7 receptors, combined dopamine antagonism with GABA agonist activity, inhibition of monoamine oxidase-B, modulation of oestrogen receptor, and activation of nuclear retinoid X receptor. However, still specific safe therapy for psychosis remains at large. Schizophrenia is a severe neuropsychiatric disorder result both from hyper- and hypo-dopaminergic transmission causing positive and negative symptoms, respectively. Pharmacological stimulation of dopamine release in the prefrontal cortex has been a viable approach in treating negative symptoms and cognitive deficits of schizophrenia symptoms that are currently not well treated and continue to represent significant unmet medical challenges. Administration of H 3 antagonists/inverse agonists increase extracellular dopamine concentrations in rat prefrontal cortex, but not in the striatum suggesting that antagonism via H 3 receptor may be a potential target for treating negative symptoms and cognitive deficits associated with schizophrenia. Further, insights are emerging into the potential role of histamine H 3 receptors as a target of antiobesity

Glucagon Effects on 3H-Histamine Uptake by the Isolated Guinea-Pig Heart during Anaphylaxis

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Mirko Rosic

2014-01-01

Full Text Available We estimated the influence of acute glucagon applications on 3H-histamine uptake by the isolated guinea-pig heart, during a single 3H-histamine passage through the coronary circulation, before and during anaphylaxis, and the influence of glucagon on level of histamine, NO, O2-, and H2O2 in the venous effluent during anaphylaxis. Before anaphylaxis, glucagon pretreatment does not change 3H-histamine Umax and the level of endogenous histamine. At the same time, in the presence of glucagon, 3H-histamine Unet is increased and backflux is decreased when compared to the corresponding values in the absence of glucagon. During anaphylaxis, in the presence of glucagon, the values of 3H-histamine Umax and Unet are significantly higher and backflux is significantly lower in the presence of glucagon when compared to the corresponding values in the absence of glucagon. The level of endogenous histamine during anaphylaxis in the presence of glucagon (6.9–7.38 × 10−8 μM is significantly lower than the histamine level in the absence of glucagon (10.35–10.45 × 10−8 μM. Glucagon pretreatment leads to a significant increase in NO release (5.69 nmol/mL in comparison with the period before glucagon administration (2.49 nmol/mL. Then, in the presence of glucagon, O2- level fails to increase during anaphylaxis. Also, our results show no significant differences in H2O2 levels before, during, and after anaphylaxis in the presence of glucagon, but these values are significantly lower than the corresponding values in the absence of glucagon. In conclusion, our results show that glucagon increases NO release and prevents the increased release of free radicals during anaphylaxis, and decreases histamine level in the venous effluent during cardiac anaphylaxis, which may be a consequence of decreased histamine release and/or intensified histamine capturing by the heart during anaphylaxis.

Glucagon effects on 3H-histamine uptake by the isolated guinea-pig heart during anaphylaxis.

Science.gov (United States)

Rosic, Mirko; Parodi, Oberdan; Jakovljevic, Vladimir; Colic, Maja; Zivkovic, Vladimir; Jokovic, Vuk; Pantovic, Suzana

2014-01-01

We estimated the influence of acute glucagon applications on (3)H-histamine uptake by the isolated guinea-pig heart, during a single (3)H-histamine passage through the coronary circulation, before and during anaphylaxis, and the influence of glucagon on level of histamine, NO, O2 (-), and H2O2 in the venous effluent during anaphylaxis. Before anaphylaxis, glucagon pretreatment does not change (3)H-histamine Umax and the level of endogenous histamine. At the same time, in the presence of glucagon, (3)H-histamine Unet is increased and backflux is decreased when compared to the corresponding values in the absence of glucagon. During anaphylaxis, in the presence of glucagon, the values of (3)H-histamine Umax and Unet are significantly higher and backflux is significantly lower in the presence of glucagon when compared to the corresponding values in the absence of glucagon. The level of endogenous histamine during anaphylaxis in the presence of glucagon (6.9-7.38 × 10(-8) μM) is significantly lower than the histamine level in the absence of glucagon (10.35-10.45 × 10(-8) μM). Glucagon pretreatment leads to a significant increase in NO release (5.69 nmol/mL) in comparison with the period before glucagon administration (2.49 nmol/mL). Then, in the presence of glucagon, O2 (-) level fails to increase during anaphylaxis. Also, our results show no significant differences in H2O2 levels before, during, and after anaphylaxis in the presence of glucagon, but these values are significantly lower than the corresponding values in the absence of glucagon. In conclusion, our results show that glucagon increases NO release and prevents the increased release of free radicals during anaphylaxis, and decreases histamine level in the venous effluent during cardiac anaphylaxis, which may be a consequence of decreased histamine release and/or intensified histamine capturing by the heart during anaphylaxis.

Brain Histamine -Methyltransferase as a Possible Target of Treatment for Methamphetamine Overdose

Directory of Open Access Journals (Sweden)

Junichi Kitanaka

2016-01-01

Full Text Available Stereotypical behaviors induced by methamphetamine (METH overdose are one of the overt symptoms of METH abuse, which can be easily assessed in animal models. Currently, there is no successful treatment for METH overdose. There is increasing evidence that elevated levels of brain histamine can attenuate METH-induced behavioral abnormalities, which might therefore constitute a novel therapeutic treatment for METH abuse and METH overdose. In mammals, histamine N -methyltransferase (HMT is the sole enzyme responsible for degrading histamine in the brain. Metoprine, one of the most potent HMT inhibitors, can cross the blood-brain barrier and increase brain histamine levels by inhibiting HMT. Consequently, this compound can be a candidate for a prototype of drugs for the treatment of METH overdose.

The effect of tartrazine on histamine release from rat peritoneal mast cells.

Science.gov (United States)

Safford, R J; Goodwin, B F

1984-01-01

The release of histamine from purified rat peritoneal mast cells induced by specific antigen (egg albumin), compound 48/80 and calcium ionophore A23187 was modified by tartrazine. Histamine release induced by 48/80 and antigen was inhibited by the presence of 10(-5) to 10(-2)M tartrazine. The inhibitory effect on egg albumin induced histamine release was maximal when the tartrazine was added simultaneously with egg albumin, and was reduced by increased preincubation of the cells with tartrazine. Tartrazine had a small inhibitory effect on ionophore induced release at high concentrations, but augmented histamine release at tartrazine concentrations of 10(-3) and 10(-4)M. Augmentation of ionophore induced release was maximal at between 0-5 min preincubation of the cells with tartrazine.

Bacteria-induced histamine release from human bronchoalveolar cells and blood leukocytes

DEFF Research Database (Denmark)

Clementsen, P; Milman, N; Struve-Christensen, E

1991-01-01

23187 resulted in histamine release. S. aureus-induced histamine release from basophils was examined in leukocyte suspensions obtained from the same individuals, and in all experiments release was found. The dose-response curves were similar to those obtained with BAL cells. The bacteria...

Characteristics of the mouse genomic histamine H1 receptor gene

Energy Technology Data Exchange (ETDEWEB)

Inoue, Isao; Taniuchi, Ichiro; Kitamura, Daisuke [Kyushu Univ., Fukuoka (Japan)] [and others

1996-08-15

We report here the molecular cloning of a mouse histamine H1 receptor gene. The protein deduced from the nucleotide sequence is composed of 488 amino acid residues with characteristic properties of GTP binding protein-coupled receptors. Our results suggest that the mouse histamine H1 receptor gene is a single locus, and no related sequences were detected. Interspecific backcross analysis indicated that the mouse histamine H1 receptor gene (Hrh1) is located in the central region of mouse Chromosome 6 linked to microphthalmia (Mitfmi), ras-related fibrosarcoma oncogene 1 (Raf1), and ret proto-oncogene (Ret) in a region of homology with human chromosome 3p. 12 refs., 3 figs.

Novel chalcone-based fluorescent human histamine H3 receptor ligands as pharmacological tools

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Holger eStark

2012-03-01

Full Text Available Novel fluorescent chalcone-based ligands at human histamine H3 receptors (hH3R have been designed, synthesized and characterized. Compounds described are non-imidazole analogues of ciproxifan with a tetralone motif. Tetralones as chemical precursors and related fluorescent chalcones exhibit affinities at hH3R in the same concentration range like that of the reference antagonist ciproxifan (hH3R pKi value of 7.2. Fluorescence characterization of our novel ligands shows emission maxima about 570 nm for yellow fluorescent chalcones and ≥600 nm for the red fluorescent derivatives. Interferences to cellular autofluorescence could be excluded. All synthesized chalcone compounds could be taken to visualize hH3R proteins in stably transfected HEK-293 cells using confocal laser scanning fluorescence microscopy. These novel fluorescent ligands possess high potential to be used as pharmacological tools for hH3R visualization in different tissues.

Validation of the method spectrophotometer in the histamine determination in fresh tuna (Thunnus Tunna)

International Nuclear Information System (INIS)

Chacon Silva, F.

1998-01-01

The objective of this study was to validate the spectrophotometer method described by Bateman et al. (1994) for the histamine determination in fresh tuna (Thunnus Tunna) and to evaluate the histamine concentration in samples of fresh tuna. To fulfill the recently exposed objectives, the figures of merit were determined like they are it: recovery limits of detection, sensibility and repetitive of the method spectrophotometry and applied the analysis at twenty samples of fresh tuna for copy of the Metropolitan area and three sample like reference of fresh tuna stored 4 degree centigrade by 15 days. The histamine recovery you determines enriching seven ours of fresh tuna with histamine to two levels different 0.613 mg/L and 2.21 mg/L. three samples were left without enriching and you subtract the average to the native histamine. You determines the one it limits of detection using the standard deviation to three levels of concentration of histamine 1.37 mg/L, 2.22 mg/L and 3.22 mg/L, the minimum quantity of hi stamina that you can determine for the method spectrophotometry settling down. The repetitive you determines using the standard deviation for 100 among the average of the histamine values, in seven you replies independent of the same sample. You determines the histamine content, in the fresh tuna Thunnus Tunna of the expends of the Metropolitan Area and in samples of reference stored 4 degrees centigrade by 15 days [es

Liberation of plasma histamine after application of non-ionic contrast media

International Nuclear Information System (INIS)

Weiss, H.D.; Jansen, O.; Schallock, J.

1989-01-01

In 94 patients the levels of plasmahistamine have been measured after application of three non-ionic contrast media (Iopromid, Iopamidol, Iohexol) and after application of blood-isotonic saline solution. A significant liberation of histamine could be observed after administration of contrast media and also after administration of saline solution. Neither between the three nonionic contrast media nor between the contrast media and the saline solution significant differences could be measured. Administering contrast media after subsequently saline solution the levels of histamine were lower than in case of pure contrast media application. A psychogen induced histamine liberation is discussed. (orig.) [de

PCR detection and identification of histamine-forming bacteria in filleted tuna fish samples.

Science.gov (United States)

Ferrario, Chiara; Pegollo, Chiara; Ricci, Giovanni; Borgo, Francesca; Fortina, M Grazia

2012-02-01

Total of 14 filleted yellowfin tuna fish (Thunnus albacares) sold in wholesale fish market and supermarkets in Milan, Italy, were purchased and tested to determine microbial count, histamine level, histamine-forming bacteria, and their ability to produce histamine in culture broth. Although histamine level was less than 10 ppm, many samples showed high total viable bacterial and enterobacterial counts that reached dangerous levels after temperature abuse for short periods of time. A PCR assay targeting a 709-bp fragment of the histidine decarboxylase gene (hdc) revealed that 30.5% of the 141 enteric bacteria isolated from samples were positive and potentially able to produce histamine. The hdc positive strains were mainly isolated from fish bought at wholesale fish market, where we observed several possible risk factors, such as handling in poor and non-refrigerated conditions during fillet preparation. These positive strains were identified as Citrobacter koseri/Enterobacter spp. and Morganella morganii, by 16S/23S rRNA internal transcribed spacer amplification and 16S rRNA sequence analysis. The strains showed a variable ability of histamine production, with Morganella morganii being the most active histamine-producing species. A direct DNA extraction from fish and a PCR targeting the hdc gene showed a high degree of concordance with the results obtained through microbiological and chemical analyses, and could aid in the prompt detection of potentially contaminated fish products, before histamine accumulates. The use of methods for the early and rapid detection of bacteria producing biogenic amines is important for preventing accumulation of these toxic substances in food products. In this study, we used a molecular approach for the detection of histamine-forming bacteria in fish. PCR-based methods require expensive equipment and a high degree of training for the user, but are fast (marketing and can be used in the investigation of risk reduction strategies. �

Histamine Induces Bovine Rumen Epithelial Cell Inflammatory Response via NF-κB Pathway

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Xudong Sun

2017-06-01

Full Text Available Background/Aims: Subacute ruminal acidosis (SARA is a common disease in high-producing lactating cows. Rumenitis is the initial insult of SARA and is associated with the high concentrations of histamine produced in the rumen of dairy cows during SARA. However, the exact mechanism remains unclear. The objective of the current study is to investigate whether histamine induces inflammation of rumen epithelial cells and the underlying mechanism of this process. Methods: Bovine rumen epithelial cells were cultured and treated with different concentrations of histamine and pyrrolidine dithiocarbamate (PDTC, an NF-κB inhibitor cultured in different pH medium (pH 7.2 or 5.5. qRT-PCR, Western-blotting, ELISA and immunocytofluorescence were used to evaluate whether histamine activated the NF-κB pathway and inflammatory cytokines. Results: The results showed that histamine significantly increased the activity of IKK β and the phosphorylation levels of IκB α, as well as upregulated the mRNA and protein expression levels of NF-κB p65 in the rumen epithelial cells cultured in neutral (pH=7.2 and acidic (pH=5.5 medium. Furthermore, histamine treatment also significantly increased the transcriptional activity of NF-κB p65. High expression and transcriptional activity of NF-κB p65 significantly increased the mRNA expressions and concentrations of inflammatory cytokines, tumor necrosis factor alpha (TNF-α, interleukin 6 (IL-6 and interleukin 1 beta (IL-1β, thereby inducing the inflammatory response in bovine rumen epithelial cells. However, inhibition of NF-κB p65 by PDTC significantly decreased the expressions and concentrations of the inflammatory cytokines induced by histamine in the rumen epithelial cells cultured in the neutral and acidic medium. Conclusion: The present data indicate that histamine induces the inflammatory response of bovine rumen epithelial cells through the NF-κB pathway.

Early and late histamine release induced by albumin, hetastarch and polygeline: some unexpected findings.

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Celik, I; Duda, D; Stinner, B; Kimura, K; Gajek, H; Lorenz, W

2003-10-01

The perioperative use of colloidal plasma substitutes is still under discussion. We therefore conducted a prospective randomised study with three commonly used plasma substitutes to examine their histamine releasing effects in 21 volunteers. MATERIAL OR SUBJETS: 21 male volunteers were enrolled in this prospective, randomised, controlled clinical study. Endpoints were the incidence of early and late histamine release and the time course of the release kinetics. Normovolemic hemodilution technique was used with hydroxyethyl starch (n = 6), human albumin (n = 6) and polygeline (n = 9). Measurement and observation period was 240 min after the start of the plasma substitute infusion. Heart rate, blood pressure, SaO(2), clinical symptoms/signs and plasma histamine were measured during the observation period. The incidence of histamine release over the whole observation period in all three groups was 100%. Histamine release occurred frequently in all three groups until 30 min (50%-78%) and up to 240 min (late release reaction: 67%-83%) after the start of infusion. Surprisingly even hydroxyethyl starch, which is regarded as a generally safe and effective plasma substitute, caused high incidences of late histamine release (67%). Histamine release is a well known side effect of polygeline and - to a lesser extent - also of albumin, but was a novel finding for hydroxyethyl starch. We demonstrated for the first time histamine releasing effects of hydroxyethyl starch over a long period of time after administration. This perioperatively and for intensive care possibly relevant finding should make clinicians aware of late side effects not yet connected with the clinical use of these colloidal plasma substitutes.

Effect of terfenadine on nasal, eustachian tube, and pulmonary function after provocative intranasal histamine challenge.

Science.gov (United States)

Skoner, D P; Doyle, W J; Boehm, S; Fireman, P

1991-12-01

Previous studies have documented that intranasal histamine challenge results in nasal and eustachian tube obstruction (ETO) in human volunteers. The purpose of the present study was to assess the effect of pretreatment with terfenadine, a nonsedating antihistamine on the pathophysiologic consequences of intranasal histamine challenge. Fifteen subjects with allergic rhinitis were challenged intranasally with saline and increasing histamine doses (0.01, 0.1, 0.5, 1.0, 5.0, and 10.0 mg) before pretreatment (baseline) and after 1 week of pretreatment with terfenadine, 60 mg b.i.d., terfenadine, 120 mg b.i.d., and placebo. Nasal conductance as measured by posterior rhinomanometry showed a dose-dependent, monotonic decrease following sequential administration of the histamine solutions, but there were no apparent differences in the average responses among the four challenge sessions. The frequency of ETO after histamine challenge was decreased by pretreatment with both doses of terfenadine, although this was not significant. Histamine-induced sneezing and rhinorrhea, but not congestion, were significantly reduced by terfenadine pretreatment. There was no evidence of extension of the histamine effects to the lower airway. The results of the present study suggest that terfenadine, a nonsedating antihistamine, had a favorable effect on sneezing and rhinorrhea after provocative intranasal histamine challenge, but did not significantly attenuate the subjective or objective nasal and ET obstructive responses.

BF2.649 [1-{3-[3-(4-Chlorophenyl)propoxy]propyl}piperidine, hydrochloride], a nonimidazole inverse agonist/antagonist at the human histamine H3 receptor: Preclinical pharmacology.

Science.gov (United States)

Ligneau, X; Perrin, D; Landais, L; Camelin, J-C; Calmels, T P G; Berrebi-Bertrand, I; Lecomte, J-M; Parmentier, R; Anaclet, C; Lin, J-S; Bertaina-Anglade, V; la Rochelle, C Drieu; d'Aniello, F; Rouleau, A; Gbahou, F; Arrang, J-M; Ganellin, C R; Stark, H; Schunack, W; Schwartz, J-C

2007-01-01

Histamine H3 receptor inverse agonists are known to enhance the activity of histaminergic neurons in brain and thereby promote vigilance and cognition. 1-{3-[3-(4-Chlorophenyl)propoxy]propyl}piperidine, hydrochloride (BF2.649) is a novel, potent, and selective nonimidazole inverse agonist at the recombinant human H3 receptor. On the stimulation of guanosine 5'-O-(3-[35S]thio)triphosphate binding to this receptor, BF2.649 behaved as a competitive antagonist with a Ki value of 0.16 nM and as an inverse agonist with an EC50 value of 1.5 nM and an intrinsic activity approximately 50% higher than that of ciproxifan. Its in vitro potency was approximately 6 times lower at the rodent receptor. In mice, the oral bioavailability coefficient, i.e., the ratio of plasma areas under the curve after oral and i.v. administrations, respectively, was 84%. BF2.649 dose dependently enhanced tele-methylhistamine levels in mouse brain, an index of histaminergic neuron activity, with an ED50 value of 1.6 mg/kg p.o., a response that persisted after repeated administrations for 17 days. In rats, the drug enhanced dopamine and acetylcholine levels in microdialysates of the prefrontal cortex. In cats, it markedly enhanced wakefulness at the expense of sleep states and also enhanced fast cortical rhythms of the electroencephalogram, known to be associated with improved vigilance. On the two-trial object recognition test in mice, a promnesiant effect was shown regarding either scopolamine-induced or natural forgetting. These preclinical data suggest that BF2.649 is a valuable drug candidate to be developed in wakefulness or memory deficits and other cognitive disorders.

Relation between histamine release and dye permeability of pulmonary blood-air barrier in x-irradiated rat

Energy Technology Data Exchange (ETDEWEB)

Yamazaki, H [Kobe Univ. (Japan). School of Medicine

1976-04-01

The histamine-release kinetics and the influence of released histamine on the permeability of the pulmonary blood-air(BA) barrier during the early period after either whole-body or thoracic x irradiation of the rat were studied. Histamine contents of skin and lung of the irradiated rat decreased rapidly, reaching a minimum at 5 h, and this histamine depletion continued for at least 7 days. Conversely, in circulating blood histamine increased during the early period of 5 h and then decreased gradually. This early increase was linear up to 500R and then became saturated between 500 and 1,000R. Administration of polymixine B (5mg/100g body weight) to rats liberated histamine similarly. Rat sera containg histamine released soon after irradiation enhanced the capillary permeability of Evans blue(EB) in the guinea pig skin reaction, which was effectively countered by pretreatment of the guinea pig with anti-histaminic pyribenzamine (29..mu..g/100g body weight), but not by anti-serotonic chlorpromazine (0.3mg/100g body weight). Similarly, perhaps only the EB-bound serum albumin (EB-albumin), that was seen in alveolar perfusate, penetrated more through the pulmonary BA-barrier with increasing x-ray dose, in parallel with the increase in blood histamine. Pyribenzamine inhibited this effect effectively, but cysteamine (a radical scavenger) did so only partially. Thus, it seems possible that at soon after x irradiation the enhanced permeability of EB-albumin through the BA barrier of rat lung is due preferentially to the pharmacologic action of released histamine and subsidiarily to radiation damage to pulmonary cells.

Noxious heat and scratching decrease histamine-induced itch and skin blood flow.

Science.gov (United States)

Yosipovitch, Gil; Fast, Katharine; Bernhard, Jeffrey D

2005-12-01

The aim of this study was to assess the effect of thermal stimuli or distal scratching on skin blood flow and histamine-induced itch in healthy volunteers. Twenty-one healthy volunteers participated in the study. Baseline measurements of skin blood flow were obtained on the flexor aspect of the forearm. These measurements were compared with skin blood flow after various stimuli: heating the skin, cooling the skin, noxious cold 2 degrees C, noxious heat 49 degrees C, and scratching via a brush with controlled pressure. Afterwards histamine iontophoresis was performed and skin blood flow and itch intensity were measured immediately after the above-mentioned stimuli. Scratching reduced mean histamine-induced skin blood flow and itch intensity. Noxious heat pain increased basal skin blood flow but reduced histamine-induced maximal skin blood flow and itch intensity. Cold pain and cooling reduced itch intensity, but neither affected histamine-induced skin blood flow. Sub-noxious warming the skin did not affect the skin blood flow or itch intensity. These findings suggest that heat pain and scratching may inhibit itch through a neurogenic mechanism that also affects skin blood flow.

Increased release of histamine in patients with respiratory symptoms related to perfume.

Science.gov (United States)

Elberling, J; Skov, P S; Mosbech, H; Holst, H; Dirksen, A; Johansen, J D

2007-11-01

Environmental perfume exposure may cause respiratory symptoms. Individuals with asthma and perfume contact allergy report such symptoms more frequently than others. However, immunologic mechanisms have not been demonstrated and the symptoms are not associated with IgE-mediated allergy. The study aimed to investigate whether basophils from patients with respiratory symptoms related to perfume released more histamine in the presence of perfume as compared with healthy volunteers. Histamine release was measured by the glass fibre method. Blood was obtained from healthy volunteers (n=20) and patients with respiratory symptoms related to perfume (n=17) attending a dermatological outpatient clinic for patch testing. The effect of an international brand perfume was investigated using the basophil histamine release test with perfume. Furthermore, basophils from a healthy non-atopic donor were incubated with participant's sera and histamine release induced by perfume was measured. In both groups incremental perfume concentrations showed a positive and significant (Pperfume concentration, the basophils released significantly (PPerfume induces a dose-dependent non-IgE-mediated release of histamine from human peripheral blood basophils. Increased basophil reactivity to perfume was found in patients with respiratory symptoms related to perfume.

Desloratadine citrate disodium injection, a potent histamine H(1) receptor antagonist, inhibits chemokine production in ovalbumin-induced allergic rhinitis guinea pig model and histamine-induced human nasal epithelial cells via inhibiting the ERK1/2 and NF-kappa B signal cascades.

Science.gov (United States)

Chen, Meiling; Xu, Shuhong; Zhou, Peipei; He, Guangwei; Jie, Qiong; Wu, Yulin

2015-11-15

Chemokines have chemotactic properties on leukocyte subsets whose modulation plays a pivotal role in allergic inflammatory processes. Our present study was designed to investigate the anti-allergic and anti-inflammatory properties of desloratadine citrate disodium injection (DLC) and elucidate the molecular mechanisms of its anti-inflammatory properties. The anti-allergic effects of DLC were evaluated based on allergic symptoms, serological marker production and histological changes of the nasal mucosa in guinea pigs model of allergic rhinitis. The anti-inflammatory properties and molecular mechanisms of DLC were explored by studying the regulation of a set of chemokines and extracellular signal-regulated kinase (ERK)1/2 and nuclear factor-kappa B (NF-κB) pathways, after DLC treatment in guinea pigs model of allergic rhinitis in vivo and histamine-activated human nasal epithelial cells (HNECs) in vitro. In vivo model in guinea pigs, DLC alleviated the rhinitis symptoms, inhibited inflammatory cells infiltration in nasal lavage fluid (NLF) and histamine, monocyte chemotactic protein (MCP)-1, regulated on activation normal T cell expressed, and presumably secreted (RANTEs) and interleukin (IL)-8 release in sera and P-ERK1/2 and NF-κB activation in nasal mucosa. In vitro, DLC markedly inhibited histamine-induced production of MCP-1, RANTEs and IL-8 and suppressed c-Raf, mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) and ERK1/2 activation in HNECs. These results provide evidence that DLC possesses potent anti-allergic and anti-inflammatory properties. The mechanism of action underlying DLC in allergic inflammation appears to be inhibition of the phosphorylation of ERK1/2, in addition to blocking of the NF-κB pathway. Copyright © 2015 Elsevier B.V. All rights reserved.

Indian red scorpion venom-induced augmentation of cardio-respiratory reflexes and pulmonary edema involve the release of histamine.

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Dutta, Abhaya; Deshpande, Shripad B

2011-02-01

Pulmonary edema is a consistent feature of Mesobuthus tamulus (MBT) envenomation. Kinins, prostaglandins and other inflammatory mediators are implicated in it. Since, histamine also increases capillary permeability, this study was undertaken to evaluate whether MBT venom utilizes histamine to produce pulmonary edema and augmentation of cardio-respiratory reflexes evoked by phenylbiguanide (PBG). Blood pressure, respiratory excursions and ECG were recorded in urethane anaesthetized adult rats. Injection of PBG (10 μg/kg) produced apnoea, hypotension and bradycardia and the responses were augmented after exposure to venom (100 μg/kg). There was increased pulmonary water content in these animals. Pretreatment with pheniramine maleate (H₁ antagonist, 3 mg/kg) blocked both venom-induced augmentation of PBG response and pulmonary edema. In another series, compound 48/80 (mast cell depletor) was treated for 4 days then the PBG responses were elicited as before. At the end of the experiments, mast cells were counted from the peritoneal fluid. The venom-induced pulmonary edema and the augmentation of PBG reflex were not observed in compound 48/80 treated animals. Further, mast cells in the peritoneal fluid were absent in this group as compared to vehicle treated group (29 ± 7.9 cells/mm³). These observations indicate that venom-induced pulmonary edema and augmentation of PBG reflexe are mediated through mast cells by involving H₁ receptors. Copyright © 2010 Elsevier Ltd. All rights reserved.

Withdrawal of repeated morphine enhances histamine-induced scratching responses in mice.

Science.gov (United States)

Abe, Kenji; Kobayashi, Kanayo; Yoshino, Saori; Taguchi, Kyoji; Nojima, Hiroshi

2015-04-01

An itch is experientially well known that the scratching response of conditions such as atopic dermatitis is enhanced under psychological stress. Morphine is typical narcotic drug that induces a scratching response upon local application as an adverse drug reaction. Although long-term treatment with morphine will cause tolerance and dependence, morphine withdrawal can cause psychologically and physiologically stressful changes in humans. In this study, we evaluated the effects of morphine withdrawal on histamine-induced scratching behavior in mice. Administration of morphine with progressively increasing doses (10-50 mg/kg, i.p.) was performed for 5 consecutive days. At 3, 24, 48, and 72 hr after spontaneous withdrawal from the final morphine dose, histamine was intradermally injected into the rostral part of the back and then the number of bouts of scratching in 60 min was recorded and summed. We found that at 24 hr after morphine withdrawal there was a significant increase in histamine-induced scratching behavior. The spinal c-Fos positive cells were also significantly increased. The relative adrenal weight increased and the relative thymus weight decreased, both significantly. Moreover, the plasma corticosterone levels changed in parallel with the number of scratching bouts. These results suggest that morphine withdrawal induces a stressed state and enhances in histamine-induced scratching behavior. Increased reaction against histamine in the cervical vertebrae will participate in this stress-induced itch enhancement.

PENGGUNAAN EKSTRAK TEH HIJAU (Camellia sinensis) SEBAGAI PENGHAMBAT PEMBENTUKAN HISTAMIN PADA IKAN SEBELUM DIOLAH

OpenAIRE

Endang Sri Heruwati; Farida Ariyani; Radestya Triwibowo; Novalia Rachmawati; Irma Hermana

2009-01-01

Penelitian penggunaan ekstrak teh hijau (Camellia sinensis) sebagai penghambat pembentukan histamin pada ikan telah dilakukan. Ikan, terutama dari jenis skombroid, sangat rentan mengalami kerusakan karena terjadinya perubahan asam amino histidin yang terkandung dalam ikan menjadi senyawa histamin yang bersifat alergen, yang dikatalisasi oleh enzim histamin dekarboksilase (HDC). Teh hijau diketahui mengandung polifenol berupa senyawa epigalokatekingalat (EGCG) yang merupakan penghambat enzim H...

Absence of histamine-induced itch in the African naked mole-rat and "rescue" by Substance P.

Science.gov (United States)

Smith, Ewan St John; Blass, Gregory R C; Lewin, Gary R; Park, Thomas J

2010-05-24

Recent research has proposed a pathway in which sensory neurons expressing the capsaicin activated ion channel TRPV1 are required for histamine-induced itch and subsequent scratching behavior. We examined histamine-induced itch in the African naked mole-rat (Heterocephalus glaber) and found that although naked mole-rats display innate scratching behavior, histamine was unable to evoke increased scratching as is observed in most mouse strains. Using calcium imaging, we examined the histamine sensitivity of naked mole-rat dorsal root ganglia (DRG) neurons and identified a population of small diameter neurons activated by histamine, the majority of which are also capsaicin-sensitive. This suggested that naked mole-rat sensory neurons are activated by histamine, but that spinal dorsal horn processing of sensory information is not the same as in other rodents. We have previously shown that naked mole-rats naturally lack substance P (SP) in cutaneous C-fibers, but that the neurokinin-1 receptor is expressed in the superficial spinal cord. This led us to investigate if SP deficiency plays a role in the lack of histamine-induced scratching in this species. After intrathecal administration of SP into the spinal cord we observed robust scratching behavior in response to histamine injection. Our data therefore support a model in which TRPV1-expressing sensory neurons are important for histamine-induced itch. In addition, we demonstrate a requirement for active, SP-induced post-synaptic drive to enable histamine sensitive afferents to drive itch-related behavior in the naked mole-rat. These results illustrate that it is altered dorsal horn connectivity of nociceptors that underlies the lack of itch and pain-related behavior in the naked mole-rat.

Absence of histamine-induced itch in the African naked mole-rat and "rescue" by Substance P

Directory of Open Access Journals (Sweden)

Lewin Gary R

2010-05-01

Full Text Available Abstract Recent research has proposed a pathway in which sensory neurons expressing the capsaicin activated ion channel TRPV1 are required for histamine-induced itch and subsequent scratching behavior. We examined histamine-induced itch in the African naked mole-rat (Heterocephalus glaber and found that although naked mole-rats display innate scratching behavior, histamine was unable to evoke increased scratching as is observed in most mouse strains. Using calcium imaging, we examined the histamine sensitivity of naked mole-rat dorsal root ganglia (DRG neurons and identified a population of small diameter neurons activated by histamine, the majority of which are also capsaicin-sensitive. This suggested that naked mole-rat sensory neurons are activated by histamine, but that spinal dorsal horn processing of sensory information is not the same as in other rodents. We have previously shown that naked mole-rats naturally lack substance P (SP in cutaneous C-fibers, but that the neurokinin-1 receptor is expressed in the superficial spinal cord. This led us to investigate if SP deficiency plays a role in the lack of histamine-induced scratching in this species. After intrathecal administration of SP into the spinal cord we observed robust scratching behavior in response to histamine injection. Our data therefore support a model in which TRPV1-expressing sensory neurons are important for histamine-induced itch. In addition, we demonstrate a requirement for active, SP-induced post-synaptic drive to enable histamine sensitive afferents to drive itch-related behavior in the naked mole-rat. These results illustrate that it is altered dorsal horn connectivity of nociceptors that underlies the lack of itch and pain-related behavior in the naked mole-rat.

[A preliminary study on the role of substance P in histamine-nasal-spray-induced allergic conjunctivitis in guinea pigs].

Science.gov (United States)

Li, Tong; Zhao, Changqing

2015-10-01

To investigate the effect of the non adrenergic non cholinergic nerve (NANC) and substance P (SP) in allergic rhinoconjunctivitis by observing histamine nasal provocation induced conjunctivitis in guinea pigs. Forty male guinea pigs were randomly divided into five groups with each group consisting of eight guinea pigs. All anesthetized guinea pigs were exposed either to histamine (0.2%, 5 µl) (group B~E) or saline (5 µl, group A) via unilateral nostril. No pretreatment was done in group A and B while pretreatment was done in groups C~E through injection into the unilateral common carotid artery with cholinergic nerve inhibitor (atropine, 1 mg/kg, group C), cholinergic nerve inhibitor plus adrenergic nerve inhibitors (atropine, 1 mg/kg, phentolamine, 1 mg/kg plus Esmolol, 1 mg/kg, group D) and cholinergic nerve inhibitor, adrenergic nerve inhibitors plus SP receptor antagonist (the same treatment with group D plus D-SP 10(-6) mol/L, 1 µl/g, group E), respectively. To assess the ipsilateral conjunctival inflammatory reaction, conjunctiva leakage with Evans blue dye assessments and HE staining of conjunctival tissues were performed. The SP expression in ipsilateral conjunctival tissue in different groups of guinea pigs were assessed by immunofluorescence and RT-PCR. The activity of eosinophils was assessed by eosinophil major basic protein 1 (MBP1) with RT-PCR, meanwhile, the activity of mast cells was assessed by tryptase with RT-PCR. SPSS 17.0 software was used to analyze the data. At 30 min after nasal application of histamine, ipsilateral conjunctivitis was successfully induced as shown by the change of conjunctiva leakage and histology. The content of Evans blue in ipsilateral conjunctival tissue of group A~E was (13.78 ± 2.48), (29.62 ± 3.31), (19.03 ± 1.47), (18.42 ± 2.52), (14.83 ± 2.14) µg/ml, respectively. There was statistically significant difference between group A and B (t = -10.66, P 0.05). Histamine nasal provocation induced allergic

[Performance evaluation of a fluorescamine-HPLC method for determination of histamine in fish and fish products].

Science.gov (United States)

Kikuchi, Hiroyuki; Tsutsumi, Tomoaki; Matsuda, Rieko

2012-01-01

A method for the quantification of histamine in fish and fish products using tandem solid-phase extraction and fluorescence derivatization with fluorescamine was previously developed. In this study, we improved this analytical method to develop an official test method for quantification of histamine in fish and fish products, and performed a single laboratory study to validate it. Recovery tests of histamine from fillet (Thunnus obesus), and two fish products (fish sauce and salted and dried whole big-eye sardine) that were spiked at the level of 25 and 50 µg/g for T. obesus, and 50 and 100 µg/g for the two fish products, were carried out. The recoveries of histamine from the three samples tested were 88.8-99.6% with good repeatability (1.3-2.1%) and reproducibility (2.1-4.7%). Therefore, this method is acceptable for the quantification of histamine in fish and fish products. Moreover, surveillance of histamine content in food on the market was conducted using this method, and high levels of histamine were detected in some fish products.

A facile molecularly imprinted polymer-based fluorometric assay for detection of histamine

DEFF Research Database (Denmark)

Feng, Xiaotong; Ashley, Jon; Zhou, Tongchang

2018-01-01

urgently needed. In this paper, we developed a facile and cost-effective molecularly imprinted polymer (MIP)-based fluorometric assay to directly quantify histamine. Histamine-specific MIP nanoparticles (nanoMIPs) were synthesized using a modified solid-phase synthesis method. They were then immobilized...

Histamine Induces Bovine Rumen Epithelial Cell Inflammatory Response via NF-κB Pathway.

Science.gov (United States)

Sun, Xudong; Yuan, Xue; Chen, Liang; Wang, Tingting; Wang, Zhe; Sun, Guoquan; Li, Xiaobing; Li, Xinwei; Liu, Guowen

2017-01-01

Subacute ruminal acidosis (SARA) is a common disease in high-producing lactating cows. Rumenitis is the initial insult of SARA and is associated with the high concentrations of histamine produced in the rumen of dairy cows during SARA. However, the exact mechanism remains unclear. The objective of the current study is to investigate whether histamine induces inflammation of rumen epithelial cells and the underlying mechanism of this process. Bovine rumen epithelial cells were cultured and treated with different concentrations of histamine and pyrrolidine dithiocarbamate (PDTC, an NF-κB inhibitor) cultured in different pH medium (pH 7.2 or 5.5). qRT-PCR, Western-blotting, ELISA and immunocytofluorescence were used to evaluate whether histamine activated the NF-κB pathway and inflammatory cytokines. The results showed that histamine significantly increased the activity of IKK β and the phosphorylation levels of IκB α, as well as upregulated the mRNA and protein expression levels of NF-κB p65 in the rumen epithelial cells cultured in neutral (pH=7.2) and acidic (pH=5.5) medium. Furthermore, histamine treatment also significantly increased the transcriptional activity of NF-κB p65. High expression and transcriptional activity of NF-κB p65 significantly increased the mRNA expressions and concentrations of inflammatory cytokines, tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and interleukin 1 beta (IL-1β), thereby inducing the inflammatory response in bovine rumen epithelial cells. However, inhibition of NF-κB p65 by PDTC significantly decreased the expressions and concentrations of the inflammatory cytokines induced by histamine in the rumen epithelial cells cultured in the neutral and acidic medium. The present data indicate that histamine induces the inflammatory response of bovine rumen epithelial cells through the NF-κB pathway. © 2017 The Author(s). Published by S. Karger AG, Basel.

Comparative analysis of the in vitro cytotoxicity of the dietary biogenic amines tyramine and histamine.

Science.gov (United States)

Linares, Daniel M; del Rio, Beatriz; Redruello, Begoña; Ladero, Victor; Martin, M Cruz; Fernandez, Maria; Ruas-Madiedo, Patricia; Alvarez, Miguel A

2016-04-15

Tyramine and histamine, the most toxic biogenic amines (BA), are often found in high concentrations in certain foods. Prompted by the limited knowledge of BA toxicity, and increasing awareness of the risks associated with high intakes of dietary BA, the in vitro cytotoxicity of tyramine and histamine was investigated. Tyramine and histamine were toxic for HT29 intestinal cell cultures at concentrations commonly found in BA-rich food, as determined by real-time cell analysis. Surprisingly, tyramine had a stronger and more rapid cytotoxic effect than histamine. Their mode of action was also different, while tyramine caused cell necrosis, histamine induced apoptosis. To avoid health risks, the BA content of foods should be reduced and legal limits established for tyramine. Copyright © 2015 Elsevier Ltd. All rights reserved.

Inhibition of Ebola and Marburg Virus Entry by G Protein-Coupled Receptor Antagonists.

Science.gov (United States)

Cheng, Han; Lear-Rooney, Calli M; Johansen, Lisa; Varhegyi, Elizabeth; Chen, Zheng W; Olinger, Gene G; Rong, Lijun

2015-10-01

Filoviruses, consisting of Ebola virus (EBOV) and Marburg virus (MARV), are among the most lethal infectious threats to mankind. Infections by these viruses can cause severe hemorrhagic fevers in humans and nonhuman primates with high mortality rates. Since there is currently no vaccine or antiviral therapy approved for humans, there is an urgent need to develop prophylactic and therapeutic options for use during filoviral outbreaks and bioterrorist attacks. One of the ideal targets against filoviral infection and diseases is at the entry step, which is mediated by the filoviral glycoprotein (GP). In this report, we screened a chemical library of small molecules and identified numerous inhibitors, which are known G protein-coupled receptor (GPCR) antagonists targeting different GPCRs, including histamine receptors, 5-HT (serotonin) receptors, muscarinic acetylcholine receptor, and adrenergic receptor. These inhibitors can effectively block replication of both infectious EBOV and MARV, indicating a broad antiviral activity of the GPCR antagonists. The time-of-addition experiment and microscopic studies suggest that GPCR antagonists block filoviral entry at a step following the initial attachment but prior to viral/cell membrane fusion. These results strongly suggest that GPCRs play a critical role in filoviral entry and GPCR antagonists can be developed as an effective anti-EBOV/MARV therapy. Infection of Ebola virus and Marburg virus can cause severe illness in humans with a high mortality rate, and currently there is no FDA-approved vaccine or therapeutic treatment available. The 2013-2015 epidemic in West Africa underscores a lack of our understanding in the infection and pathogenesis of these viruses and the urgency of drug discovery and development. In this study, we have identified numerous inhibitors that are known G protein-coupled receptor (GPCR) antagonists targeting different GPCRs. These inhibitors can effectively block replication of both infectious

Comparison of analytical methods for the determination of histamine in reference canned fish samples

Science.gov (United States)

Jakšić, S.; Baloš, M. Ž.; Mihaljev, Ž.; Prodanov Radulović, J.; Nešić, K.

2017-09-01

Two screening methods for histamine in canned fish, an enzymatic test and a competitive direct enzyme-linked immunosorbent assay (CD-ELISA), were compared with the reversed-phase liquid chromatography (RP-HPLC) standard method. For enzymatic and CD-ELISA methods, determination was conducted according to producers’ manuals. For RP-HPLC, histamine was derivatized with dansyl-chloride, followed by RP-HPLC and diode array detection. Results of analysis of canned fish, supplied as reference samples for proficiency testing, showed good agreement when histamine was present at higher concentrations (above 100 mg kg-1). At a lower level (16.95 mg kg-1), the enzymatic test produced some higher results. Generally, analysis of four reference samples according to CD-ELISA and RP-HPLC showed good agreement for histamine determination (r=0.977 in concentration range 16.95-216 mg kg-1) The results show that the applied enzymatic test and CD-ELISA appeared to be suitable screening methods for the determination of histamine in canned fish.

The effect of nitric oxide synthase inhibition on histamine induced headache and arterial dilatation in migraineurs

DEFF Research Database (Denmark)

Lassen, L H; Christiansen, I; Iversen, Helle Klingenberg

2003-01-01

-decrease in MCA blood velocity, or dilatation of neither the temporal nor the radial artery. L-NMMA constricted the temporal artery by 8% before histamine infusion, whereas the radial artery was unaffected. The temporal artery dilated 4-5 times more than the radial artery during histamine infusion. In conclusion...... the use of a NOS inhibitor in the highest possible dose did not block the histamine-induced headache response or arterial dilatation. Either the concentration of L-NMMA reaching the smooth muscle cell was insufficient or, histamine dilates arteries and causes headache via NO independent mechanisms. Our...... results showed for the first time a craniospecificity for the vasodilating effect of histamine and for the arterial effects of NOS inhibition....

Different perception levels of histamine-induced itch sensation in young adult mice.

Science.gov (United States)

Ji, Yeounjung; Jang, Yongwoo; Lee, Wook Joo; Yang, Young Duk; Shim, Won-Sik

2018-05-01

Itch is an unpleasant sensation that evokes behavioral responses such as scratching the skin. Interestingly, it is conceived that the perception of itch sensation is influenced by age. Indeed, accumulating evidence supports the idea that even children or younger adults show distinctive itch sensation depending on age. This evidence implies the presence of a mechanism that regulates the perception of itch sensation in an age-dependent fashion. Therefore, the purpose of the present study was to investigate a putative mechanism for the age-dependent perception of itch sensation by comparing histamine-induced scratching behaviors in 45-day old (D45) and 75-day old male "young adult" mice. The results indicated that, following histamine administration, the D75 mice spent a longer time scratching than D45 mice. However, the intensity of the calcium influx induced by histamine in primary culture of dorsal root ganglia (DRG) neurons was not different between D45 and D75 mice. Moreover, no apparent difference was observed in mRNA levels of a characteristic His-related receptor and ion channel. In contrast, the mRNA levels of Toll-Like Receptor 4 (TLR4) were increased approximately by two-fold in D75 DRG compared with D45 DRG. Additionally, D75-derived DRG neurons exhibited enhanced intracellular calcium increase by lipopolysaccharide (LPS, a TLR4 agonist) than those of D45 mice. Furthermore, intensities of calcium influx induced by histamine were significantly potentiated when co-treated with LPS in D75 DRG neurons, but not in those of D45 mice. Thus, it appears that D75 mice showed enhanced histamine-induced scratching behaviors not by increased expression levels of histamine-related genes, but probably due to augmented TLR4 expression in DRG neurons. Consequently, the current study found that different perception levels of histamine-induced itch sensation are present in different age groups of young adult mice. Copyright © 2018 Elsevier Inc. All rights reserved.

Novel spirotetracyclic zwitterionic dual H(1)/5-HT(2A) receptor antagonists for the treatment of sleep disorders.

Science.gov (United States)

Gianotti, Massimo; Botta, Maurizio; Brough, Stephen; Carletti, Renzo; Castiglioni, Emiliano; Corti, Corrado; Dal-Cin, Michele; Delle Fratte, Sonia; Korajac, Denana; Lovric, Marija; Merlo, Giancarlo; Mesic, Milan; Pavone, Francesca; Piccoli, Laura; Rast, Slavko; Roscic, Maja; Sava, Anna; Smehil, Mario; Stasi, Luigi; Togninelli, Andrea; Wigglesworth, Mark J

2010-11-11

Histamine H(1) and serotonin 5-HT(2A) receptors mediate two different mechanisms involved in sleep regulation: H(1) antagonists are sleep inducers, while 5-HT(2A) antagonists are sleep maintainers. Starting from 9'a, a novel spirotetracyclic compound endowed with good H(1)/5-HT(2A) potency but poor selectivity, very high Cli, and a poor P450 profile, a specific optimization strategy was set up. In particular, we investigated the possibility of introducing appropriate amino acid moieties to optimize the developability profile of the series. Following this zwitterionic approach, we were able to identify several advanced leads (51, 65, and 73) with potent dual H(1)/5-HT(2A) activity and appropriate developability profiles. These compounds exhibited efficacy as hypnotic agents in a rat telemetric sleep model with minimal effective doses in the range 3-10 mg/kg po.

Biosensor cell assay for measuring real-time aldosterone-induced release of histamine from mesenteric arteries

DEFF Research Database (Denmark)

Dalgaard, Emil G; Andersen, Kenneth; Svenningsen, Per

2017-01-01

as a sensitive biosensor assay for histamine release from isolated mouse mesenteric arteries. Activation of the H1 receptor by histamine was measured as an increased number of intracellular Ca(2+) transient peaks using fluorescence imaging RESULTS: The developed biosensor was sensitive to histamine...... in physiological relevant concentrations and responded to substances released by the artery preparation. Aldosterone treatment of mesenteric arteries from wild type mice for 50 minutes resulted in an increased number of intracellular Ca(2+) transient peaks in the biosensor cells, which was significantly inhibited...... by the histamine H1 blocker pyrilamine. Mesenteric arteries from mast cell deficient SASH mice induced similar pyrilamine-sensitive Ca(2+) transient response in the biosensor cells. Mesenteric arteries from wild type and SASH mice expressed histamine decarboxylase mRNA, indicating that mast cells are not the only...

Amine dependence of proliferative activity in two transplantable lines of mouse colonic carcinoma.

Science.gov (United States)

Tutton, P J; Barkla, D H

1987-01-01

Serotonin, histamine and their antagonists have previously been shown to influence both the cell proliferation rate and the volumetric growth rate of colonic tumours. Of these earlier studies, those on cell proliferation could not distinguish between direct effects on tumour cells and indirect effects on the host, whereas those on the volumetric growth rate of tumours, whilst suggesting an outcome related to the individual properties of the tumour rather than the host, could not distinguish between influences on cell gain, cell loss or stromal changes. In an attempt to distinguish between these possibilities the current experiments on the mitotic rate in two lines of transplantable mouse colonic carcinoma were undertaken. One line of tumour proved to be sensitive to inhibition by a histamine H2 receptor antagonist and a dopamine D2 antagonist but resistant to serotonin antagonists; the inhibition by histamine antagonists was surmountable by co-administration of histamine. The other line proved to be highly sensitive to the inhibitory effects of serotonin antagonist and less so to antagonists of the other two amines and in this case the effect of serotonin antagonists was surmountable by serotonin. These results suggest that the variations between different colonic tumours in the response to amine antagonists is due to differences in the extent of inhibition of cell proliferation rather than differences in cell loss or stromal effects. Thus it appears likely that amine antagonists are able to directly interfere with the proliferation of some colonic tumour cells.

Mast cell-derived histamine mediates cystitis pain.

Directory of Open Access Journals (Sweden)

Charles N Rudick

2008-05-01

Full Text Available Mast cells trigger inflammation that is associated with local pain, but the mechanisms mediating pain are unclear. Interstitial cystitis (IC is a bladder disease that causes debilitating pelvic pain of unknown origin and without consistent inflammation, but IC symptoms correlate with elevated bladder lamina propria mast cell counts. We hypothesized that mast cells mediate pelvic pain directly and examined pain behavior using a murine model that recapitulates key aspects of IC.Infection of mice with pseudorabies virus (PRV induces a neurogenic cystitis associated with lamina propria mast cell accumulation dependent upon tumor necrosis factor alpha (TNF, TNF-mediated bladder barrier dysfunction, and pelvic pain behavior, but the molecular basis for pelvic pain is unknown. In this study, both PRV-induced pelvic pain and bladder pathophysiology were abrogated in mast cell-deficient mice but were restored by reconstitution with wild type bone marrow. Pelvic pain developed normally in TNF- and TNF receptor-deficient mice, while bladder pathophysiology was abrogated. Conversely, genetic or pharmacologic disruption of histamine receptor H1R or H2R attenuated pelvic pain without altering pathophysiology.These data demonstrate that mast cells promote cystitis pain and bladder pathophysiology through the separable actions of histamine and TNF, respectively. Therefore, pain is independent of pathology and inflammation, and histamine receptors represent direct therapeutic targets for pain in IC and other chronic pain conditions.

Influence of physical damage and freezing on histamine concentration and microbiological quality of yellowfin tuna during processing

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Gonzalo García-Tapia

2013-09-01

Full Text Available Yellowfin tuna has a high level of free histidine in their muscle, which can lead to histamine formation by microorganisms if temperature abuse occurs during handling and further processing. The objective of this study was to measure levels of histamine in damaged and undamaged thawed muscle to determine the effect of physical damage on the microbial count and histamine formation during the initial steps of canning processing and to isolate and identify the main histamine-forming microorganisms present in the flesh of yellowfin tuna. Total mesophilic and psicrophilic microorganisms were determined using the standard plate method. The presence of histamine-forming microorganisms was determined in a modified Niven's agar. Strains were further identified using the API 20E kit for enterobacteriaceae and Gram-negative bacilli. Physically damaged tuna did not show higher microbiological contamination than that of undamaged muscle tuna. The most active histamine-forming microorganism present in tuna flesh was Morganella morganii. Other decarboxylating microorganisms present were Enterobacter agglomerans and Enterobacter cloacae. Physical damage of tune during catching and handling did not increase the level of histamine or the amount of microorganisms present in tuna meat during frozen transportation, but they showed a higher risk of histamine-forming microorganism growth during processing.

Histamine is not released in acute thermal injury in human skin in vivo: a microdialysis study

DEFF Research Database (Denmark)

Petersen, Lars Jelstrup; Pedersen, Juri Lindy; Skov, Per Stahl

2009-01-01

BACKGROUND: Animal models have shown histamine to be released from the skin during the acute phase of a burn injury. The role of histamine during the early phase of thermal injuries in humans remains unclear. PURPOSE: The objectives of this trial were to study histamine release in human skin during...

Inhibitory effect of bacteriocin-producing lactic acid bacteria against histamine-forming bacteria isolated from Myeolchi-jeot

Directory of Open Access Journals (Sweden)

Eun-Seo Lim

2016-12-01

Full Text Available Abstract The objectives of this study were to identify the histamine-forming bacteria and bacteriocin- producing lactic acid bacteria (LAB isolated from Myeolchi-jeot according to sequence analysis of the 16S rRNA gene, to evaluate the inhibitory effects of the bacteriocin on the growth and histamine accumulation of histamine-forming bacteria, and to assess the physico-chemical properties of the bacteriocin. Based on 16S rRNA gene sequences, histamine-forming bacteria were identified as Bacillus licheniformis MCH01, Serratia marcescens MCH02, Staphylococcus xylosus MCH03, Aeromonas hydrophila MCH04, and Morganella morganii MCH05. The five LAB strains identified as Pediococcus acidilactici MCL11, Leuconostoc mesenteroides MCL12, Enterococcus faecium MCL13, Lactobacillus sakei MCL14, and Lactobacillus acidophilus MCL15 were found to produce an antibacterial compound with inhibitory activity against the tested histamine-producing bacteria. The inhibitory activity of these bacteriocins obtained from the five LAB remained stable after incubation at pH 4.0–8.0 and heating for 10 min at 80 °C; however, the bacteriocin activity was destroyed after treatment with papain, pepsin, proteinase K, α-chymotrypsin, or trypsin. Meanwhile, these bacteriocins produced by the tested LAB strains also exhibited histamine-degradation ability. Therefore, these antimicrobial substances may play a role in inhibiting histamine formation in the fermented fish products and preventing seafood-related food-borne disease caused by bacterially generated histamine.

Histamine poisoning from insect consumption: an outbreak investigation from Thailand.

Science.gov (United States)

Chomchai, Summon; Chomchai, Chulathida

2018-02-01

Insect consumption is a common practice in the Asian culture and all over the world. We are reporting an outbreak investigation of histamine poisoning from ingestion of fried insects. On 24 July 2014, a group of students at a seminar presented to Angthong Provincial Hospital, Thailand, with pruritic rash after ingesting snacks consisting of fried insects from a vendor. We initiated an outbreak investigation with retrospective cohort design and collected samples of remaining foods for analyses. Attack rates, relative risks and their confidence intervals (CI) were calculated. Out of 227 students, 28 developed illnesses that were consistent with our case definition which included, flushing, pruritus, urticarial rashes, headache, nausea, vomiting, diarrhea, dyspnea and bronchospasm. Two children were hospitalized for progressive bronchospasm overnight without serious complications. The types of food ingested included a lunch that was provided at the seminar for all students and snacks that 41 students bought from the only vendor in the vicinity. The snacks included fried grasshoppers, silkworm pupae, common green frogs, bamboo borers, crickets and meat balls. The attack rates were highest (82.6 and 85.0%) among students who ingested fried grasshoppers and silkworm pupae and lowest (4.4 and 5.3%) among those who did not ingest them, with relative risk of 18.7 (95% CI 9.6-36.4) for grasshoppers and 16.0 (95% CI 8.8-29.3) for silkworm pupae. Histamine concentrations in the fried grasshoppers and silkworm pupae were 9.73 and 7.66 mg/100g, respectively. Through epidemiological analysis and laboratory confirmation, we have illustrated that histamine poisoning can occur from ingestion of fried insects. We postulate that histidine, which is present in high concentration in grasshoppers and silkworm pupae, is decarboxylated by bacteria to histamine, a heat stable toxin. The ingestion of histamine is responsible for the clinical pictures being reported.

Potentiodynamic formation of gold nanoparticles film on glassy carbon electrode using aminophenyl diazonium cations grafted gold nanoparticles: Determination of histamine H2 receptor antagonist

International Nuclear Information System (INIS)

Kesavan, Srinivasan; Revin, S. Brillians; John, S. Abraham

2014-01-01

Graphical abstract: - Highlights: • Grafting based AuNPs were synthesized in aqueous medium by spontaneous grafting. • GC/ITO electrode was modified with AuNPs film by potentiodynamic method. • AuNPs film modified electrode was characterized by XPS, AFM and CV. • Simultaneous determination of ranitidine and paracetamol was demonstrated. • Practical application was demonstrated in commercial drugs. - Abstract: The aminophenyl (AP) functionalized AuNPs (AP-AuNPs) were synthesized in aqueous medium by spontaneous grafting method and were used for the formation of AuNPs film on glassy carbon (GC) and indium tin oxide (ITO) surfaces by potentiodynamic method. The formed AP-AuNPs film modified electrodes were characterized by cyclic voltammetry (CV), atomic force microscopy (AFM), electrochemical impedance spectroscopy (EIS), and X-ray photoelectron spectroscopy (XPS). EIS studies show that the electron transfer reaction of [Fe(CN) 6 ] 3-/4− was higher at the AP-AuNPs film modified electrode (1.58 × 10 −4 cm s −1 ) than at bare (3.78 × 10 −5 cm s −1 ) GC electrode. The surface coverage of the AP-AuNPs film modified electrode was found to be 4.4 × 10 −10 mol cm −2 . The film formation takes place via -NH 2 groups of AP-AuNPs, which was confirmed by XPS from the observed peaks corresponding to =N-H (396.7 eV), -N-H (399.2 eV), -N = N- (400.2 eV) and -N + -H (403.3 eV). The AP-AuNPs film modified electrode was successfully utilized for the determination of histamine H 2 receptor antagonist ranitidine (RA). Further, the AP-AuNPs film modified electrode was effectively used for the selective determination of RA in the presence of 40-fold excess paracetamol. The present method was successfully used to determine the concentration of RA in commercial drugs

Bronchial histamine challenge. A combined interrupter-dosimeter method compared with a standard method

DEFF Research Database (Denmark)

Pavlovic, M; Holstein-Rathlou, N H; Madsen, F

1985-01-01

We compared the provocative concentration (PC) values obtained by two different methods of performing bronchial histamine challenge. One test was done on an APTA, an apparatus which allows simultaneous provocation with histamine and measurement of airway resistance (Rtot) by the interrupter metho...

Sickle erythrocytes enhance phenylephrine and histamine

African Journals Online (AJOL)

Dr Olaleye

the influence of sickle erythrocyte on contractile responses induced by phenylephrine and histamine. ... obtained from subjects of different haemoglobin (Hb) genotypes (AA, AS and SS), under ... the sixth position of the β-chain of the hemoglobin S. Address for ... blood pressure values in sickle cell anaemia subjects as.

Preliminary study of histamine H4 receptor expressed on human CD4+ T cells and its immunomodulatory potency in the IL-17 pathway of psoriasis.

Science.gov (United States)

Han, Song Hee; Hur, Min Seok; Kim, Min Jung; Kim, Bo Mi; Kim, Kyoung Woon; Kim, Hae Rim; Choe, Yong Beom; Ahn, Kyu Joong; Lee, Yang Won

2017-10-01

Previous studies have shown the expression of histamine H 4 receptor (H4R) on CD4 + T cells, especially human CD4 + T h 2-polarized T cells. This study aimed to investigate the role of H4R on these effector T cells in psoriasis. We enrolled three patients each with active psoriasis, inactive psoriasis, scalp seborrheic dermatitis, and three normal controls, and compared the basal expression of H4R mRNA in their peripheral blood CD4 + T cells. Then, we identified H4R expression in dermal CD4 + T cells. Furthermore, we investigated H4R expression after stimulating separated peripheral blood CD4 + T cells with several inflammatory cytokines. The results showed higher H4R expression in the active psoriasis group compared to the inactive psoriasis group. It was interesting that interleukin (IL)-23, which is a representative cytokine contributing to T h 17 cell differentiation, stimulated H4R expression significantly. After adding a selective H4R antagonist (JNJ-7777120) while the CD4 + T cells were polarized into T h 17 cells, we observed a tendency toward suppressed IL-17 secretion. Histamine stimulation influences the IL-17 pathway in psoriasis via the fourth histamine receptor subtype, H4R, on CD4 + T cells. The immunomodulatory roles of H4R suggest its potency as a new therapeutic target for obstinate psoriasis. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Histamine delays gastric emptying of solid food in man through histamine, receptors

International Nuclear Information System (INIS)

Sridhar, K.; Lange, R.; McCallum, R.W.

1984-01-01

The authors have shown that histamine (H) contracts the cat pylorus and duodenum through H/sub 1/ receptor mechanisms. The authors investigated the effect of H infusion on gastric emptying (GE) and the role of H/sub 1/ and H/sub 2/ receptor blockade in healthy volunteers. Radionuclide GE studies were performed using chicken liver labeled in vivo with /sup 99m/Technetium-sulfur colloid as a marker of solid food. Study days were as follows: a baseline GE study (Day 1); H infused continuously IV at a rate of 40 μg/kg/hr during the GE study (Day 2); an IV bolus of 50 mg of diphenhydramine (Day 3), or 300 mg cimetidine (Day 4) given just prior to the continuous infusion of H; a final day when cimetidine was given alone (Day 5). GE was monitored for 2 hours on each day. The results of days 1, 2 and 3 are summarized below (+p<0.05 vs baseline or Day 1). Pretreatment with cimetidine (Day 4) augmented the delay in GE induced by H infusion, while cimetidine without H (Day 5) had no effect on GE. The authors conclude that: 1) H given at a dose which elicits maximal acid secretory response in man significantly delays GE; and 2) H/sub 1/ receptor blockade but not H/sub 2/ blockade prevented this effect. Histamine may play a modulatory role in human gastric emptying through an H/sub 1/ receptor mechanism

Cowhage-induced itch as an experimental model for pruritus. A comparative study with histamine-induced itch.

Directory of Open Access Journals (Sweden)

Alexandru D P Papoiu

2011-03-01

Full Text Available Histamine is the prototypical pruritogen used in experimental itch induction. However, in most chronic pruritic diseases, itch is not predominantly mediated by histamine. Cowhage-induced itch, on the other hand, seems more characteristic of itch occurring in chronic pruritic diseases.We tested the validity of cowhage as an itch-inducing agent by contrasting it with the classical itch inducer, histamine, in healthy subjects and atopic dermatitis (AD patients. We also investigated whether there was a cumulative effect when both agents were combined.Fifteen healthy individuals and fifteen AD patients were recruited. Experimental itch induction was performed in eczema-free areas on the volar aspects of the forearm, using different itch inducers: histamine, cowhage and their combination thereof. Itch intensity was assessed continuously for 5.5 minutes after stimulus application using a computer-assisted visual analogue scale (COVAS.In both healthy and AD subjects, the mean and peak intensity of itch were higher after the application of cowhage compared to histamine, and were higher after the combined application of cowhage and histamine, compared to histamine alone (p<0.0001 in all cases. Itch intensity ratings were not significantly different between healthy and AD subjects for the same itch inducer used; however AD subjects exhibited a prolonged itch response in comparison to healthy subjects (p<0.001.Cowhage induced a more intense itch sensation compared to histamine. Cowhage was the dominant factor in itch perception when both pathways were stimulated in the same time. Cowhage-induced itch is a suitable model for the study of itch in AD and other chronic pruritic diseases, and it can serve as a new model for testing antipruritic drugs in humans.

Increased release of histamine in patients with respiratory symptoms related to perfume

DEFF Research Database (Denmark)

Elberling, J; Skov, P S; Mosbech, H

2007-01-01

BACKGROUND: Environmental perfume exposure may cause respiratory symptoms. Individuals with asthma and perfume contact allergy report such symptoms more frequently than others. However, immunologic mechanisms have not been demonstrated and the symptoms are not associated with IgE-mediated allergy....... The study aimed to investigate whether basophils from patients with respiratory symptoms related to perfume released more histamine in the presence of perfume as compared with healthy volunteers. METHODS: Histamine release was measured by the glass fibre method. Blood was obtained from healthy volunteers (n......=20) and patients with respiratory symptoms related to perfume (n=17) attending a dermatological outpatient clinic for patch testing. The effect of an international brand perfume was investigated using the basophil histamine release test with perfume. Furthermore, basophils from a healthy non...

Sedation and memory: studies with a histamine H-1 receptor antagonist.

Science.gov (United States)

Turner, Claire; Handford, Alison D F; Nicholson, Anthony N

2006-07-01

The influence of sedation on the effect of an H-1 receptor antagonist on various cognitive functions, including memory, were evaluated. Diphenhydramine (50, 75 and 100 mg) and lorazepam (0.5 and 1.5 mg) were given on single occasions to 12 healthy volunteers (six males, six females) aged 20-33 (mean 23.4) years. Subjective assessments of sedation, sleep latencies, digit symbol substitution, choice reaction time, sustained attention and memory recall were studied 1.0 h before and 0.5, 2.0 and 3.5 h after drug ingestion. The study was double blind, placebo controlled and with a crossover design. With all doses of diphenhydramine there was subjective sedation, reduced sleep latencies and impairments in performance on the digit symbol substitution, choice reaction time and sustained attention tasks. No effects were observed with 0.5 mg lorazepam. With 1.5 mg lorazepam there was subjective sedation, fewer digit symbol substitutions, slowed choice reaction time, impaired attention and memory, but no effect on sleep latencies. Contrast analysis of data measured at all time points showed that although there was no difference in the effect of diphenhydramine (100 mg) and lorazepam (1.5 mg) on those tasks without a memory component, response times were slower with lorazepam on those tasks with a memory component. However, both 100 mg diphenhydramine and 1.5 mg lorazepam impaired prompted recall measured at 2 h post-ingestion only. It is considered that impaired memory is not necessarily associated with sedation, and that impairment of memory with drugs that lead to sedation may be effected through neuronal systems independent of those that affect arousal.

Synthesis of cationic diphosphine ruthenium complexes with nido-dicarbaundecaborate anions. Molecular structure of [RuCl(dppe)2]+[7,8-nido-C2B9H12]-

International Nuclear Information System (INIS)

Cheredilin, D.N.; Dolgushin, F.M.; Balagurova, E.V.; Godovikov, I.A.; Chizhevskij, I.T.

2004-01-01

Five new diphosphine ruthenium(II) complexes with nido-dicarbaundecaborate anions were synthesized. The composition and structure of the complexes were confirmed by data of 1 H, 31 P{ 1 H} NMR and elementary analysis. The crystal and molecular structure of solvated complex [RuCl(dppe) 2 + [7,8-nido-C 2 B 9 H 12 ] - ·CH 2 Cl 2 was ascertained by the method of X-ray diffraction analysis. It is shown that coordination sphere of ruthenium atom in the complex cation is a distorted trigonal bipyramid. The distances from ruthenium atom to phosphorus atoms are 2.398(1) and 2.391(1) A, while the angle P-Ru-P equals 175.85(5) Deg [ru

Induction of histamine release in vitro from rat peritoneal mast cells by extracts of grain dust.

Science.gov (United States)

Warren, C P; Holford-Strevens, V

1986-01-01

The ability of extracts of grain dust and wheat to induce histamine release from rat peritoneal cells was investigated. Some grain dusts, with a high endotoxin content, were found to produce cytotoxic histamine release. Extract of wheat dust, with a low endotoxin release, produced noncytotoxic histamine release from peritoneal cells but not from purified mast cells. This reaction was dependent on the presence of phosphatidyl serine. The agent did not appear to be a lectin because histamine release was not enhanced by passive sensitization of mast cells with IgE. The activity occurred only over a narrow range of concentrations of the extract of wheat. The cause was unclear. PMID:2423321

The effect of vacuum packaging on histamine changes of milkfish sticks at various storage temperatures.

Science.gov (United States)

Kung, Hsien-Feng; Lee, Yi-Chen; Lin, Chiang-Wei; Huang, Yu-Ru; Cheng, Chao-An; Lin, Chia-Min; Tsai, Yung-Hsiang

2017-10-01

The effects of polyethylene packaging (PEP) (in air) and vacuum packaging (VP) on the histamine related quality of milkfish sticks stored at different temperatures (-20°C, 4°C, 15°C, and 25°C) were studied. The results showed that the aerobic plate count (APC), pH, total volatile basic nitrogen (TVBN), and histamine contents increased as storage time increased when the PEP and VP samples were stored at 25°C. At below 15°C, the APC, TVBN, pH, and histamine levels in PEP and VP samples were retarded, but the VP samples had considerably lower levels of APC, TVBN, and histamine than PEP samples. Once the frozen fish samples stored at -20°C for 2 months were thawed and stored at 25°C, VP retarded the increase of histamine in milkfish sticks as compared to PEP. In summary, this result suggested the milkfish sticks packed with VP and stored below 4°C could prevent deterioration of product quality and extend shelf-life. Copyright © 2017. Published by Elsevier B.V.

Generation of a proton motive force by histidine decarboxylation and electrogenic histidine/histamine antiport in Lactobacillus buchneri.

Science.gov (United States)

Molenaar, D; Bosscher, J S; ten Brink, B; Driessen, A J; Konings, W N

1993-05-01

Lactobacillus buchneri ST2A vigorously decarboxylates histidine to the biogenic amine histamine, which is excreted into the medium. Cells grown in the presence of histidine generate both a transmembrane pH gradient, inside alkaline, and an electrical potential (delta psi), inside negative, upon addition of histidine. Studies of the mechanism of histidine uptake and histamine excretion in membrane vesicles and proteoliposomes devoid of cytosolic histidine decarboxylase activity demonstrate that histidine uptake, histamine efflux, and histidine/histamine exchange are electrogenic processes. Histidine/histamine exchange is much faster than the unidirectional fluxes of these substrates, is inhibited by an inside-negative delta psi and is stimulated by an inside positive delta psi. These data suggest that the generation of metabolic energy from histidine decarboxylation results from an electrogenic histidine/histamine exchange and indirect proton extrusion due to the combined action of the decarboxylase and carrier-mediated exchange. The abundance of amino acid decarboxylation reactions among bacteria suggests that this mechanism of metabolic energy generation and/or pH regulation is widespread.

Studies on the role of central histamine in the acquisition of a radiation-induced conditioned taste aversion

International Nuclear Information System (INIS)

Rabin, B.M.; Hunt, W.A.; Lee, J.

1982-01-01

The experiments described in this report were designed to test two hypotheses about how exposure to low-level radiation can affect the behavior of an organism: first, tht radiation effects on behavior are mediated by a radiation-induced release of histamine; and second, that this radiation-induced histamine release can exert relatively direct effects on the central nervous system. The results of the first experiment showed that microinjection of histamine directly into the fourth ventricle of rats produced a taste aversion to a novel sucrose solution. Pretreating rats with intraventricular H 1 or H 2 blockers was not effective in preventing the acquisition of the radiation-induced aversion, although the H 1 blocker did prevent the acquisition of a histamine-induced taste aversion. It also was not possible to establish a cross-tolerance between centrally administered histamine and radiation. The results are interpreted as not supporting the hypothesis that a radiation-induced release of central histamine mediates the acquisition of a conditioned taste aversion following exposure to low-level radiation

Validation of basophil histamine release against the autologous serum skin test and outcome of serum-induced basophil histamine release studies in a large population of chronic urticaria patients

DEFF Research Database (Denmark)

Platzer, M H; Grattan, C E H; Poulsen, Lars K.

2005-01-01

the immunoglobulin E (IgE) or the high affinity IgE receptor (FcepsilonRI) and serum-induced histamine release (HR) from basophils and mast cells. We have examined the correlation between the ASST and a new basophil histamine-releasing assay (the HR-Urtikaria test) in a group of well-characterized CU patients...... and subsequently determined the frequency of HR-Urticaria-positive sera from a larger population of CU patients....

Generation of a homology model of the human histamine H3 receptor for ligand docking and pharmacophore-based screening

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Schlegel, Birgit; Laggner, Christian; Meier, Rene; Langer, Thierry; Schnell, David; Seifert, Roland; Stark, Holger; Höltje, Hans-Dieter; Sippl, Wolfgang

2007-08-01

The human histamine H3 receptor (hH3R) is a G-protein coupled receptor (GPCR), which modulates the release of various neurotransmitters in the central and peripheral nervous system and therefore is a potential target in the therapy of numerous diseases. Although ligands addressing this receptor are already known, the discovery of alternative lead structures represents an important goal in drug design. The goal of this work was to study the hH3R and its antagonists by means of molecular modelling tools. For this purpose, a strategy was pursued in which a homology model of the hH3R based on the crystal structure of bovine rhodopsin was generated and refined by molecular dynamics simulations in a dipalmitoylphosphatidylcholine (DPPC)/water membrane mimic before the resulting binding pocket was used for high-throughput docking using the program GOLD. Alternatively, a pharmacophore-based procedure was carried out where the alleged bioactive conformations of three different potent hH3R antagonists were used as templates for the generation of pharmacophore models. A pharmacophore-based screening was then carried out using the program Catalyst. Based upon a database of 418 validated hH3R antagonists both strategies could be validated in respect of their performance. Seven hits obtained during this screening procedure were commercially purchased, and experimentally tested in a [3H]Nα-methylhistamine binding assay. The compounds tested showed affinities at hH3R with K i values ranging from 0.079 to 6.3 μM.

Histamine intolerance as a cause of chronic digestive complaints in pediatric patients

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Antonio Rosell-Camps

2013-04-01

Full Text Available Introduction: histamine intolerance (HI is a poorly described disease in gastroenterology that may present with predominant digestive complaints. The goals of this study include a report of two cases diagnosed in a pediatric gastroenterology clinic. Material and methods: observational, retrospective study of patients diagnosed with HI from September 2010 to December 2011 at the pediatric gastroenterology clinic of a tertiary hospital. They were deemed to have a diagnosis of HI in the presence of 2 or more characteristic digestive complaints, decreased diamino oxidase (DAO levels and/or response to a low histamine diet with negative IgE-mediated food allergy tests. Results: sixteen patients were diagnosed. Males predominated versus females (11/5. Mean age at symptom onset was 4 years (6 months vs. 13 years and 6 months and mean age at diagnosis was 6 years and 6 months (17 months vs. 13 years and 11 months, with an interval of 2 years and 1 month between symptom onset and diagnosis (5 months vs. 4 years. Predominant symptoms included diffuse abdominal pain (16/16, intermittent diarrhea (10/16, headache (5/16, intermittent vomiting (4/16, and skin rash (2/16. The diagnosis was established by measuring plasma diamino oxidase levels, which were below 10 kU/L (normal > 10 kU/L in 14 cases, and symptom clearance on initiating a low histamine diet. In two patients DAO levels were above 10 kU/L but responded to diet. Treatment was based on a diet low in histamine-contaning food, and antihistamines H1 y H2 had to be added for two cases. Conclusions: histamine intolerance is a little known disease with a potentially relevant incidence. Predominant complaints include diffuse abdominal pain, diarrhea, headache, and chronic intermittent vomiting. Its diagnosis is based on clinical suspicion, plasma DAO measurement, and response to a low histamine diet. Management with the latter provides immediate improvement.

Precooking as a Control for Histamine Formation during the Processing of Tuna: An Industrial Process Validation.

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Adams, Farzana; Nolte, Fred; Colton, James; De Beer, John; Weddig, Lisa

2018-02-23

An experiment to validate the precooking of tuna as a control for histamine formation was carried out at a commercial tuna factory in Fiji. Albacore tuna ( Thunnus alalunga) were brought on board long-line catcher vessels alive, immediately chilled but never frozen, and delivered to an on-shore facility within 3 to 13 days. These fish were then allowed to spoil at 25 to 30°C for 21 to 25 h to induce high levels of histamine (>50 ppm), as a simulation of "worst-case" postharvest conditions, and subsequently frozen. These spoiled fish later were thawed normally and then precooked at a commercial tuna processing facility to a target maximum core temperature of 60°C. These tuna were then held at ambient temperatures of 19 to 37°C for up to 30 h, and samples were collected every 6 h for histamine analysis. After precooking, no further histamine formation was observed for 12 to 18 h, indicating that a conservative minimum core temperature of 60°C pauses subsequent histamine formation for 12 to 18 h. Using the maximum core temperature of 60°C provided a challenge study to validate a recommended minimum core temperature of 60°C, and 12 to 18 h was sufficient to convert precooked tuna into frozen loins or canned tuna. This industrial-scale process validation study provides support at a high confidence level for the preventive histamine control associated with precooking. This study was conducted with tuna deliberately allowed to spoil to induce high concentrations of histamine and histamine-forming capacity and to fail standard organoleptic evaluations, and the critical limits for precooking were validated. Thus, these limits can be used in a hazard analysis critical control point plan in which precooking is identified as a critical control point.

ANTISECRETORY TREATMENT FOR PEDIATRIC GASTROESOPHAGEAL REFLUX DISEASE - A SYSTEMATIC REVIEW.

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Mattos, Ângelo Zambam de; Marchese, Gabriela Meirelles; Fonseca, Bárbara Brum; Kupski, Carlos; Machado, Marta Brenner

2017-12-01

Proton pump inhibitors and histamine H2 receptor antagonists are two of the most commonly prescribed drug classes for pediatric gastroesophageal reflux disease, but their efficacy is controversial. Many patients are treated with these drugs for atypical manifestations attributed to gastroesophageal reflux, even that causal relation is not proven. To evaluate the use of proton pump inhibitors and histamine H2 receptor antagonists in pediatric gastroesophageal reflux disease through a systematic review. A systematic review was performed, using MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials databases. The search was limited to studies published in English, Portuguese or Spanish. There was no limitation regarding date of publication. Studies were considered eligible if they were randomized-controlled trials, evaluating proton pump inhibitors and/or histamine H2 receptor antagonists for the treatment of pediatric gastroesophageal reflux disease. Studies published only as abstracts, studies evaluating only non-clinical outcomes and studies exclusively comparing different doses of the same drug were excluded. Data extraction was performed by independent investigators. The study protocol was registered at PROSPERO platform (CRD42016040156). After analyzing 735 retrieved references, 23 studies (1598 randomized patients) were included in the systematic review. Eight studies demonstrated that both proton pump inhibitors and histamine H2 receptor antagonists were effective against typical manifestations of gastroesophageal reflux disease, and that there was no evidence of benefit in combining the latter to the former or in routinely prescribing long-term maintenance treatments. Three studies evaluated the effect of treatments on children with asthma, and neither proton pump inhibitors nor histamine H2 receptor antagonists proved to be significantly better than placebo. One study compared different combinations of omeprazole, bethanechol and placebo for the

A comparison of in vivo and in vitro human airway reactivity to histamine.

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Armour, C L; Lazar, N M; Schellenberg, R R; Taylor, S M; Chan, N; Hogg, J C; Paré, P D

1984-06-01

To examine for a relationship between in vivo nonspecific bronchial reactivity to histamine and in vitro smooth muscle response to histamine, we performed inhalation dose-response curves prior to lung surgery in 12 patients and compared this with their bronchial smooth muscle response in vitro. In vivo reactivity was assessed by the provocative concentration of histamine resulting in a 20% fall in forced expiratory volume in one second (PC20), and in vitro reactivity was measured by the negative log of the molar concentration of histamine producing 50% maximal contraction (pD2) as well as maximal tension generated (Tmax). In addition, morphometric analysis was performed on the in vitro tissue to quantitate the amount of smooth muscle present. A wide range of in vivo responses was found in the 12 subjects (PC20-0.065 lead to 16). There was less in vitro variability and no correlation between PC20 and in vitro reactivity assessed by pD20 or Tmax or between PC20 and the percent of smooth muscle.

Desipramine inhibits histamine H1 receptor-induced Ca2+ signaling in rat hypothalamic cells.

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Ji-Ah Kang

Full Text Available The hypothalamus in the brain is the main center for appetite control and integrates signals from adipose tissue and the gastrointestinal tract. Antidepressants are known to modulate the activities of hypothalamic neurons and affect food intake, but the cellular and molecular mechanisms by which antidepressants modulate hypothalamic function remain unclear. Here we have investigated how hypothalamic neurons respond to treatment with antidepressants, including desipramine and sibutramine. In primary cultured rat hypothalamic cells, desipramine markedly suppressed the elevation of intracellular Ca(2+ evoked by histamine H1 receptor activation. Desipramine also inhibited the histamine-induced Ca(2+ increase and the expression of corticotrophin-releasing hormone in hypothalamic GT1-1 cells. The effect of desipramine was not affected by pretreatment with prazosin or propranolol, excluding catecholamine reuptake activity of desipramine as an underlying mechanism. Sibutramine which is also an antidepressant but decreases food intake, had little effect on the histamine-induced Ca(2+ increase or AMP-activated protein kinase activity. Our results reveal that desipramine and sibutramine have different effects on histamine H1 receptor signaling in hypothalamic cells and suggest that distinct regulation of hypothalamic histamine signaling might underlie the differential regulation of food intake between antidepressants.

Endophytic Fungi Associated With Turmeric (Curcuma longa L. Can Inhibit Histamine-Forming Bacteria in Fish

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Eris Septiana

2017-01-01

Full Text Available Turmeric (Curcuma longa L. is a medicinal plant that is commonly used as spice and preservative. Many types of endophytic fungi have been reported as being associated with medicinal plants and able to synthesize secondary metabolites. In this study, endophytic fungi were isolated from all plant parts of turmeric plants. Identification of the endophytic fungi was done using morphological characteristics and sequencing of the internal transcribed spacer (ITS region of ribosomal DNA. The dual culture method was used for screening antibacterial activity of the endophytic fungi against Morganella morganii, a common histamine-producing bacteria. The disc diffusion method was used to test the ability of water fractions of selected endophytic fungi to inhibit M. morganii growth. Two-dimensional thin layer chromatography was used to determine the fungal extract inhibition activity on histamine formation. In total, 11 endophytic fungi were successfully isolated and identified as Arthrobotrys foliicola, Cochliobolus kusanoi, Daldinia eschscholzii, Fusarium oxysporum, Fusarium proliferatum, Fusarium solani, Fusarium verticillioides, Phanerochaete chrysosporium, and Phaeosphaeria ammophilae. Five isolates showed inhibition activity against M. morganii in the dual culture tests. Based on the disc diffusion assay, A. foliicola and F. verticillioides inhibited the growth of M. morganii as a histamine-producing bacteria, and inhibiting histamine formation in fish. The best effects in inhibiting growth of the histamine-producing bacteria and histamine formation inhibition in fish were produced with F. verticillioides water fraction at 0°C incubation.

Aspirin Augments IgE-Mediated Histamine Release from Human Peripheral Basophils via Syk Kinase Activation

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Hiroaki Matsuo

2013-01-01

Conclusions: Aspirin enhanced histamine release from basophils via increased Syk kinase activation, and that the augmentation of histamine release by NSAIDs or FAs may be one possible cause of worsening symptoms in patients with chronic urticaria and FDEIA.

Validation of histamine determination Method in yoghurt using High Performance Liquid Chromatography

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M Jahedinia

2014-02-01

Full Text Available Biogenic amines are organic, basic nitrogenous compounds of low molecular weight that are mainly generated by the enzymatic decarboxylation of amino acids by microorganisms. Dairy products are among the foods with the highest amine content. A wide variety of methods and procedures for determination of histamine and biogenic amines have been established. Amongst, HPLC method is considered as reference method. The aim of this study was to validate Reversed Phase HPLC method determination of histamine in yoghurt. The mobile phase consisted of acetonitrile/water (18:88 v/v and the flow rate was set at 0.5 ml/min using isocratic HPLC. Detection was carried out at 254 nm using UV-detector. Calibration curve that was constructed using peak area of standards was linear and value of correlation coefficient (r2 was estimated at 0.998. Good recoveries were observed for histamine under investigation at all spiking levels and average of recoveries was 84%. The RSD% value from repeatability test was found to be %4.4. Limit of detection and limit of quantitation were 0.14 and 0.42 µ/ml, respectively. The results of validation tests showed that the method is reliable and rapid for quantification of histamine in yoghurt.

Histamine 1 Receptor Blockade Enhances Eosinophil-Mediated Clearance of Adult Filarial Worms.

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Ellen Mueller Fox

Full Text Available Filariae are tissue-invasive nematodes that cause diseases such as elephantiasis and river blindness. The goal of this study was to characterize the role of histamine during Litomosoides sigmodontis infection of BALB/c mice, a murine model of filariasis. Time course studies demonstrated that while expression of histidine decarboxylase mRNA increases throughout 12 weeks of infection, serum levels of histamine exhibit two peaks-one 30 minutes after primary infection and one 8 weeks later. Interestingly, mice treated with fexofenadine, a histamine receptor 1 inhibitor, demonstrated significantly reduced worm burden in infected mice compared to untreated infected controls. Although fexofenadine-treated mice had decreased antigen-specific IgE levels as well as lower splenocyte IL-5 and IFNγ production, they exhibited a greater than fourfold rise in eosinophil numbers at the tissue site where adult L. sigmodontis worms reside. Fexofenadine-mediated clearance of L. sigmodontis worms was dependent on host eosinophils, as fexofenadine did not decrease worm burdens in eosinophil-deficient dblGATA mice. These findings suggest that histamine release induced by tissue invasive helminths may aid parasite survival by diminishing eosinophilic responses. Further, these results raise the possibility that combining H1 receptor inhibitors with current anthelmintics may improve treatment efficacy for filariae and other tissue-invasive helminths.

Can human allergy drug fexofenadine, an antagonist of histamine (H1) receptor, be used to treat dog and cat? Homology modeling, docking and molecular dynamic Simulation of three H1 receptors in complex with fexofenadine.

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Sader, Safaa; Cai, Jun; Muller, Anna C G; Wu, Chun

2017-08-01

Fexofenadine, a potent antagonist to human histamine 1 (H 1 ) receptor, is a non-sedative third generation antihistamine that is widely used to treat various human allergic conditions such as allergic rhinitis, conjunctivitis and atopic dermatitis. Encouragingly, it's been successfully used to treat canine atopic dermatitis, this supports the notion that it might have a great potential for treating other canine allergic conditions and other mammal pets such as dog. Regrettably, while there is a myriad of studies conducted on the interactions of antihistamines with human H 1 receptor, the similar studies on non-human pet H 1 are considerably scarce. The published studies using the first and second generation antihistamines drugs have shown that the antihistamine response is varied and unpredictable. Thus, to probe its efficacy on pet, the homology models of dog and cat H 1 receptors were built based on the crystal structure of human H 1 receptor bound to antagonist doxepin (PDB 3RZE) and fexofenadine was subsequently docked to human, dog and cat H 1 receptors. The docked complexes are then subjected to 1000ns molecular dynamics (MD) simulations with explicit membrane. Our calculated MM/GBSA binding energies indicated that fexofenadine binds comparably to the three receptors; and our MD data also showed the binding poses, structural and dynamic features among three receptors are very similar. Therefore, our data supported the application of fexofenadine to the H 1 related allergic conditions of dog and cat. Nonetheless, subtle systemic differences among human, dog and cat H 1 receptors were also identified. Clearly, there is still a space to develop a more selective, potent and safe antihistamine alternatives such as Fexofenadine for dog or cat based on these differences. Our computation approach might provide a fast and economic way to predict if human antihistamine drugs can also be safely and efficaciously administered to animals. Copyright © 2017 Elsevier Inc

Histamine H4 receptor in oral lichen planus.

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Salem, A; Al-Samadi, A; Stegajev, V; Stark, H; Häyrinen-Immonen, R; Ainola, M; Hietanen, J; Konttinen, Y T

2015-04-01

Oral lichen planus (OLP) is an autoimmune disease characterized by a band-like T-cell infiltrate below the apoptotic epithelial cells and degenerated basement membrane. We tested the hypothesis that the high-affinity histamine H4 receptors (H4 Rs) are downregulated in OLP by high histamine concentrations and proinflammatory T-cell cytokines. Immunohistochemistry and immunofluorescence staining, image analysis and quantitative real-time polymerase chain reaction of tissue samples and cytokine-stimulated cultured SCC-25 and primary human oral keratinocytes. H4 R immunoreactivity was weak in OLP and characterized by mast cell (MC) hyperplasia and degranulation. In contrast to controls, H4 R immunostaining and MC counts were negatively correlated in OLP (P = 0.003). H4 R agonist at nanomolar levels led to a rapid internalization of H4 Rs, whereas high histamine concentration and interferon-γ decreased HRH4 -gene transcripts. Healthy oral epithelial cells are equipped with H4 R, which displays a uniform staining pattern in a MC-independent fashion. In contrast, in OLP, increased numbers of activated MCs associate with increasing loss of epithelial H4 R. Cell culture experiments suggest a rapid H4 R stimulation-dependent receptor internalization and a slow cytokine-driven decrease in H4 R synthesis. H4 R may be involved in the maintenance of healthy oral mucosa. In OLP, this maintenance might be impaired by MC degranulation and inflammatory cytokines. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A mixture of anatase and rutile TiO2 nanoparticles induces histamine secretion in mast cells

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Chen Eric Y

2012-01-01

Full Text Available Abstract Background Histamine released from mast cells, through complex interactions involving the binding of IgE to FcεRI receptors and the subsequent intracellular Ca2+ signaling, can mediate many allergic/inflammatory responses. The possibility of titanium dioxide nanoparticles (TiO2 NPs, a nanomaterial pervasively used in nanotechnology and pharmaceutical industries, to directly induce histamine secretion without prior allergen sensitization has remained uncertain. Results TiO2 NP exposure increased both histamine secretion and cytosolic Ca2+ concentration ([Ca2+]C in a dose dependent manner in rat RBL-2H3 mast cells. The increase in intracellular Ca2+ levels resulted primarily from an extracellular Ca2+ influx via membrane L-type Ca2+ channels. Unspecific Ca2+ entry via TiO2 NP-instigated membrane disruption was demonstrated with the intracellular leakage of a fluorescent calcein dye. Oxidative stress induced by TiO2 NPs also contributed to cytosolic Ca2+ signaling. The PLC-IP3-IP3 receptor pathways and endoplasmic reticulum (ER were responsible for the sustained elevation of [Ca2+]C and histamine secretion. Conclusion Our data suggests that systemic circulation of NPs may prompt histamine release at different locales causing abnormal inflammatory diseases. This study provides a novel mechanistic link between environmental TiO2 NP exposure and allergen-independent histamine release that can exacerbate manifestations of multiple allergic responses.

Effect of histamine-2-receptor antagonists versus sucralfate on stress ulcer prophylaxis in mechanically ventilated patients: a meta-analysis of 10 randomized controlled trials.

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Huang, Jiahao; Cao, Yunfei; Liao, Cun; Wu, Liucheng; Gao, Feng

2010-01-01

We conducted a meta-analysis in order to investigate the effect of histamine-2-receptor antagonists (H2RA) versus sucralfate on stress ulcer prophylaxis in mechanically ventilated patients in the intensive care unit (ICU). A systematic literature search of Medline, EMBASE, Cochrane Central Register of Controlled Trials (1966 to January 2010) was conducted using specific search terms. A review of Web of Science and a manual review of references were also performed. Eligible studies were randomized control trials (RCTs) that compared H2RA and sucralfate for the prevention of stress ulcer in mechanically ventilated patients. Main outcome measures were rates of overt bleeding, clinically important gastrointestinal (GI) bleeding, ventilator-associated pneumonia, gastric colonization and ICU mortality. Ten RCTs with 2,092 participants on mechanical ventilation were identified. Meta-analysis showed there was a trend toward decreased overt bleeding when H2RA was compared with sucralfate (OR = 0.87, 95% CI: 0.49 to 1.53). A total of 12 clinically important GI bleeding events occurred among 667 patients (1.8%) in the H2RA group compared with 26 events among 673 patients (3.9%) in the sucralfate groups. Prophylaxis with sucralfate decreased the incidence of gastric colonization (OR = 2.03, 95% CI: 1.29 to 3.19) and ventilator-associated pneumonia (OR = 1.32, 95% CI: 1.07 to 1.64). Subgroup analysis showed H2RA was not superior to sucralfate in reducing early-onset pneumonia (OR = 0.62, 95%CI: 0.36 to 1.07) but had a higher late-onset pneumonia rate (OR = 4.36, 95%CI: 2.09 to 9.09) relative to sucralfate. No statistically significant reduction was observed in mortality of ICU between groups (OR = 1.08, 95% CI: 0.86 to 1.34). In patients with mechanical ventilation, H2RA resulted in no differential effectiveness in treating overt bleeding, but had higher rates of gastric colonization and ventilator-associated pneumonia. Additional RCTs of stress ulcer prophylaxis with H2RA and

New trends in combined use of gonadotropin-releasing hormone antagonists with gonadotropins or pulsatile gonadotropin-releasing hormone in ovulation induction and assisted reproductive technologies.

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Gordon, K; Danforth, D R; Williams, R F; Hodgen, G D

1992-10-01

The use of gonadotropin-releasing hormone agonists as adjunctive therapy with gonadotropins for ovulation induction in in vitro fertilization and other assisted reproductive technologies has become common clinical practice. With the recent advent of potent gonadotropin-releasing hormone antagonists free from the marked histamine-release effects that stymied earlier compounds, an attractive alternative method may be available. We have established the feasibility of combining gonadotropin-releasing hormone antagonist-induced inhibition of endogenous gonadotropins with exogenous gonadotropin therapy for ovulation induction in a nonhuman primate model. Here, the principal benefits to be gained from using the gonadotropin-releasing hormone antagonist rather than the gonadotropin-releasing hormone agonist are the immediate inhibition of pituitary gonadotropin secretion without the "flare effect," which brings greater safety and convenience for patients and the medical team and saves time and money. We have also recently demonstrated the feasibility of combining gonadotropin-releasing hormone antagonist with pulsatile gonadotropin-releasing hormone therapy for the controlled restoration of gonadotropin secretion and gonadal steroidogenesis culminating in apparently normal (singleton) ovulatory cycles. This is feasible only with gonadotropin-releasing hormone antagonists because, unlike gonadotropin-releasing hormone agonists, they achieve control of the pituitary-ovarian axis without down regulation of the gonadotropin-releasing hormone receptor system. This capacity to override gonadotropin-releasing hormone antagonist-induced suppression of pituitary-ovarian function may allow new treatment modalities to be employed for women who suffer from chronic hyperandrogenemia with polycystic ovarian disease.

Mastocytosis and adverse reactions to biogenic amines and histamine-releasing foods : what is the evidence?

NARCIS (Netherlands)

Viieg-Boerstra, BJ; van der Heide, S; Elberink, JNGO; Kluin-Nelemans, JC; Dubois, AEJ

2005-01-01

Background: It has been suggested that normal concentrations of biogenic amines and 'histamine-releasing foods' may exacerbate symptoms in mastocytosis. The purpose of this study was to look for scientific evidence in the literature on diets restricted in biogenic amines and histamine-releasing

Histamine development and bacterial diversity in microbially-challenged tonggol (Thunnus tonggol) under temperature abuse during canning manufacture.

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Hongpattarakere, Tipparat; Buntin, Nirunya; Nuylert, Aem

2016-01-01

Histamine formation and bacteriological changes caused by temperature abuse commonly occurring in the manufacturing process of standard canned tuna was assessed in microbiologically challenged tonggol (Thunnus tonggol). The in situ challenge was performed by water-soaking at 26-28 °C for 7 h to ensure the multiplication and active phase of fish microflora. Right after pre-cooking to back-bone temperature (BBT) of 50-52 °C, histamine dropped to 5.17 ± 2.71 ppm, and slowly reached 6.84 ± 1.69 ppm at 16 h abuse. On the contrary, histamine was reduced to 2.87 ± 1.23 ppm and eventually reached 5.01 ± 1.32 ppm at 24 h abuse in the pre-cooked fish previously frozen. The numbers of total aerobic bacteria, Enterobactericeae, psychrotroph, histamine forming bacteria (HFB) and diversity of fish microflora were revealed by cultural and nested PCR-Denaturing Gradient Gel Electrophoresis (PCR-DGGE) techniques. Interestingly, frozen storage effectively halted histamine formation in raw fish throughout 16 h abuse despite the presence of HFB. These included the prolific strains of Morganella morganii, Proteus penneri, Proteus mirabilin, Citrobacter spp. The nested PCR-DGGE profile confirmed the presence of M. morganii and Citrobacter spp. in raw fish. These prolific strains were hardly observed in the precooked fish previously frozen. Frozen storage did not only promote even histamine distribution throughout fish muscle but also enhanced histamine loss during thawing and pre-cooking. Therefore, pre-cooking and frozen storage were proven to be the effective combined hurdles not only to reduce but also prolong histamine formation of the challenged toggol throughout 24 h of temperature abuse during canning process.

Effect of methylmercury on histamine release from rat mast cells

Energy Technology Data Exchange (ETDEWEB)

Graevskaya, Elizabeth E.; Rubin, Andrew B. [Moscow State University, Biological Faculty, Department of Biophysics, 119899, Vorobjovy Gory, Moscow (Russian Federation); Yasutake, Akira; Aramaki, Ryoji [National Institute for Minamata Disease, 4058-18 Hama, Minamata, Kumamoto 867-0008 (Japan)

2003-01-01

Methylmercury chloride (MeHgCl) is well known as a significant environmental hazard, particularly as a modulator of the immune system. As it is acknowledged that the critical effector cells in the host response participating in various biological responses are mast cells, we tried to define the possible contribution of mast cells in the development of methylmercury-evoked effects. We investigated the effects of methylmercury on the rat mast cell degranulation induced by non-immunological stimuli (the selective liberator of histamine, compound 48/80, and calcium ionophore A23187) both in vivo and in vitro. Using the cells prepared from methylmercury-intoxicated rats through a 5-day treatment of MeHgCl (10 mg/kg/day), we observed the suppression of calcium ionophore A23187- and 48/80-induced histamine release, which was enhanced with time after treatment. Similar suppression was observed in the ionophore-stimulated release, when cells were prepared from rat with a single treatment of MeHgCl (20 mg/kg). It should be noted that when cells from the control rat were pre-incubated with methylmercury in vitro at a 10{sup -8} M concentration for 10 min, A23187 and compound 48/80-stimulated histamine release was significantly enhanced. However, when the pre-incubation period was prolonged to 30 min, the release was suppressed. An increase in the methylmercury concentration to 10{sup -6} M also suppressed the histamine release. These results show that methylmercury treatment can modify mast cell function depending on concentration and time, and might provide an insight into the role of mast cells in the development of methylmercury-stimulated effects. (orig.)

A glial variant of the vesicular monoamine transporter is required to store histamine in the Drosophila visual system.

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Rafael Romero-Calderón

2008-11-01

Full Text Available Unlike other monoamine neurotransmitters, the mechanism by which the brain's histamine content is regulated remains unclear. In mammals, vesicular monoamine transporters (VMATs are expressed exclusively in neurons and mediate the storage of histamine and other monoamines. We have studied the visual system of Drosophila melanogaster in which histamine is the primary neurotransmitter released from photoreceptor cells. We report here that a novel mRNA splice variant of Drosophila VMAT (DVMAT-B is expressed not in neurons but rather in a small subset of glia in the lamina of the fly's optic lobe. Histamine contents are reduced by mutation of dVMAT, but can be partially restored by specifically expressing DVMAT-B in glia. Our results suggest a novel role for a monoamine transporter in glia that may be relevant to histamine homeostasis in other systems.

Autonomous control of phosphatidylinositol turnover by histamine and acetylcholine receptors in the NIE-115 neuron-like cell line

International Nuclear Information System (INIS)

Large, T.H.; Lambert, M.P.; Cohen, N.M.; Klein, W.L.

1986-01-01

Histamine was found to stimulate the turnover of phosphatidylinositol (PI) in cultures of neuron-like NE-115 cells. Turnover was measured by increased production of ( 3 H)inositol phosphates (breakdown) and by accelerated incorporation of 32 P into PI (resynthesis). Data were consistent with hydrolysis of polyphosphoinositides being the initial event in receptor-stimulated PI turnover. This response to histamine desensitized within 10 min. Receptor systems for histamine and acetylcholine were tested for possible interactions: PI turnover in response to dual stimulation was approximately equal to the sum of the individual responses while prior desensitization of the acetylcholine receptor system had no effect on subsequent stimulation of the histamine receptor system. These results are consistent with the hypothesis that components of acetylcholine and histamine receptor systems responsible for PI turnover are autonomously organised and regulated. (author)

Conditioning pain stimulation does not affect itch induced by intra-epidermal histamine pricks but aggravates neurogenic inflammation in healthy volunteers

DEFF Research Database (Denmark)

Andersen, Hjalte Holm; Imai, Yosuke; Petersen, Kristian Kjær

2016-01-01

This study investigated whether itch induced by intra-epidermal histamine is subjected to modulation by a standardized conditioned pain modulation (CPM) paradigm in 24 healthy volunteers. CPM was induced by computer-controlled cuff pressure algometry and histamine was introduced to the volar...... forearm by skin prick test punctures. Moreover, neurogenic inflammation and wheal reactions induced by histamine and autonomic nervous system responses (heart rate variability and skin conductance) were monitored. CPM did not modulate the intensity of histamine-induced itch suggesting that pruriceptive...... signaling is not inhibited by pain-recruited endogenous modulation, however, CPM was found to aggravate histamine-induced neurogenic inflammation, likely facilitated by efferent sympathetic fibers....

Diamine Oxidase from White Pea (Lathyrus sativus) Combined with Catalase Protects the Human Intestinal Caco-2 Cell Line from Histamine Damage.

Science.gov (United States)

Jumarie, Catherine; Séïde, Marilyne; Marcocci, Lucia; Pietrangeli, Paola; Mateescu, Mircea Alexandru

2017-07-01

Diamine oxidase (DAO) administration has been proposed to treat certain gastrointestinal dysfunctions induced by histamine, an immunomodulator, signaling, and pro-inflammatory factor. However, H 2 O 2 resulting from the oxidative deamination of histamine by DAO may be toxic. The purpose of this study was to investigate to which extent DAO from white pea (Lathyrus sativus), alone or in combination with catalase, may modulate histamine toxicity in the human intestinal Caco-2 cell line. The results show that histamine at concentrations higher than 1 mM is toxic to the Caco-2 cells, independently of the cell differentiation status, with a LC 50 of ≅ 10 mM following a 24-h exposure. Depending on its concentration, DAO increased histamine toxicity to a greater extent in differentiated cells compared to undifferentiated cultures. In the presence of catalase, the DAO-induced increase in histamine toxicity was completely abolished in the undifferentiated cells and only partially decreased in differentiated cells, showing differences in the sensitivity of Caco-2 cells to the products resulting from histamine degradation by DAO (H 2 O 2 , NH 3 , or imidazole aldehyde). It appears that treatment of food histaminosis using a combination of vegetal DAO and catalase would protect against histamine toxicity and prevent H 2 O 2 -induced damage that may occur during histamine oxidative deamination.

[Outbreak due to butterfish consumption: keriorrhea and histamine poisoning].

Science.gov (United States)

Fariñas Cabrero, Maria Azucena; Berbel Hernández, Clara; Allué Tango, Marta; Díez Hillera, Margarita; Herrero Marcos, Juan Antonio

2015-01-01

The consumption of butterfish is spreading in our country; if appropriate standards of conservation and preparation of this type of food are not met may cause poisoning. The objective is to describe an outbreak of histamine poisoning and double cerous esters after consumption butterfish. A descriptive study of the double intoxication at a banquet held in July 2013 in Valladolid. It was studied by filling a specific survey, by phone or by the medical centers who treated the guests. The database and subsequent descriptive statistical analyzes were performed with Microsoft Excel Professional Plus 2010 program. Of the 27 cases reported in 24 we obtained information on symptoms. The attack rate was 22.5 %, with a clinical picture in which predominant diarrhea (75%), headache (46%), abdominal pain (38%) and sweating (38%), highlighting its specificity itching/burning of mouth (29%). Four patients had orange and oily stools (keriorrhea). The average time from the start of dinner to onset of symptoms was 119 minutes. The mean duration of symptoms was 14 hours. Analytical served fish showed histamine levels above 2,000 mg / kg. A double poisoning (histamine and cerous esters) was produced by consumption of butterfish. The picture was mild and self-limiting. You need to know this type of poison to properly handle avoiding unnecessary tests, and to notify the health authority for investigation and subsequent adoption of appropriate measures.

Skin reactions to histamine of healthy subjects after hypnotically induced emotions of sadness, anger, and happiness.

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Zachariae, R; Jørgensen, M M; Egekvist, H; Bjerring, P

2001-08-01

The severity of symptoms in asthma and other hypersensitivity-related disorders has been associated with changes in mood but little is known about the mechanisms possibly mediating such a relationship. The purpose of this study was to examine the influence of mood on skin reactivity to histamine by comparing the effects of hypnotically induced emotions on flare and wheal reactions to cutaneous histamine prick tests. Fifteen highly hypnotically susceptible volunteers had their cutaneous reactivity to histamine measured before hypnosis at 1, 2, 3, 4, 5, 10, and 15 min after the histamine prick. These measurements were repeated under three hypnotically induced emotions of sadness, anger, and happiness presented in a counterbalanced order. Skin reactions were measured as change in histamine flare and wheal area in mm2 per minute. The increase in flare reaction in the time interval from 1 to 3 min during happiness and anger was significantly smaller than flare reactions during sadness (P<0.05). No effect of emotion was found for wheal reactions. Hypnotic susceptibility scores were associated with increased flare reactions at baseline (r=0.56; P<0.05) and during the condition of happiness (r=0.56; P<0.05). Our results agree with previous studies showing mood to be a predictor of cutaneous immediate-type hypersensitivity and histamine skin reactions. The results are also in concordance with earlier findings of an association between hypnotic susceptibility and increased reactivity to an allergen.

Development and validation of a spectrophotometry method for the determination of histamine in fresh tuna (Thunnus tunna)

International Nuclear Information System (INIS)

Chacon-Silva, Fainier; Barquero-Quiros, Miriam

2002-01-01

Histamine in foods can promote allergic reactions in sensitive persons. A colorimetric microscale method for histamine determination was developed and validated. Cu 2+ histamine chelation occurs at 9,5 ph. Dichloromethane extraction of the complex as the salt with tetrabromo phenolphthalein ethyl ester, allows photometric quantitation at 515 nm. The validation of micro method was accomplished trough its performance parameters, detection limit, quantitation limit, sensitivity, linearity, precision, recuperation. This methodology was applied to twenty raw tuna samples, collected in San Jose metropolitan area. It was found that 45% of analyzed samples had a histamine content in the range between 100-200 mg/kg. This finding indicates bacterial contamination, 15% of samples analyzed were over 500 mg/kg FDA level of sanitary risk. (Author) [es

Histamine production by Raoultella ornithinolytica in mahi-mahi meat at various storage temperatures

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Chung-Saint Lin

2016-04-01

Full Text Available Mahi-mahi meat was inoculated with Raoultella ornithinolytica at 5.0 log CFU/g and stored at −20°C, 4°C, 15°C, 25°C, or 37°C to investigate bacterial growth and formation of total volatile base nitrogen and histamine in mahi-mahi meat. R. ornithinolytica grew rapidly in samples stored at temperature above 15°C. The histamine contents quickly increased to higher than 50 mg/100 g in samples stored at 25°C and 37°C within 12 hours as well as those stored at 15°C within 48 hours. The total volatile base nitrogen contents increased to higher than the index level (30 mg/100 g for fish decomposition at 25°C within 48 hours and 37°C within 24 hours. However, bacterial growth and histamine formation were controlled by cold storage of the samples at 4°C or below. Once the frozen mahi-mahi samples stored at −20°C for 2 months were thawed and stored at 25°C after 24 hours, histamine started to accumulate rapidly (>50 mg/100 g of fish.

Effects of lead and mercury on histamine uptake by glial and endothelial cells

Energy Technology Data Exchange (ETDEWEB)

Huszti, Z. [Semmelweis Univ. of Medicine, Dept. of Pharmacodynamics, Budapest (Hungary); Balogh, I. [Semmelweis Univ. of Medicine, Forensic Medicine, Budapest (Hungary)

1995-06-01

The effects of lead and mercury on [{sup 3}H]-histamine uptake by cultured astroglial and endothelial cells of rat brain were studied. Experimental data showed that both metal ions inhibited the uptake in both cell types of concentrations as low as 1-10 {mu}M. The effects were consistent with non/competitive inhibitions. With either lead or mercury exposure, the inhibition of the uptake was greater in astroglial than in cerebral endothelial cells. Contrary to the above finding, 100 {mu}M of mercuric chloride produced stimulation of histamine uptake and this stimulation was much more pronounced in cultured cerebral endothelial cells than in astroglial cells. Inhibition of [{sup 3}H]-histamine uptake by lead acetate and mercuric chloride was considered to be association with a loss of the transmembrane Na{sup +} and/or K{sup +} gradient while stimulation of the uptake by high concentration of mercury might be related to a direct effect on histamine transporter. It is note-worthy, that cultured astroglial cells, derived from neonatal rat brain, are much more sensitive to the toxic effects of these heavy metal ions than cultured endothelial cells derived from the brain capillaries often same species of animals. (au) 18 refs.

The histamine H₃ receptor as a therapeutic drug target for metabolic disorders: status, challenges and opportunities.

Science.gov (United States)

Plancher, Jean-Marc

2011-01-01

Since the histamine-3 receptor (H₃R) was cloned in 1999, huge efforts have been made by most of the key players in the pharmaceutical industry as well as in smaller biotech companies to increase the knowledge on this peculiar receptor, with the ultimate goal of bringing new drugs to the market. This review gives a survey on the most valuable chemical tools discovered so far and the significant pharmacological experiments on metabolic disease models published to date. Pharmacology of H₃R antagonists turns out to be very complex due to various functional activities, species selectivity, presence of H₃R isoforms and the poorly understood dichotomy in efficacy between CNS and metabolic disease models. Adding an extra layer of complexity, researchers have to cope with some recurrent safety concerns, some of them being tightly linked to the nature of the H₃R pharmacophore. Therefore this review also strives to summarize the major hurdles and some of the contradictions seen in the H₃R field, together with a brief overview of the clinical trials currently running.

En route to new blockbuster antihistamines:surveying the offspring of the expanding histamine receptor family

NARCIS (Netherlands)

Leurs, R.; Vischer, H.F.; Wijtmans, M.; De Esch, I.J.

2011-01-01

With the recognition of two new histamine receptors at the start of the new millennium, the field of histamine research has seen a clear revival. In the last 10 years, many academic and industrial groups have taken up the challenge to target these new members of the aminergic G-protein-coupled

Enhanced Indirect Photochemical Transformation of Histidine and Histamine through Association with Chromophoric Dissolved Organic Matter.

Science.gov (United States)

Chu, Chiheng; Lundeen, Rachel A; Remucal, Christina K; Sander, Michael; McNeill, Kristopher

2015-05-05

Photochemical transformations greatly affect the stability and fate of amino acids (AAs) in sunlit aquatic ecosystems. Whereas the direct phototransformation of dissolved AAs is well investigated, their indirect photolysis in the presence of chromophoric dissolved organic matter (CDOM) is poorly understood. In aquatic systems, CDOM may act both as sorbent for AAs and as photosensitizer, creating microenvironments with high concentrations of photochemically produced reactive intermediates, such as singlet oxygen (1O2). This study provides a systematic investigation of the indirect photochemical transformation of histidine (His) and histamine by 1O2 in solutions containing CDOM as a function of solution pH. Both His and histamine showed pH-dependent enhanced phototransformation in the CDOM systems as compared to systems in which model, low-molecular-weight 1O2 sensitizers were used. Enhanced reactivity resulted from sorption of His and histamine to CDOM and thus exposure to elevated 1O2 concentrations in the CDOM microenvironment. The extent of reactivity enhancement depended on solution pH via its effects on the protonation state of His, histamine, and CDOM. Sorption-enhanced reactivity was independently supported by depressed rate enhancements in the presence of a cosorbate that competitively displaced His and histamine from CDOM. Incorporating sorption and photochemical transformation processes into a reaction rate prediction model improved the description of the abiotic photochemical transformation rates of His in the presence of CDOM.

Detection and Characterization of Histamine-Producing Strains of Photobacterium damselae subsp. damselae Isolated from Mullets

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Marcello Trevisani

2017-06-01

Full Text Available Photobacterium damselae subsp. damselae (Pdd is considered to be an emerging pathogen of marine fish and has also been implicated in cases of histamine food poisoning. In this study, eight strains isolated from mullets of the genera Mugil and Liza captured in the Ligurian Sea were characterized, and a method to detect histamine-producing Pdd from fish samples was developed. The histamine-producing potential of the strains was evaluated in culture media (TSB+ using a histamine biosensor. Subsequently, two strains were used to contaminate mackerel fillets (4 or 40 CFU/g, simulating a cross-contamination on the selling fish stalls. Sample homogenates were enriched in TSB+. The cultures were then inoculated on thiosulfate-citrate-bile salts-sucrose agar (TCBS and the dark green colonies were cultured on Niven agar. The violet isolates were characterized using specific biochemical and PCR based tests. All Pdd strains were histamine producers, yielding concentration varying from 167 and 8977 µg/mL in TSB+ cultures incubated at 30 °C for 24 h. Pdd colonies were detected from the inoculated mackerel samples and their histidine decarboxylase gene was amplified using species-specific primer pairs designed for this study. The results indicate that mullets can be source of Pdd and the fish retailers needs to evaluate the risk posed by cross-contamination on the selling fish stalls.

Cultured smooth muscle cells of the human vesical sphincter are more sensitive to histamine than are detrusor smooth muscle cells.

Science.gov (United States)

Neuhaus, Jochen; Oberbach, Andreas; Schwalenberg, Thilo; Stolzenburg, Jens-Uwe

2006-05-01

To compare histamine receptor expression in cultured smooth muscle cells from the human detrusor and internal sphincter using receptor-specific agonists. Smooth muscle cells from the bladder dome and internal sphincter were cultured from 5 male patients undergoing cystectomy for bladder cancer therapy. Calcium transients in cells stimulated with carbachol, histamine, histamine receptor 1 (H1R)-specific heptanecarboxamide (HTMT), dimaprit (H2R), and R-(alpha)-methylhistamine (H3R) were measured by calcium imaging. Histamine receptor proteins were detected by Western blot analysis and immunocytochemistry. H1R, H2R, and H3R expression was found in tissue and cultured cells. Carbachol stimulated equal numbers of detrusor and sphincter cells (60% and 51%, respectively). Histamine stimulated significantly more cells than carbachol in detrusor (100%) and sphincter (99.34%) cells. Calcium responses to carbachol in detrusor and sphincter cells were comparable and did not differ from those to histamine in detrusor cells. However, histamine and specific agonists stimulated more sphincter cells than did carbachol (P <0.001), and the calcium increase was greater in sphincter cells than in detrusor cells. Single cell analysis revealed comparable H2R responses in detrusor and sphincter cells, but H1R and H3R-mediated calcium reactions were significantly greater in sphincter cells. Histamine very effectively induces calcium release in smooth muscle cells. In sphincter cells, histamine is even more effective than carbachol regarding the number of reacting cells and the intracellular calcium increase. Some of the variability in the outcome of antihistaminic interstitial cystitis therapies might be caused by the ineffectiveness of the chosen antihistaminic or unintentional weakening of sphincteric function.

Histamine influences body temperature by acting at H1 and H3 receptors on distinct populations of preoptic neurons.

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Lundius, Ebba Gregorsson; Sanchez-Alavez, Manuel; Ghochani, Yasmin; Klaus, Joseph; Tabarean, Iustin V

2010-03-24

The preoptic area/anterior hypothalamus, a region that contains neurons that control thermoregulation, is the main locus at which histamine affects body temperature. Here we report that histamine reduced the spontaneous firing rate of GABAergic preoptic neurons by activating H3 subtype histamine receptors. This effect involved a decrease in the level of phosphorylation of the extracellular signal-regulated kinase and was not dependent on synaptic activity. Furthermore, a population of non-GABAergic neurons was depolarized, and their firing rate was enhanced by histamine acting at H1 subtype receptors. In our experiments, activation of the H1R receptors was linked to the PLC pathway and Ca(2+) release from intracellular stores. This depolarization persisted in TTX or when fast synaptic potentials were blocked, indicating that it represents a postsynaptic effect. Single-cell reverse transcription-PCR analysis revealed expression of H3 receptors in a population of GABAergic neurons, while H1 receptors were expressed in non-GABAergic cells. Histamine applied in the median preoptic nucleus induced a robust, long-lasting hyperthermia effect that was mimicked by either H1 or H3 histamine receptor subtype-specific agonists. Our data indicate that histamine modulates the core body temperature by acting at two distinct populations of preoptic neurons that express H1 and H3 receptor subtypes, respectively.

Non-celiac gluten sensitivity: people without celiac disease avoiding gluten-is it due to histamine intolerance?

Science.gov (United States)

Schnedl, Wolfgang J; Lackner, Sonja; Enko, Dietmar; Schenk, Michael; Mangge, Harald; Holasek, Sandra J

2018-04-01

Food intolerance/malabsorption is caused by food ingredients, carbohydrates (mainly lactose and fructose), proteins (gluten), and biogenic amines (histamine) which cause nonspecific gastrointestinal and extra-intestinal symptoms. Here we focus on possible etiologic factors of intolerance/malabsorption especially in people with non-celiac gluten sensitivity (NCGS) or the so-called people without celiac disease avoiding gluten (PWCDAG) and histamine intolerance. Recognizing the recently described symptoms of NCGS (PWCDAG) we review correlations and parallels to histamine intolerance (HIT). We show that intestinal and extra-intestinal NCGS (PWCDAG) symptoms are very similar to those which can be found in histamine intolerance. After a detailed diagnostic workup for all possible etiologic factors in every patient, a targeted dietary intervention for single or possibly combined intolerance/malabsorption might be more effective than a short-term diet low in fermentable oligo-, di- and monosaccharides and polyols (FODMAP) or the untargeted uncritical use of gluten-free diets.

Paracetamol (acetaminophen) attenuates in vitro mast cell and peripheral blood mononucleocyte cell histamine release induced by N-acetylcysteine.

Science.gov (United States)

Coulson, James; Thompson, John Paul

2010-02-01

The treatment of acute paracetamol (acetaminophen) poisoning with N-acetylcysteine (NAC) is frequently complicated by an anaphylactoid reaction to the antidote. The mechanism that underlies this reaction is unclear. We used the human mast cell line 1 (HMC-1) and human peripheral blood mononucleocytes (PBMCs) to investigate the effects of NAC and paracetamol on histamine secretion in vitro. HMC-1 and human PBMCs were incubated in the presence of increasing concentrations of NAC +/- paracetamol. Cell viability was determined by the Trypan Blue Assay, and histamine secretion was measured by ELISA. NAC was toxic to HMC-1 cells at 100 mg/mL and to PBMCs at 67 mg/mL. NAC increased HMC-1 and PBMC histamine secretion at concentrations of NAC from 20 to 50 mg/mL and 2.5 to 100 mg/mL, respectively. NAC-induced histamine secretion by both cell types was reduced by co-incubation with 2.5 mg/mL of paracetamol. Paracetamol (acetaminophen) is capable of modifying histamine secretion in vitro. This may explain the clinical observation of a lower incidence of adverse reactions to NAC in vivo when higher concentrations of paracetamol are present than when paracetamol concentrations are low. Paracetamol (acetaminophen) attenuates in vitro mast cell and PBMC cell histamine release induced by NAC.

Histamine release inhibitory activity of Piper nigrum leaf.

Science.gov (United States)

Hirata, Noriko; Naruto, Shunsuke; Inaba, Kazunori; Itoh, Kimihisa; Tokunaga, Masashi; Iinuma, Munekazu; Matsuda, Hideaki

2008-10-01

Oral administration of a methanolic extract of Piper nigrum leaf (PN-ext, 50, 200 and 500 mg/kg) showed a potent dose-dependent inhibition of dinitrofluorobenzene (DNFB)-induced cutaneous reaction at 1 h [immediate phase response (IPR)] after and 24 h [late phase response (LPR)] after DNFB challenge in mice which were passively sensitized with anti-dinitrophenyl (DNP) IgE antibody. Ear swelling inhibitory effect of PN-ext (50, 200 and 500 mg/kg, per os (p.o.)) on very late phase response (vLPR) in the model mice was significant but weaker than that on IPR. Oral administration of PN-ext (50, 200 and 500 mg/kg for 7 d) inhibited picryl chloride (PC)-induced ear swelling in PC sensitized mice. PN-ext exhibited in vitro inhibitory effect on compound 48/80-induced histamine release from rat peritoneal mast cells. Two lignans of PN-ext, (-)-cubebin (1) and (-)-3,4-dimethoxy-3,4-desmethylenedioxycubebin (2), were identified as major active principles having histamine release inhibitory activity.

Role of histamine in the inhibitory effects of phycocyanin in experimental models of allergic inflammatory response

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D. Remirez

2002-01-01

Full Text Available It has recently been reported that phycocyanin, a biliprotein found in the blue-green microalgae Spirulina, exerts anti-inflammatory effects in some animal models of inflammation. Taking into account these findings, we decided to elucidate whether phycocyanin might exert also inhibitory effects in the induced allergic inflammatory response and on histamine release from isolated rat mast cells. In in vivo experiments, phycocyanin (100, 200 and 300 mg/kg post-orally (p.o. was administered 1 h before the challenge with 1 μg of ovalbumin (OA in the ear of mice previously sensitized with OA. One hour later, myeloperoxidase activity and ear edema were assessed. Phycocyanin significantly reduced both parameters. In separate experiments, phycocyanin (100 and 200 mg/kg p.o. also reduced the blue spot area induced by intradermal injections of histamine, and the histamine releaser compound 48/80 in rat skin. In concordance with the former results, phyco-cyanin also significantly reduced histamine release induced by compound 48/80 from isolated peritoneal rat mast cells. The inhibitory effects of phycocyanin were dose dependent. Taken together, our results suggest that inhibition of allergic inflammatory response by phycocyanin is mediated, at least in part, by inhibition of histamine release from mast cells.

Evaluation and identification of histamine-forming bacteria on fish products of middle Adriatic Sea

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Rocco Mancusi

2013-04-01

Full Text Available Regulation EU 2073/2005 sets maximum concentration for histamine in fish and products thereof. To meet these criteria, manufacturers have to define performance objectives, such as the maximum allowed prevalence and number/activity of histamine-producing bacteria at relevant stage of production. In order to assess the presence and decarboxylase activity of contaminant bacteria we examined 51 samples of blue fish caught and processed in Emilia Romagna region. We collected 50 gr of fish (skin and gills or the entire product from 10 sample units from every lot. Analytical samples were cultured in Trypticase Soy Broth supplemented with histidine and pyridoxal HCl. Histamine was measured with an electrochemical biosensor after incubation at both 37°C for 24 h and 18-22°C for 48 h. Enrichments that showed relevant enzymatic activity were seeded on Niven agar to isolate suspected colonies and DNA extracts from these bacteria were analyzed by polymerase chain reaction (PCR for detecting specific sequences of the gene encoding pyridoxaldependent histidine decarboxylase (HDC. Overall, 29.4% samples showed relevant production of histamine in broth cultures (above a cut-off value set at 250 ng/mL and 53.3% of them (8 out of 15 samples allowed detection of HDC positive strains. All of them were typed as Morganella, which appears to be the most common of fish caught in middle Adriatic sea. Ten out of the twelve positive samples with enrichment cultures incubated at both 37 and 18-22°C (83% showed higher decarboxylase activity at room temperature, suggesting the presence of psychrotolerant strains. In addition, the prevalence of histamine-producing bacteria was higher at retail than at production level, probably as a consequence of manipulations and cross-contamination. The risk correlated to development of histamine-producing psychrotolerans bacteria cannot be controlled only with storage temperature: it is necessary for the food business operators to

Histamine H3 receptor activation selectively inhibits dopamine D1 receptor-dependent [3H]GABA release from depolarization-stimulated slices of rat substantia nigra pars reticulata

International Nuclear Information System (INIS)

Aceves, J.; Young, J.M.; Arias-Montano, J.A.; Floran, B.; Garcia, M.

1997-01-01

The release of [ 3 H]GABA from slices of rat substantia nigra pars reticulata induced by increasing extracellular K + from 6 to 15 mM in the presence of 10 μM sulpiride was inhibited by 73±3% by 1 μM SCH 23390, consistent with a large component of release dependent upon D 1 receptor activation. The histamine H 3 receptor-selective agonist immepip (1 μM) and the non-selective agonist histamine (100 μM) inhibited [ 3 H]GABA release by 78±2 and 80±2%, respectively. The inhibition by both agonists was reversed by the H 3 receptor antagonist thioperamide (1 μM). However, in the presence of 1 μM SCH 23390 depolarization-induced release of [ 3 H]GABA was not significantly decreased by 1 μM immepip. In rats depleted of dopamine by pretreatment with reserpine, immepip no longer inhibited control release of [ 3 H]GABA, but in the presence of 1 μM SKF 38393, which produced a 7±1-fold stimulation of release, immepip reduced the release to a level not statistically different from that in the presence of immepip alone. Immepip (1 μM) also inhibited the depolarization-induced release of [ 3 H]dopamine from substantia nigra pars reticulata slices, by 38±3%.The evidence is consistent with the proposition that activation of histamine H 3 receptors leads to the selective inhibition of the component of depolarization-induced [ 3 H]GABA release in substantia nigra pars reticulata slices which is dependent upon D 1 receptor activation. This appears to be largely an action at the terminals of the striatonigral GABA projection neurons, which may be enhanced by a partial inhibition of dendritic [ 3 H]dopamine release. (Copyright (c) 1997 Elsevier Science B.V., Amsterdam. All rights reserved.)

Growth and histamine formation of Morganella morganii in determining the safety and quality of inoculated and uninoculated bluefish (Pomatomus saltatrix).

Science.gov (United States)

Lorca, T A; Gingerich, T M; Pierson, M D; Flick, G J; Hackney, C R; Sumner, S S

2001-12-01

The objective of this study was to determine the effect of normal microflora and Morganella morganii on histamine formation and olfactory acceptability in raw bluefish under controlled storage conditions. Fillets inoculated with and without M. morganii were stored at 5, 10, and 15 degrees C for 7 days. Microbial isolates from surface swabs were identified and screened for histidine decarboxylase activity. Olfactory acceptance was performed by an informal sensory panel. Histamine levels were quantified using high-performance liquid chromatography and fluorescence detection. While olfactory acceptance decreased, histamine concentration and bacterial counts increased. Storage temperature had a significant effect on histamine levels, bacterial counts, and olfactory acceptance of the bluefish. Inoculation with M. morganii had a positive significant effect on histamine formation for bluefish held at 10 and 15 degrees C (P bluefish.

Development of an analytical method for the determination of histamine in fish by liquid chromatography of high performance in reverse phase

International Nuclear Information System (INIS)

Valverde Chavarria, Juan Carlos; Barquero Quiros, Mirian

2004-01-01

The histamine is a biogenic amine able to promote allergic intoxications in sensitive persons. For this reason is necessary to have a method of analysis with sensitivity, precision and accuracy able to quantify lower amounts than actual FDA Normative sets. A reverse phase chromatographic method was developed. To identify and quantify histamine through automatic generation of histamine derivative of OPA, using an ultraviolet detector, performance parameters of developed method were adequate to quantification of histamine amount lower than FDA Normative. (Author) [es

Canine postradiation histamine levels and subsequent response to Compound 48/80

International Nuclear Information System (INIS)

Cockerham, L.G.; Doyle, T.F.; Donlon, M.A.; Helgeson, E.A.

1984-01-01

Radiation-induced hypotension in the beagle is accompanied by increased intestinal blood flow (IBF) and hematocrit (HCT). This study was performed to correlate these radiation-induced changes with plasma histamine (PH) levels following radiation. The histamine (H) levels were monitored in the systemic arterial circulation (SA) and the hepatic portal vein (HPV) before and after radiation. To examine the effect of radiation on the mobilization of total body H stores, Compound 48/80 was given I.V., and H responses were monitored in both control and radiated animals. Data obtained indicated that 100 Gy, whole-body, gamma-radiation produced a decrease in systemic mean blood pressure (BP), an increase in IBF and an increase in HCT. Concurrently, the mean PH/SA values increased and the PH/HPV levels decreased. Compound 48/80 produced a marked increase in PH levels in both control and radiated animals however, the levels found in the radiated animals were consistently lower than those in the controls, although not statistically different. This implies that H may mediate these observed intestinal responses and that the mobility of histamine is decreased in radiated animals. 19 references

Utilization of adenosine triphosphate in rat mast cells during histamine release induced by the ionophore A23187

DEFF Research Database (Denmark)

Johansen, Torben

1979-01-01

The role of endogenous adenosine triphosphate (ATP) in histamine release from rat mast cells induced by the ionophore A23187 in vitro has been studied. 2 The amount of histamine released by calcium from rat mast cells primed with the ionophore A23187 was dependent on the ATP content of the mast...... cells. 3 In aerobic experiments a drastic reduction in mast cell ATP content was found during the time when histamine release induced by A23187 takes place. 4 Anaerobic experiments were performed with metabolic inhibitors (antimycin A, oligomycin, and carbonyl cyanide p......-trifluorometroxyphenylnydrazone), which are known to block the energy-dependent calcium uptake by isolated mitochondria. The mast cell ATP content was reduced during A23187-induced histamine release under anaerobic conditions in the presence of glucose. This indicates an increased utilization of ATP during the release process. 5...

The Effects of Histaminergic Agents in the Nucleus ccumbens of Rats in the Elevated Plus-Maze Test of Anxiety

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Ameneh Rezayof

2010-05-01

Full Text Available "n Objective: "n The nucleus accumbens (NAc receive histaminergic neurons from tuberomammillary nuclei. There are reports indicating that central histamine systems are involved in many physiological behavioral processes, including anxiety. The aim of the present study was to assess whether the histaminergic system of the NAc is involved in anxiety-related behaviors. Methods: Rats were anesthetized with intra-peritoneal injection of ketamine hydrochloride, plus xylazine and then were placed in a stereotaxic apparatus. In addition, two stainless-steel cannuale were placed 2 mm above the nucleus accumbens shell. Seven days after recovery from surgery, the behavioral testing was started. As a model of anxiety, the elevated plus maze which is a useful test to investigate the effects of anxiogenic or anxiolytic drugs in rodents, was used in male Wistar rats.  "nResults: Intra-NAc administration of histamine (0.01, 0.1 and 1 µg/rat increased the percentage of open arm time (%OAT and open arm entries (%OAE ,but not locomotor activity, indicating an anxiolytic response. Furthermore, bilateral  microinjections of different doses of the H1 receptor  antagonist pyrilamine (0.001, 0.01, 0.1 and 1 µg/rat or the H2 receptor antagonist ranitidine (0.001, 0.01, 0.1 and 1 µg/rat into the NAc increased %OAT and %OAE , but not locomotor activity. However, both histamine and histamine receptor antagonists showed an anxiolytic-like effect ; the antagonists (1 µg/rat also decreased the histamine response. "n "n Conclusion: The results may indicate a modulatory effect for the H1 and H2 histamine receptors of nucleus accumbens in the anxiety behavior of rats.

The Itch-Producing Agents Histamine and Cowhage Activate Separate Populations of Primate Spinothalamic Tract Neurons

Science.gov (United States)

Davidson, Steve; Zhang, Xijing; Yoon, Chul H.; Khasabov, Sergey G.; Simone, Donald A.; Giesler, Glenn J.

2010-01-01

Itch is an everyday sensation, but when associated with disease or infection it can be chronic and debilitating. Several forms of itch can be blocked using antihistamines, but others cannot and these constitute an important clinical problem. Little information is available on the mechanisms underlying itch that is produced by nonhistaminergic mechanisms. We examined the responses of spinothalamic tract neurons to histaminergic and, for the first time, nonhistaminergic forms of itch stimuli. Fifty-seven primate spinothalamic tract (STT) neurons were identified using antidromic activation techniques and examined for their responses to histamine and cowhage, the nonhistaminergic itch-producing spicules covering the pod of the legume Mucuna pruriens. Each examined neuron had a receptive field on the hairy skin of the hindlimb and responded to noxious mechanical stimulation. STT neurons were tested with both pruritogens applied in a random order and we found 12 that responded to histamine and seven to cowhage. Each pruritogen-responsive STT neuron was activated by the chemical algogen capsaicin and two-thirds responded to noxious heat stimuli, demonstrating that these neurons convey chemical, thermal, and mechanical nociceptive information as well. Histamine or cowhage responsive STT neurons were found in both the marginal zone and the deep dorsal horn and were classified as high threshold and wide dynamic range. Unexpectedly, histamine and cowhage never activated the same cell. Our results demonstrate that the spinothalamic tract contains mutually exclusive populations of neurons responsive to histamine or the nonhistaminergic itch-producing agent cowhage. PMID:17855615

What is heartburn worth? A cost-utility analysis of management strategies.

Science.gov (United States)

Heudebert, G R; Centor, R M; Klapow, J C; Marks, R; Johnson, L; Wilcox, C M

2000-03-01

To determine the best treatment strategy for the management of patients presenting with symptoms consistent with uncomplicated heartburn. We performed a cost-utility analysis of 4 alternatives: empirical proton pump inhibitor, empirical histamine2-receptor antagonist, and diagnostic strategies consisting of either esophagogastroduodenoscopy (EGD) or an upper gastrointestinal series before treatment. The time horizon of the model was 1 year. The base case analysis assumed a cohort of otherwise healthy 45-year-old individuals in a primary care practice. Empirical treatment with a proton pump inhibitor was projected to provide the greatest quality-adjusted survival for the cohort. Empirical treatment with a histamine2 receptor antagonist was projected to be the least costly of the alternatives. The marginal cost-effectiveness of using a proton pump inhibitor over a histamine2-receptor antagonist was approximately $10,400 per quality-adjusted life year (QALY) gained in the base case analysis and was less than $50,000 per QALY as long as the utility for heartburn was less than 0.95. Both diagnostic strategies were dominated by proton pump inhibitor alternative. Empirical treatment seems to be the optimal initial management strategy for patients with heartburn, but the choice between a proton pump inhibitor or histamine2-receptor antagonist depends on the impact of heartburn on quality of life.

The Growth of Brown Adipose Tissue in Cold-acclimatized Rats after Depletion of Mast Cell Histamine by Compound 48/80

Directory of Open Access Journals (Sweden)

Daló Nelson L

1998-01-01

Full Text Available Cold acclimatization (4-5°C is accompanied by 2-3 fold increase of brown adipose tissue (BAT. This rapid growth of interscapular BAT was studied after histamine depletion. In control rats maintained at room temperature (28 ± 2°C the BAT histamine content was 23.4 ± 5.9 (mean ± SD µg/g of tissue and cold acclimatization (5±1°C produced a significant increase of BAT weight, but reduced the histamine content to 8.4 ± 1.9 µg/g. The total weight of BAT after 20 days of acclimatization was unaffected by depletion of histamine due to compound 48/80. The low level of histamine in BAT of cold acclimatized rats could be due to a fast rate of amine utilization; alternatively an altered synthesis or storage process may occur during acclimatization.

C-terminal of human histamine H1 receptors regulates their agonist-induced clathrin-mediated internalization and G-protein signaling.

Science.gov (United States)

Hishinuma, Shigeru; Nozawa, Hiroki; Akatsu, Chizuru; Shoji, Masaru

2016-11-01

It has been suggested that the agonist-induced internalization of G-protein-coupled receptors from the cell surface into intracellular compartments regulates cellular responsiveness. We previously reported that G q/11 -protein-coupled human histamine H 1 receptors internalized via clathrin-dependent mechanisms upon stimulation with histamine. However, the molecular determinants of H 1 receptors responsible for agonist-induced internalization remain unclear. In this study, we evaluated the roles of the intracellular C-terminal of human histamine H 1 receptors tagged with hemagglutinin (HA) at the N-terminal in histamine-induced internalization in Chinese hamster ovary cells. The histamine-induced internalization was evaluated by the receptor binding assay with [ 3 H]mepyramine and confocal immunofluorescence microscopy with an anti-HA antibody. We found that histamine-induced internalization was inhibited under hypertonic conditions or by pitstop, a clathrin terminal domain inhibitor, but not by filipin or nystatin, disruptors of the caveolar structure and function. The histamine-induced internalization was also inhibited by truncation of a single amino acid, Ser487, located at the end of the intracellular C-terminal of H 1 receptors, but not by its mutation to alanine. In contrast, the receptor-G-protein coupling, which was evaluated by histamine-induced accumulation of [ 3 H]inositol phosphates, was potentiated by truncation of Ser487, but was lost by its mutation to alanine. These results suggest that the intracellular C-terminal of human H 1 receptors, which only comprises 17 amino acids (Cys471-Ser487), plays crucial roles in both clathrin-dependent internalization of H 1 receptors and G-protein signaling, in which truncation of Ser487 and its mutation to alanine are revealed to result in biased signaling toward activation of G-proteins and clathrin-mediated internalization, respectively. © 2016 International Society for Neurochemistry.

Nascent histamine induces α-synuclein and caspase-3 on human cells

Energy Technology Data Exchange (ETDEWEB)

Caro-Astorga, Joaquín; Fajardo, Ignacio; Ruiz-Pérez, María Victoria; Sánchez-Jiménez, Francisca; Urdiales, José Luis, E-mail: jlurdial@uma.es

2014-09-05

Highlights: • Nascent histamine alters cyclin expression pattern. • Nascent histamine increases expression of α-synuclein. • Nascent histamine activates caspase-3. - Abstract: Histamine (Hia) is the most multifunctional biogenic amine. It is synthetized by histidine decarboxylase (HDC) in a reduced set of mammalian cell types. Mast cells and histaminergic neurons store Hia in specialized organelles until the amine is extruded by exocytosis; however, other immune and cancer cells are able to produce but not store Hia. The intracellular effects of Hia are still not well characterized, in spite of its physiopathological relevance. Multiple functional relationships exist among Hia metabolism/signaling elements and those of other biogenic amines, including growth-related polyamines. Previously, we obtained the first insights for an inhibitory effect of newly synthetized Hia on both growth-related polyamine biosynthesis and cell cycle progression of non-fully differentiated mammalian cells. In this work, we describe progress in this line. HEK293 cells were transfected to express active and inactive versions of GFP-human HDC fusion proteins and, after cell sorting by flow cytometry, the relative expression of a large number of proteins associated with cell signaling were measured using an antibody microarray. Experimental results were analyzed in terms of protein–protein and functional interaction networks. Expression of active HDC induced a cell cycle arrest through the alteration of the levels of several proteins such as cyclin D1, cdk6, cdk7 and cyclin A. Regulation of α-synuclein and caspase-3 was also observed. The analyses provide new clues on the molecular mechanisms underlying the regulatory effects of intracellular newly synthetized Hia on cell proliferation/survival, cell trafficking and protein turnover. This information is especially interesting for emergent and orphan immune and neuroinflammatory diseases.

Further studies on the structural requirements for mast cell degranulating (MCD) peptide-mediated histamine release.

Science.gov (United States)

Buku, A; Price, J A

2001-12-01

Mast cell degranulating (MCD) peptide was modified in its two disulfide bridges and in the two arginine residues in order to measure the ability of these analogs to induce histamine release from mast cells in vitro. Analogs prepared were [Ala(3,15)]MCD, [Ala(5,19)]MCD, [Orn(16)]MCD, and [Orn(7,16)]MCD. Their histamine-releasing activity was determined spectrofluorometrically with peritoneal mast cells. The monocyclic analogs in which the cysteine residues were replaced pairwise with alanine residues showed three-to ten-fold diminished histamine-releasing activity respectively, compared with the parent MCD peptide. Substantial increases in activity were observed where arginine residues were replaced by ornithines. The ornithine-mono substituted analog showed an almost six-fold increase and the ornithine-doubly substituted analog three-fold increase in histamine-releasing activity compared with the parent MCD peptide. The structural changes associated with these activities were followed by circular dichroism (CD) spectroscopy. Changes in the shape and ellipticity of the CD spectra reflected a role for the disulfide bonds and the two arginine residues in the overall conformation and biological activity of the molecule.

Endothelial Regulator of Calcineurin 1 Promotes Barrier Integrity and Modulates Histamine-Induced Barrier Dysfunction in Anaphylaxis

Directory of Open Access Journals (Sweden)

Constanza Ballesteros-Martinez

2017-10-01

Full Text Available Anaphylaxis, the most serious and life-threatening allergic reaction, produces the release of inflammatory mediators by mast cells and basophils. Regulator of calcineurin 1 (Rcan1 is a negative regulator of mast-cell degranulation. The action of mediators leads to vasodilation and an increase in vascular permeability, causing great loss of intravascular volume in a short time. Nevertheless, the molecular basis remains unexplored on the vascular level. We investigated Rcan1 expression induced by histamine, platelet-activating factor (PAF, and epinephrine in primary human vein (HV-/artery (HA-derived endothelial cells (ECs and human dermal microvascular ECs (HMVEC-D. Vascular permeability was analyzed in vitro in human ECs with forced Rcan1 expression using Transwell migration assays and in vivo using Rcan1 knockout mice. Histamine, but neither PAF nor epinephrine, induced Rcan1-4 mRNA and protein expression in primary HV-ECs, HA-ECs, and HMVEC-D through histamine receptor 1 (H1R. These effects were prevented by pharmacological inhibition of calcineurin with cyclosporine A. Moreover, intravenous histamine administration increased Rcan1 expression in lung tissues of mice undergoing experimental anaphylaxis. Functional in vitro assays showed that overexpression of Rcan1 promotes barrier integrity, suggesting a role played by this molecule in vascular permeability. Consistent with these findings, in vivo models of subcutaneous and intravenous histamine-mediated fluid extravasation showed increased response in skin, aorta, and lungs of Rcan1-deficient mice compared with wild-type animals. These findings reveal that endothelial Rcan1 is synthesized in response to histamine through a calcineurin-sensitive pathway and may reduce barrier breakdown, thus contributing to the strengthening of the endothelium and resistance to anaphylaxis. These new insights underscore its potential role as a regulator of sensitivity to anaphylaxis in humans.

Expression of histamine receptors in the human endolymphatic sac

DEFF Research Database (Denmark)

Møller, M Nue; Kirkeby, S; Vikeså, J.

2016-01-01

in 2012. This leaves betahistine (Betaserc) as the only drug for potential prevention of the incapacitating attacks of dizziness, tinnitus and hearing loss. However, the histamine receptors targeted by betahistine have never been demonstrated in the human ES. Accordingly, this study aims to investigate...

Carvacrol attenuates serum levels of total protein, phospholipase A2 and histamine in asthmatic guinea pig

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Mohammad Hossein Boskabady

2016-11-01

Full Text Available Objective: Pharmacological effects of carvacrol such as its anti-inflammatory activities have been shows. In this study the effects of carvacrol on serum levels of total protein (TP, phospholipase A2 (PLA2 and histamine in sensitized guinea pigs was evaluated. Materials and Methods: Sensitized guinea pigs were given drinking water alone (group S, drinking water containing three concentrations of carvacrol (40, 80 and 160 µg/ml or dexamethasone. Serum levels of TP, PLA2 and histamine were examined I all sensitized groups as well as a non-sensitized control group (n=6 for each group. Results: In sensitized animals, serum levels of TP, PLA2 and histamine were significantly increased compared to control animals (p

Docking-based Screening of Ficus religiosa Phytochemicals as Inhibitors of Human Histamine H2 Receptor.

Science.gov (United States)

Chaudhary, Amit; Yadav, Birendra Singh; Singh, Swati; Maurya, Pramod Kumar; Mishra, Alok; Srivastva, Shweta; Varadwaj, Pritish Kumar; Singh, Nand Kumar; Mani, Ashutosh

2017-10-01

Ficus religiosa L. is generally known as Peepal and belongs to family Moraceae . The tree is a source of many compounds having high medicinal value. In gastrointestinal tract, histamine H2 receptors have key role in histamine-stimulated gastric acid secretion. Their over stimulation causes its excessive production which is responsible for gastric ulcer. This study aims to screen the range of phytochemicals present in F. religiosa for binding with human histamine H2 and identify therapeutics for a gastric ulcer from the plant. In this work, a 3D-structure of human histamine H2 receptor was modeled by using homology modeling and the predicted model was validated using PROCHECK. Docking studies were also performed to assess binding affinities between modeled receptor and 34 compounds. Molecular dynamics simulations were done to identify most stable receptor-ligand complexes. Absorption, distribution, metabolism, excretion, and screening was done to evaluate pharmacokinetic properties of compounds. The results suggest that seven ligands, namely, germacrene, bergaptol, lanosterol, Ergost-5-en-3beta-ol, α-amyrin acetate, bergapten, and γ-cadinene showed better binding affinities. Among seven phytochemicals, lanosterol and α-amyrin acetate were found to have greater stability during simulation studies. These two compounds may be a suitable therapeutic agent against histamine H2 receptor. This study was performed to screen antiulcer compounds from F. religiosa . Molecular modeling, molecular docking and MD simulation studies were performed with selected phytochemicals from F. religiosa . The analysis suggests that Lanosterol and α-amyrin may be a suitable therapeutic agent against histamine H2 receptor. This study facilitates initiation of the herbal drug discovery process for the antiulcer activity. Abbreviations used: ADMET: Absorption, distribution, metabolism, excretion and toxicity, DOPE: Discrete Optimized Potential Energy, OPLS: Optimized potential for liquid

Effects of irradiation, antimicrobial agents and modified packaging on histamine production by Morganella morganii in mackerel fillets

International Nuclear Information System (INIS)

Aytac, S.A.; Ozbas, Z.Y.; Vural, H.

2000-01-01

The effects of gamma irradiation (0.5 and 2.0 kGy), antimicrobial agents (5% sodium chloride and 1% potassium sorbate) and modified atmosphere (100% CO2) packaging (MAP) on histamine production by Morganella morganii were examined in mackerel fillets during 8 days of cold storage. MAP combined with antimicrobial agents was also applied to the fillets. The changes in histamine levels, M. morganii and total aerobic bacterial counts were determined during the storage. All methods used in this study showed beneficial effect in controlling bacterial growth and histamine production on mackerel fillets during 2-3 days of storage. MAP combined with 5% sodium chloride has more retarding effect on production of histamine than the other methods. For M. morganii, maximum inhibition effect was found at the dose of 2.0 kGy. Irradiation with a dose of 2.0 kGy, MAP combined with sodium chloride and MAP were also found to have the most inhibiting effects on total aerobic bacterial count during the storage

The dynamics of histamine level in patients with chronic urticaria under the influence of different methods of treatment.

Directory of Open Access Journals (Sweden)

Dytyatkovska Ye.M.

2014-11-01

Full Text Available There was studied the efficiency of different methods of chronic urticaria treatment. All patients were divided into 2 groups depending on treatment scteme. The paper shows the dynamics of histamine level in blood plasma, intestine disbiosis in patients with chronic urticaria under the influence of different treatment complexes. It was proved that there exists the correlation between the serum histamine level and method of treatment. Intro¬ducing bionorm into the treatment allows to decrease histamine level and correspondingly to significantly improve clinical effect and patients’ life quality.

Liquid chromatography with luminol-based electrochemiluminescence detection determination of histamine

NARCIS (Netherlands)

Steijger, O.M.; Kamminga, D.A.; Brummelhuis, A.; Lingeman, H.

1998-01-01

The liquid chromatographic determination of histamine was achieved by precolumn derivatization with N-(4-aminobutyl)-N-ethylisoluminol isothiocyanate and electrochemiluminescence detection. Detection was carried out using postcolumn on-line electrochemical reagent generation and oxidation of the

A ROIC for Mn(TPP)Cl-DOP-THF-Polyhema PVC membrane modified n-channel Si3N4 ISFET sensitive to histamine.

Science.gov (United States)

Samah, N L M A; Lee, Khuan Y; Sulaiman, S A; Jarmin, R

2017-07-01

Intolerance of histamine could lead to scombroid poisoning with fatal consequences. Current detection methods for histamine are wet laboratory techniques which employ expensive equipment that depends on skills of seasoned technicians and produces delayed test analysis result. Previous works from our group has established that ISFETs can be adapted for detecting histamine with the use of a novel membrane. However, work to integrate ISFETs with a readout interfacing circuit (ROIC) circuit to display the histamine concentration has not been reported so far. This paper concerns the development of a ROIC specifically to integrate with a Mn(TPP)Cl-DOP-THF-Polyhema PVC membrane modified n-channel Si3N4 ISFET to display the histamine concentration. It embodies the design of constant voltage constant current (CVCC) circuit, amplification circuit and micro-controller based display circuit. A DC millivolt source is used to substitute the membrane modified ISFET as preliminary work. Input is histamine concentration corresponding to the safety level designated by the Food and Drugs Administration (FDA). Results show the CVCC circuit makes the output follows the input and keeps VDS constant. The amplification circuit amplifies the output from the CVCC circuit to the range 2.406-4.888V to integrate with the microcontroller, which is programmed to classify and display the histamine safety level and its corresponding voltage on a LCD panel. The ROIC could be used to produce direct output voltages corresponding to histamine concentrations, for in-situ applications.

Digoxigenin-histamine conjugates and their use in digoxin measurement

International Nuclear Information System (INIS)

1979-01-01

A method for measuring the digoxin content of a serum comprises adding to digoxin antibody coated tubes a mixture of a radiolabelled histamine derivative of digoxegenin and a sample, incubating the mixture to bind the antibody, separating the bound, labelled digoxin and measuring the radioactivity. (U.K.)

H4 histamine receptors mediate cell cycle arrest in growth factor-induced murine and human hematopoietic progenitor cells.

Directory of Open Access Journals (Sweden)

Anne-France Petit-Bertron

Full Text Available The most recently characterized H4 histamine receptor (H4R is expressed preferentially in the bone marrow, raising the question of its role during hematopoiesis. Here we show that both murine and human progenitor cell populations express this receptor subtype on transcriptional and protein levels and respond to its agonists by reduced growth factor-induced cell cycle progression that leads to decreased myeloid, erythroid and lymphoid colony formation. H4R activation prevents the induction of cell cycle genes through a cAMP/PKA-dependent pathway that is not associated with apoptosis. It is mediated specifically through H4R signaling since gene silencing or treatment with selective antagonists restores normal cell cycle progression. The arrest of growth factor-induced G1/S transition protects murine and human progenitor cells from the toxicity of the cell cycle-dependent anticancer drug Ara-C in vitro and reduces aplasia in a murine model of chemotherapy. This first evidence for functional H4R expression in hematopoietic progenitors opens new therapeutic perspectives for alleviating hematotoxic side effects of antineoplastic drugs.

The role of histamine in estradiol-induced conditioned consumption reductions.

Science.gov (United States)

Hintiryan, Houri; Hayes, Unja L; Chambers, Kathleen C

2005-01-31

Conditioned consumption reductions (CCRs) develop toward novel taste stimuli as a consequence of associating those tastes with certain physiological changes. Few studies have focused on the neurochemical basis of this learned behavior. The purpose of these experiments was to reexamine the role of histamine in CCRs elicited by estradiol. Previous studies have suggested that histamine mediates CCRs induced by radiation, centrifugal rotation, and estradiol. However, because the animals were trained in a drug state, but tested in a nondrug state, it is possible that state-dependent learning confounded the results of these studies. The following series of experiments was performed to test this possibility for estradiol-induced CCRs. Implementing our own methodologies in Experiment 1, we demonstrated that an estradiol-induced CCR was blocked by treatment with the histamine 1 receptor blocker, chlorpheniramine maleate, before sucrose consumption during acquisition. In Experiment 2, identical states were maintained during acquisition and extinction by administering chlorpheniramine prior to sucrose exposure during both phases. The results indicated that chlorpheniramine blocked the estradiol-induced CCR. However, circumventing state-dependency in Experiment 3 by administering chlorpheniramine following exposure to sucrose during acquisition augmented the estradiol CCR. Taken together, the results of these experiments suggest that the ability of chlorpheniramine to abolish estradiol-induced CCRs is not due to state-dependency or to the antihistaminergic properties of chlorpheniramine. It is proposed that the results of all of the experiments can be accounted for by the aversive properties of chlorpheniramine.

What Is Heartburn Worth?

Science.gov (United States)

Heudebert, Gustavo R; Centor, Robert M; Klapow, Joshua C; Marks, Robert; Johnson, Lawrence; Wilcox, C Mel

2000-01-01

OBJECTIVE T o determine the best treatment strategy for the management of patients presenting with symptoms consistent with uncomplicated heartburn. METHODS We performed a cost-utility analysis of 4 alternatives: empirical proton pump inhibitor, empirical histamine2-receptor antagonist, and diagnostic strategies consisting of either esophagogastroduodenoscopy (EGD) or an upper gastrointestinal series before treatment. The time horizon of the model was 1 year. The base case analysis assumed a cohort of otherwise healthy 45-year-old individuals in a primary care practice. MAIN RESULTS Empirical treatment with a proton pump inhibitor was projected to provide the greatest quality-adjusted survival for the cohort. Empirical treatment with a histamine2receptor antagonist was projected to be the least costly of the alternatives. The marginal cost-effectiveness of using a proton pump inhibitor over a histamine2-receptor antagonist was approximately $10,400 per quality-adjusted life year (QALY) gained in the base case analysis and was less than $50,000 per QALY as long as the utility for heartburn was less than 0.95. Both diagnostic strategies were dominated by proton pump inhibitor alternative. CONCLUSIONS Empirical treatment seems to be the optimal initial management strategy for patients with heartburn, but the choice between a proton pump inhibitor or histamine2-receptor antagonist depends on the impact of heartburn on quality of life. PMID:10718898

Cocaine Disrupts Histamine H3 Receptor Modulation of Dopamine D1 Receptor Signaling: σ1-D1-H3 Receptor Complexes as Key Targets for Reducing Cocaine's Effects

Science.gov (United States)

Moreno, Estefanía; Moreno-Delgado, David; Navarro, Gemma; Hoffmann, Hanne M.; Fuentes, Silvia; Rosell-Vilar, Santi; Gasperini, Paola; Rodríguez-Ruiz, Mar; Medrano, Mireia; Mallol, Josefa; Cortés, Antoni; Casadó, Vicent; Lluís, Carme; Ferré, Sergi; Ortiz, Jordi; Canela, Enric

2014-01-01

The general effects of cocaine are not well understood at the molecular level. What is known is that the dopamine D1 receptor plays an important role. Here we show that a key mechanism may be cocaine's blockade of the histamine H3 receptor-mediated inhibition of D1 receptor function. This blockade requires the σ1 receptor and occurs upon cocaine binding to σ1-D1-H3 receptor complexes. The cocaine-mediated disruption leaves an uninhibited D1 receptor that activates Gs, freely recruits β-arrestin, increases p-ERK 1/2 levels, and induces cell death when over activated. Using in vitro assays with transfected cells and in ex vivo experiments using both rats acutely treated or self-administered with cocaine along with mice depleted of σ1 receptor, we show that blockade of σ1 receptor by an antagonist restores the protective H3 receptor-mediated brake on D1 receptor signaling and prevents the cell death from elevated D1 receptor signaling. These findings suggest that a combination therapy of σ1R antagonists with H3 receptor agonists could serve to reduce some effects of cocaine. PMID:24599455

Localization and function of histamine H3 receptor in the nasal mucosa

OpenAIRE

Suzuki, Shinya; Takeuchi, Kazuhiko; Majima, Yuichi

2008-01-01

BACKGROUND: Histamine is an important chemical mediator of allergic rhinitis (AR). Histamine H3 receptors H3R are located on cholinergic and NANC neurons of the myenteric plexus, and activation of H3R regulates gastric acid secretion. However, little is known about the localization and function of H3R in the upper airway. OBJECTIVE: The objective of this study was to examine the localization and possible function of H3R in the nasal mucosa. METHODS: We extracted total RNA from the inferior tu...

The relationship between energy metabolism and the action of inhibitors of histamine release

DEFF Research Database (Denmark)

Garland, L G; Johansen, Torben

1977-01-01

1 Dextran-induced release of histamine from rat mast cells was inhibited equally in complete and glucose-free Tyrode solution by doxantrazole (0.03-3 micronmol/l), theophylline (0.1-3 mmol/l) and dicumarol (0.01-10 micronmol/litre). 2 Doxantrazole (3 micronmol/l), theophylline (3 mmol/l) and dicu......1 Dextran-induced release of histamine from rat mast cells was inhibited equally in complete and glucose-free Tyrode solution by doxantrazole (0.03-3 micronmol/l), theophylline (0.1-3 mmol/l) and dicumarol (0.01-10 micronmol/litre). 2 Doxantrazole (3 micronmol/l), theophylline (3 mmol...

Studies on the reduction of technetate(VII) by 1,2 bis(diphenylphosphino)ethane

International Nuclear Information System (INIS)

Muenze, R.; Seifert, S.; Kloetzer, D.; Maeding, P.; Goerner, W.

1984-01-01

The reduction of technetate(VII) by using 1,2 bis(diphenylphosphino)ethane (DPPE) has been investigated as a model for the preparation of new myotropic technetium compounds. Phosphino complexes were isolated and characterized which contain technetium in the oxidation state V([TcO 2 DPPE 2 ][TcO 4 ]), IV([TcCl 2 DPPE 2 ][TcCl 6 ]), III ([TcCl 3 DPPE 2 ] 0 ), ([TcCl 2 DPPE 2 ]Cl, and II ([TcCl 2 DPPE 2 ] 0 ) dependent on the reaction conditions, in particular Tc/DPPE and Tc/HCl ratios. (author)

Neurotensin is an antagonist of the human neurotensin NT2 receptor expressed in Chinese hamster ovary cells.

Science.gov (United States)

Vita, N; Oury-Donat, F; Chalon, P; Guillemot, M; Kaghad, M; Bachy, A; Thurneyssen, O; Garcia, S; Poinot-Chazel, C; Casellas, P; Keane, P; Le Fur, G; Maffrand, J P; Soubrie, P; Caput, D; Ferrara, P

1998-11-06

The human levocabastine-sensitive neurotensin NT2 receptor was cloned from a cortex cDNA library and stably expressed in Chinese hamster ovary (CHO) cells in order to study its binding and signalling characteristics. The receptor binds neurotensin as well as several other ligands already described for neurotensin NT1 receptor. It also binds levocabastine, a histamine H1 receptor antagonist that is not recognised by neurotensin NT1 receptor. Neurotensin binding to recombinant neurotensin NT2 receptor expressed in CHO cells does not elicit a biological response as determined by second messenger measurements. Levocabastine, and the peptides neuromedin N and xenin were also ineffective on neurotensin NT2 receptor activation. Experiments with the neurotensin NT1 receptor antagonists SR48692 and SR142948A, resulted in the unanticipated discovery that both molecules are potent agonists on neurotensin NT2 receptor. Both compounds, following binding to neurotensin NT2 receptor, enhance inositol phosphates (IP) formation with a subsequent [Ca2+]i mobilisation; induce arachidonic acid release; and stimulate mitogen-activated protein kinase (MAPK) activity. Interestingly, these activities are antagonised by neurotensin and levocabastine in a concentration-dependent manner. These activities suggest that the human neurotensin NT2 receptor may be of physiological importance and that a natural agonist for the receptor may exist.

The vascular permeabilizing factors histamine and serotonin induce angiogenesis through TR3/Nur77 and subsequently truncate it through thrombospondin-1

Science.gov (United States)

Qin, Liuliang; Zhao, Dezheng; Xu, Jianfeng; Ren, Xianghui; Terwilliger, Ernest F.; Parangi, Sareh; Lawler, Jack; Dvorak, Harold F.

2013-01-01

Angiogenesis plays an important role in cancer and in many other human diseases. Vascular endothelial growth factor-A (VEGF-A), the best known angiogenic factor, was originally discovered as a potent vascular permeability factor (VPF), suggesting that other vascular permeabilizing agents, such as histamine and serotonin, might also have angiogenic activity. We recently demonstrated that, like VEGF-A, histamine and serotonin up-regulate the orphan nuclear receptor and transcription factor TR3 (mouse homolog Nur77) and that TR3/Nur77 is essential for their vascular permeabilizing activities. We now report that histamine and serotonin are also angiogenic factors that, at low micromolar concentrations, induce endothelial cell proliferation, migration and tube formation in vitro, and angiogenesis in vivo. All of these responses are mediated through specific histamine and serotonin receptors, are independent of VEGF-A, and are directly dependent on TR3/Nur77. Initially, the angiogenic response closely resembled that induced by VEGF-A, with generation of “mother” vessels. However, after ∼10 days, mother vessels began to regress as histamine and serotonin, unlike VEGF-A, up-regulated the potent angiogenesis inhibitor thrombospondin-1, thereby triggering a negative feedback loop. Thus, histamine and serotonin induce an angiogenic response that fits the time scale of acute inflammation. PMID:23315169

培养液组胺的检测及鲣鱼产组胺菌的生物活性评价%Detection Histamine in Nutrient Solution and Evaluation of Biological Characteristics of Histamine-Forming Bacteria in Raw Skipjack Tuna

Institute of Scientific and Technical Information of China (English)

周秀锦; 杨建; 周向阳; 沈飚; 吴祖芳

2012-01-01

Histamine in nutrient solution is derived with dansyl chloride, determined by HPLC-VWD and quantified by isotope internal standard method with 1,7-Diaminoheptane. Histamine-forming bacteria were selected from the prescreening step using Actis＇s identification medium from skipjack tuna tissue, and true his-tamine formers were confirmed by HPLC method. Effects of temperature and pH on growth and histamine pro-duction of histamine-forming bacteria were studied. The results showed that the limit of determination of the method for nutrient solution is 0.5μg/mL, the recovery range is 100%-107%; two histamine formers isolated from skipjack tuna tissue were named as J2 and J4, which could produced histamine in trypticase soy broth supplemented with 1.0% L-histidine. The optimal temperature of growth of them were both 30 ℃, and the op- timal growth pH were 7 and 6, respectively. The optimal temperature of histamine production of them were 25 ℃ and 30 ℃, respectively. The optimal pH were both 5. The maximum of histamine reached 12.47 mg/L under the suitable culture condition.%通过直接将培养液中的组胺经丹酰氯衍生化生成稳定的物质,以1,7-二氨基庚烷为内标,建立高效液相色谱-紫外检测器（HPLC-VWD）方法检测培养液中的组胺;并研究了温度和pH对产组胺菌生长和组胺产生的影响。结果表明,培养液中组胺的检测方法定量限为0.5μg/mL,回收率在100%～107%,满足方法培养液中组胺的检测。经分离得到的2株产组胺菌分别记为J2和J4,2株菌在添加L-组氨酸的胰酶大豆肉汤里均能够产生组胺;菌株J2和J4最适生长温度均为30℃,最适pH分别为7和6,菌株J2和J4产组胺的最适温度分别为25℃和30℃,最适pH均为5,在适宜的实验条件下组胺产生量最大值为12.47 mg/L。

Utilization of Diamine Oxidase Enzyme from Mung Bean Sprouts (Vigna radiata L) for Histamine biosensors

Science.gov (United States)

Karim, Abdul; Wahab, A. W.; Raya, I.; Natsir, H.; Arif, A. R.

2018-03-01

This research is aimed to utilize the diamine oxidase enzyme (DAO) which isolated from mung bean sprouts (Vigna radiata L) to develop histamine biosensors based on electode enzyme with the amperometric method (cyclic voltammetry).The DAO enzyme is trapped inside the membrane of chitin-cellulose acetate 2:1 and glutaraldehyde which super imposed on a Pt electrode. Histamine will be oxidized by DAO enzyme to produce aldehydes and H2O2 that acting as electron transfer mediators.The performance of biosensors will be measured at various concentrations of glutaraldehyde, temperature changes and different range of pH. Recently, it has been found that the optimal conditions obtained from the paramaters as follows; at 25% of glutaraldehyde, temperature of 37°C and pH of 7.4. Eventually, the results provided an expectation for applying histamine biosensors in determining the freshness and safety of fish specifically skombroidae families.

Is a positive intracutaneous test induced by penicillin mediated by histamine?

DEFF Research Database (Denmark)

Tannert, Line K; Falkencrone, Sidsel; Mortz, Charlotte G

2017-01-01

Background: Diagnostic workup of penicillin allergy comprises skin testing with penicillins, and patients are deemed allergic if skin test is positive. However, the literature suggests that skin test-positive patients may be challenge-negative, indicating that the skin test may be falsely positive....... Objective: To investigate real-time histamine release from a positive intracutaneous test induced by penicillin in patients with positive and negative challenges to penicillin. Methods: Skin microdialysis was performed in 21 penicillin-allergic patients with positive skin test, 13 non-allergic volunteers...... serving as negative controls, and 7 grass pollen-allergic patients serving as positive controls. Histamine was measured by microdialysis after skin test with penicillin/grass/NaCl. Penicillin challenge was subsequently performed in 12 of the patients. Results: Only 10/21 patients (47.6%) were skin test...

Mutations in the histamine N-methyltransferase gene, HNMT, are associated with nonsyndromic autosomal recessive intellectual disability

OpenAIRE

Heidari, Abolfazl; Tongsook, Chanakan; Najafipour, Reza; Musante, Luciana; Vasli, Nasim; Garshasbi, Masoud; Hu, Hao; Mittal, Kirti; McNaughton, Amy J. M.; Sritharan, Kumudesh; Hudson, Melissa; Stehr, Henning; Talebi, Saeid; Moradi, Mohammad; Darvish, Hossein

2015-01-01

Histamine (HA) acts as a neurotransmitter in the brain, which participates in the regulation of many biological processes including inflammation, gastric acid secretion and neuromodulation. The enzyme histamine N-methyltransferase (HNMT) inactivates HA by transferring a methyl group from S-adenosyl-l-methionine to HA, and is the only well-known pathway for termination of neurotransmission actions of HA in mammalian central nervous system. We performed autozygosity mapping followed by targeted...

Complexity of the influence of gangliosides on histamine release from human basophils and rat mast cells

DEFF Research Database (Denmark)

Jensen, C; Svendsen, U G; Thastrup, Ole

1987-01-01

The influence of exogenous addition of gangliosides on histamine release from human basophils and rat mast cells was examined in vitro. Gangliosides dose-dependently inhibited histamine release, and this inhibition was dependent on the ganglioside sialic acid content, since GT1b, having 3 sialic...... was reflected in the sensitivity of the cells to extracellular calcium, since inhibition of the release could be counteracted by increasing the extracellular concentration of calcium....

Waking action of ursodeoxycholic acid (UDCA involves histamine and GABAA receptor block.

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Yevgenij Yanovsky

Full Text Available Since ancient times ursodeoxycholic acid (UDCA, a constituent of bile, is used against gallstone formation and cholestasis. A neuroprotective action of UDCA was demonstrated recently in models of Alzheimer's disease and retinal degeneration. The mechanisms of UDCA action in the nervous system are poorly understood. We show now that UDCA promotes wakefulness during the active period of the day, lacking this activity in histamine-deficient mice. In cultured hypothalamic neurons UDCA did not affect firing rate but synchronized the firing, an effect abolished by the GABA(AR antagonist gabazine. In histaminergic neurons recorded in slices UDCA reduced amplitude and duration of spontaneous and evoked IPSCs. In acutely isolated histaminergic neurons UDCA inhibited GABA-evoked currents and sIPSCs starting at 10 µM (IC(50 = 70 µM and did not affect NMDA- and AMPA-receptor mediated currents at 100 µM. Recombinant GABA(A receptors composed of α1, β1-3 and γ2L subunits expressed in HEK293 cells displayed a sensitivity to UDCA similar to that of native GABA(A receptors. The mutation α1V256S, known to reduce the inhibitory action of pregnenolone sulphate, reduced the potency of UDCA. The mutation α1Q241L, which abolishes GABA(AR potentiation by several neurosteroids, had no effect on GABA(AR inhibition by UDCA. In conclusion, UDCA enhances alertness through disinhibition, at least partially of the histaminergic system via GABA(A receptors.

Inhibition of histamine and eicosanoid release from dispersed human lung cells in vitro by quinotolast.

Science.gov (United States)

Okayama, Y; Hiroi, J; Lau, L C; Church, M K

1995-12-01

We have examined the effects of a new anti-allergic drug, quinotolast [sodium 5-(4-oxo-1-phenoxy-4H-quinolizine-3-carboxamido) yetrazolate monohydrate], in inhibiting the release of histamine and the generation of leukotriene (LT) C4 and prostaglandin (PG) D2 from dispersed human lung cells and compared this with those of its active metabolite in the rat, hydroxy quinotolast, and reference drugs, tranilast and sodium cromoglycate (SCG). Quinotolast in the concentration range of 1-100 micrograms/ml inhibited histamine and LTC4 release in a concentration-dependent manner. The inhibitory effect of quinotolast on histamine release from dispersed lung cells was largely independent of the preincubation period, no tachyphylaxis being observed. Hydroxy quinotolast and tranilast showed a weak inhibition of histamine release only when the drugs were added to the cells simultaneously with anti-IgE challenge. Quinotolast, 100 micrograms/ml, and SCG, 1 mM, significantly inhibited PGD2 and LTC4 release. Quinotolast inhibited PGD2 release by 100% and LTC4 release by 54%, whereas SCG inhibited PDG2 release by 33% and LTC4 release by 100%. No cross-tachyphylaxis between quinotolast and SCG was observed. The results demonstrated that quinotolast showed a significant inhibition of inflammatory mediators from human dispersed lung cells, suggesting that quinotolast is a good candidate for a clinical anti-allergic drug.

Histamine Enhances Theta-Coupled Spiking and Gamma Oscillations in the Medial Entorhinal Cortex Consistent With Successful Spatial Recognition.

Science.gov (United States)

Chen, Quanhui; Luo, Fenlan; Yue, Faguo; Xia, Jianxia; Xiao, Qin; Liao, Xiang; Jiang, Jun; Zhang, Jun; Hu, Bo; Gao, Dong; He, Chao; Hu, Zhian

2017-06-07

Encoding of spatial information in the superficial layers of the medial entorhinal cortex (sMEC) involves theta-modulated spiking and gamma oscillations, as well as spatially tuned grid cells and border cells. Little is known about the role of the arousal-promoting histaminergic system in the modification of information encoded in the sMEC in vivo, and how such histamine-regulated information correlates with behavioral functions. Here, we show that histamine upregulates the neural excitability of a significant proportion of neurons (16.32%, 39.18%, and 52.94% at 30 μM, 300 μM, and 3 mM, respectively) and increases local theta (4-12 Hz) and gamma power (low: 25-48 Hz; high: 60-120 Hz) in the sMEC, through activation of histamine receptor types 1 and 3. During spatial exploration, the strength of theta-modulated firing of putative principal neurons and high gamma oscillations is enhanced about 2-fold by histamine. The histamine-mediated increase of theta phase-locking of spikes and high gamma power is consistent with successful spatial recognition. These results, for the first time, reveal possible mechanisms involving the arousal-promoting histaminergic system in the modulation of spatial cognition. Published by Oxford University Press 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Inhibition of neurotensin-stimulated mast cell secretion and carboxypeptidase A activity by the peptide inhibitor of carboxypeptidase A and neurotensin-receptor antagonist SR 48692.

Science.gov (United States)

Miller, L A; Cochrane, D E; Feldberg, R S; Carraway, R E

1998-06-01

Neurotensin (NT), a peptide found in brain and several peripheral tissues, is a potent stimulus for mast cell secretion and its actions are blocked by the specific NT receptor antagonist, SR 48692. Subsequent to stimulation, NT is rapidly degraded by mast cell carboxypeptidase A (CPA). In the experiments described here, we tested for the involvement of CPA activity in the activation of mast cell secretion by the peptide, NT. Mast cells were isolated from the peritoneal and pleural cavities of rats, purified over metrizamide gradients and incubated at 37 degrees C in Locke solution or Locke containing the appropriate inhibitors. For some experiments, media derived from mast cells stimulated by compound 48/80 were used as a source of mast cell CPA activity. Treatment of mast cells with the highly specific peptide inhibitor of CPA derived from potato (PCI) inhibited histamine release in response to NT and NT8-13 (the biologically active region of NT). This inhibition required some 20 min to develop and was only partially reversed by a 20-min wash period. PCI (10 microM) did not inhibit histamine release in response to NT1-12, bradykinin, compound 48/80, the calcium ionophore, A23187, or anti-IgE serum. PCI also inhibited mast cell CPA activity. SR 48692, a highly selective antagonist of the brain NT receptor and of NT-stimulated mast cell secretion, also inhibited mast cell CPA activity as well as bovine pancreatic CPA activity in a concentration-dependent manner. It is suggested that the mast cell binding site for NT and the active site for CPA may share similar characteristics. The results are discussed in terms of NT mechanism of action on the mast cell.

Two randomised phase II trials of subcutaneous interleukin-2 and histamine dihydrochloride in patients with metastatic renal cell carcinoma

DEFF Research Database (Denmark)

Donskov, F; Middleton, M; Fode, K

2005-01-01

Histamine inhibits formation and release of phagocyte-derived reactive oxygen species, and thereby protects natural killer and T cells against oxidative damage. Thus, the addition of histamine may potentially improve the efficacy of interleukin-2 (IL-2). Two randomised phase II trials of IL-2...... per week for 3 weeks followed by 2 weeks rest. Histamine dihydrochloride was added twice daily, 1.0 mg s.c., concomitantly with IL-2. A maximum of four cycles were given. The Danish study showed a statistically significant 1-year survival benefit (76 vs 47%, P = 0.03), a trend towards benefit in both...

Effect of exposure to O/sub 3/, SO/sub 2/, and NO/sub 2/ upon the lung histamine content of guinea pigs

Energy Technology Data Exchange (ETDEWEB)

Suzuki, T

1969-01-01

Male guinea pigs were exposed to 1 or 4 to 8 ppM O/sub 3/, 10 or 50 ppM SO/sub 2/, or 10 or 80 ppM NO/sub 2/ for 3 hr. Histamine and water content of lungs were measured. Animals exposed to higher concentrations of O/sub 3/ or NO/sub 2/ had edematous lungs. Lungs of those exposed to lower concentrations of O/sub 3/ or NO/sub 2/ also had slightly higher water contents. Lung histamine content and concentration decreased by O/sub 3/ exposure but not by any other treatment. In vitro exposure of lung to O/sub 3/ showed released histamine occurring in the perfusion outflow. Endogenous, cellular, inert histamine evidently was released by O/sub 3/ stimulant. However, the mechanism for NO/sub 2/-caused edema was not revealed, but could be direct action on lung vessels rather than through histamine mediation.

Histamine release from cord blood basophils

DEFF Research Database (Denmark)

Nielsen, Bent Windelborg; Damsgaard, Tine Engberg; Herlin, Troels

1990-01-01

The histamine release (HR) after challenge with anti-IgE, concanavalin A, N-formyl-met-leu-phe and the calcium ionophore A23187 from 97 cord blood samples was determined by a microfiber-based assay. Maximum HR with anti-IgE showed great inter-individual variation (median: 20.5; range: 1-104 ng...... of less than 0.5 IU/ml, although sensitivity to anti-IgE was universally increased. Preincubation with pharmacologic agents modulating the IgE-mediated HR produced effects generally similar to previous findings in adult blood. However, the effects of inhibiting the cyclooxygenase pathway in cord blood...

Histaminergic system in brain disorders: lessons from the translational approach and future perspectives.

Science.gov (United States)

Baronio, Diego; Gonchoroski, Taylor; Castro, Kamila; Zanatta, Geancarlo; Gottfried, Carmem; Riesgo, Rudimar

2014-01-01

Histamine and its receptors were first described as part of immune and gastrointestinal systems, but their presence in the central nervous system and importance in behavior are gaining more attention. The histaminergic system modulates different processes including wakefulness, feeding, and learning and memory consolidation. Histamine receptors (H1R, H2R, H3R, and H4R) belong to the rhodopsin-like family of G protein-coupled receptors, present constitutive activity, and are subjected to inverse agonist action. The involvement of the histaminergic system in brain disorders, such as Alzheimer's disease, schizophrenia, sleep disorders, drug dependence, and Parkinson's disease, is largely studied. Data obtained from preclinical studies point antagonists of histamine receptors as promising alternatives to treat brain disorders. Thus, clinical trials are currently ongoing to assess the effects of these drugs on humans. This review summarizes the role of histaminergic system in brain disorders, as well as the effects of different histamine antagonists on animal models and humans.

Effect of ouabain, digoxin and digitoxigenin on potassium uptake and histamine release from rat peritoneal mast cells

DEFF Research Database (Denmark)

Knudsen, T; Ferjan, I; Johansen, Torben

1993-01-01

Rat peritoneal mast cells were used to study the effects of digitalis glycosides on potassium uptake and histamine release induced by compound 48/80, substance P and egg-albumin (immunological release). In the absence of calcium all glycosides inhibited potassium uptake. Ouabain and digoxin....... Hydrophilic digitalis glycosides seem to enhance histamine release secondary to an increase in intracellular sodium. Lipophilic glycosides have no effect on the release....

Histamine H1 receptors are expressed in mouse and frog semicircular canal sensory epithelia.

Science.gov (United States)

Botta, Laura; Tritto, Simona; Perin, Paola; Laforenza, Umberto; Gastaldi, Giulia; Zampini, Valeria; Zucca, Gianpiero; Valli, Stefano; Masetto, Sergio; Valli, Paolo

2008-03-05

Histamine-related drugs are commonly used in the treatment of vertigo and related vestibular disorders. Their site and mechanism of action, however, are still poorly understood. To increase our knowledge of the histaminergic system in the vestibular organs, we have investigated the expression of H1 and H3 histamine receptors in the frog and mouse semicircular canal sensory epithelia. Analysis was performed by mRNA reverse transcriptase-PCR, immunoblotting and immunocytochemistry experiments. Our data show that both frog and mouse vestibular epithelia express H1 receptors. Conversely no clear evidence for H3 receptors expression was found.

Effect of the histaminergic antagonist over the pulmonary oedema growth in P. berghei - infected mice

International Nuclear Information System (INIS)

Martins, M.A.

1985-01-01

The involvement of histaminergic mechanisms in the pathogenesis of pulmonary oedema observed in p. berghei - infected mice was investigated. Histamine concentrations in plasma and whole blood of infected and normal mice were determined by radioenzymatic assay during the seven days of the infection. Elevated plasma and whole blood histamine levels were found at the last stages of infection (sixth day and seventh day) after intraperitoneal injection of parasitized erythrocytes, showing a close temporal correlation between the development of the oedema and the elevation of the circulating histamine concentrations. The participation of H 1 and H 2 receptors in the increase in vascular permeability (IVP) induced by histamine was also verified. (author)

Binding mechanisms for histamine and agmatine ligands in plasmid deoxyribonucleic acid purifications.

Science.gov (United States)

Sousa, Ângela; Pereira, Patrícia; Sousa, Fani; Queiroz, João A

2014-10-31

Histamine and agmatine amino acid derivatives were immobilized into monolithic disks, in order to combine the specificity and selectivity of the ligand with the high mass transfer and binding capacity offered by monolithic supports, to purify potential plasmid DNA biopharmaceuticals. Different elution strategies were explored by changing the type and salt concentration, as well as the pH, in order to understand the retention pattern of different plasmids isoforms The pVAX1-LacZ supercoiled isoform was isolated from a mixture of pDNA isoforms by using NaCl increasing stepwise gradient and also by ammonium sulfate decreasing stepwise gradient, in both histamine and agmatine monoliths. Acidic pH in the binding buffer mainly strengthened ionic interactions with both ligands in the presence of sodium chloride. Otherwise, for histamine ligand, pH values higher than 7 intensified hydrophobic interactions in the presence of ammonium sulfate. In addition, circular dichroism spectroscopy studies revealed that the binding and elution chromatographic conditions, such as the combination of high ionic strength with extreme pH values can reversibly influence the structural stability of the target nucleic acid. Therefore, ascending sodium chloride gradients with pH manipulation can be preferable chromatographic conditions to be explored in the purification of plasmid DNA biopharmaceuticals, in order to avoid the environmental impact of ammonium sulfate. Copyright © 2014. Published by Elsevier B.V.

Temporal responses of cutaneous blood flow and plasma catecholamine concentrations to histamine H1- or H2-receptor stimulation in man

DEFF Research Database (Denmark)

Knigge, U; Alsbjørn, B; Thuesen, B

1988-01-01

continuously with a laser Doppler flowmeter, and noradrenaline and adrenaline concentrations were determined in blood samples drawn every 15 min. The infusion of histamine caused an immediate and sustained vasodilatation. The Concomitant infusion of mepyramine prevented the immediate vasodilatation, but had...... noradrenaline, while the increase during concomitant H1-receptor blockade was delayed but achieved the level observed during the histamine infusion. The response to histamine during H2-receptor blockade was small and transient. The rise in plasma adrenaline was not significant. These findings suggest...

Effects of antihistamines on innate immune responses to severe bacterial infection in mice

DEFF Research Database (Denmark)

Metz, Martin; Doyle, Elizabeth; Bindslev-Jensen, Carsten

2011-01-01

Sedating and non-sedating histamine H(1) receptor (H1R) antagonists and H2R blockers are widely used drugs which are generally considered to be safe medications. However, recently, these drugs have been shown to possibly impair the outcome of perforating appendicitis in children.......Sedating and non-sedating histamine H(1) receptor (H1R) antagonists and H2R blockers are widely used drugs which are generally considered to be safe medications. However, recently, these drugs have been shown to possibly impair the outcome of perforating appendicitis in children....

Generation of a Proton Motive Force by Histidine Decarboxylation and Electrogenic Histidine/Histamine Antiport in Lactobacillus buchneri

OpenAIRE

Molenaar, Douwe; Bosscher, Jaap S.; Brink, Bart ten; Driessen, Arnold J.M.; Konings, Wil N.

1993-01-01

Lactobacillus buchneri ST2A vigorously decarboxylates histidine to the biogenic amine histamine, which is excreted into the medium. Cells grown in the presence of histidine generate both a transmembrane pH gradient, inside alkaline, and an electrical potential (delta psi), inside negative, upon addition of histidine. Studies of the mechanism of histidine uptake and histamine excretion in membrane vesicles and proteoliposomes devoid of cytosolic histidine decarboxylase activity demonstrate tha...

Lowering histamine formation in a red Ribera del Duero wine (Spain) by using an indigenous O. oeni strain as a malolactic starter.

Science.gov (United States)

Berbegal, Carmen; Benavent-Gil, Yaiza; Navascués, Eva; Calvo, Almudena; Albors, Clara; Pardo, Isabel; Ferrer, Sergi

2017-03-06

This study demonstrates for the first time that a non-commercial selected autochthonous O. oeni strain has been used to conduct malolactic fermentation (MLF) while lowering histamine formation in the same winery. Lactic acid bacteria (LAB) were isolated from 13 vats before and after spontaneous MLF at the Pago de Carraovejas winery from the Ribera del Duero region (Spain). Only O. oeni were present, typed and characterized, and both histamine producer and non-producers existed. From the non-producers, one strain was selected to become a starter according to its genetic profile, prevalence in the different wines in the winery, resistance to alcoholic degree, resistance to high polyphenolic content, inability to synthesise histamine, growth kinetics and malolactic activity. This starter was produced at semi-industrial levels to inoculate 20,000L of Tempranillo red wine. The inoculated vat showed 5-fold less histamine than the non-inoculated control vat. After 1year, the barrel-ageing histamine concentrations were 3-fold lower in the inoculated vat than in the non-inoculated vat. Copyright © 2016 Elsevier B.V. All rights reserved.

Validation of high-performance liquid chromatography (HPLC method for quantitative analysis of histamine in fish and fishery products

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B.K.K.K. Jinadasa

2016-12-01

Full Text Available A high-performance liquid chromatography method is described for quantitative determination and validation of histamine in fish and fishery product samples. Histamine is extracted from fish/fishery products by homogenizing with tri-chloro acetic acid, separated with Amberlite CG-50 resin and C18-ODS Hypersil reversed phase column at ambient temperature (25°C. Linear standard curves with high correlation coefficients were obtained. An isocratic elution program was used; the total elution time was 10 min. The method was validated by assessing the following aspects; specificity, repeatability, reproducibility, linearity, recovery, limits of detection, limit of quantification and uncertainty. The validated parameters are in good agreement with method and it is a useful tool for determining histamine in fish and fishery products.

Histamine release from gut mast cells from patients with inflammatory bowel diseases

DEFF Research Database (Denmark)

Nolte, Hendrik; Spjeldnæs, Nikolaj; Kruse, Aksel

1990-01-01

Inflammatory mediators from intestinal mast cells may serve as initiators of acute and delayed inflammation. Mast cell histamine release was measured in 19 patients with inflammatory bowel diseases using gut mast cells from enzymatically dispersed endoscopic forceps biopsy specimens...... of macroscopically inflamed and normal tissue. Mast cells and corresponding basophils were challenged with anti-IgE, anti-IgG, subclass anti-IgG4, and formyl-methionyl-leucyl-phenylalanine (FMLP) and results were compared with those from nine patient control subjects. The mast cell count in patients with ulcerative...... colitis was increased compared with that in control subjects and patients with Crohn's disease, and the mast cell count obtained from inflamed tissue was greater than that of normal tissue. The study also shows the heterogeneity of the responsiveness of the histamine releasing cells to various...

Develop and validation of an analytic method for the histamine determination in fish, using chromatography liquidates of high efficiency in reverse phase with ultraviolet detection

International Nuclear Information System (INIS)

Valverde Chavarria, J. C.

1997-01-01

There were determined and optimized the reaction and conditions analysis, for the derivation of the histamine with the reagent of or-ftalaldehido (OPA), it was proven that it is possible to quantify the one derived formed at 333nm. The good conditions crhomatografics settled down for the determination of the histamine in fish by means of the analytic technique of chromatography it liquidates of high efficiency (HPLC) in reverse phase, using the derivatizacion in precolumn of the histamine with the reagent of OPA, with ultraviolet detection at 333nm. The conditions of the proposed methodology were optimized and the variables of analytic acting were validated, for the analytic quantification of the histamine in the mg g-1 environment. The applicability of the methodology was demonstrated in the histamine determination in samples of fresh fish [es

Energy metabolism in rat mast cells in relation to histamine secretion

DEFF Research Database (Denmark)

Johansen, T

1987-01-01

1. The relation between the energy metabolism and the secretory activity of rat peritoneal mast cells has been studied by determination of the cellular content of ATP and the rate of lactate production reflecting the rate of ATP synthesis under various experimental conditions. Secretion...... and the cellular ATP content at the time of cell activation was demonstrated. This may indicate a direct link between ATP and the secretory mechanism. 3. The possibility of an increased utilization of ATP during histamine secretion was explored in mast cells exposed to metabolic inhibitors. Incubation of mast...... cells with 2-deoxyglucose (2-DG) decreased the ATP content of the cells, and a long-lasting and stable level of mast cell ATP was observed. This is explained by a small decrease in the rate of ATP-synthesis by 2-DG. In 2-DG-treated cells secretion of histamine in response to compound 48...

Influence of nitric oxide on histamine and carbachol – induced ...

African Journals Online (AJOL)

The study aimed to determine the influence of nitric oxide (NO) on the action of histamine and carbachol on acid secretion in the common African toad – Bufo regularis. Gastric acidity was determined by titration method. The acid secretion was determined when nitric oxide was absent following administration of NO synthase ...

Histamine Regulates the Inflammatory Profile of SOD1-G93A Microglia and the Histaminergic System Is Dysregulated in Amyotrophic Lateral Sclerosis

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Savina Apolloni

2017-11-01

Full Text Available Amyotrophic lateral sclerosis (ALS is a late-onset motor neuron disease where activated glia release pro-inflammatory cytokines that trigger a vicious cycle of neurodegeneration in the absence of resolution of inflammation. Given the well-established role of histamine as a neuron-to-glia alarm signal implicated in brain disorders, the aim of this study was to investigate the expression and regulation of the histaminergic pathway in microglial activation in ALS mouse model and in humans. By examining the contribution of the histaminergic system to ALS, we found that particularly via H1 and H4 receptors, histamine promoted an anti-inflammatory profile in microglia from SOD1-G93A mice by modulating their activation state. A decrease in NF-κB and NADPH oxidase 2 with an increase in arginase 1 and P2Y12 receptor was induced by histamine only in the ALS inflammatory environment, but not in the healthy microglia, together with an increase in IL-6, IL-10, CD163, and CD206 phenotypic markers in SOD1-G93A cells. Moreover, histaminergic H1, H2, H3, and H4 receptors, and histamine metabolizing enzymes histidine decarboxylase, histamine N-methyltransferase, and diamine oxidase were found deregulated in spinal cord, cortex, and hypothalamus of SOD1-G93A mice during disease progression. Finally, by performing a meta-analysis study, we found a modulated expression of histamine-related genes in cortex and spinal cord from sporadic ALS patients. Our findings disclose that histamine acts as anti-inflammatory agent in ALS microglia and suggest a dysregulation of the histaminergic signaling in ALS.

Histamine-imprinted microspheres: Comparison between conventional and raft-mediated polymerization techniques

International Nuclear Information System (INIS)

Romano, Edwin F. Jr.; So, Regina C.; Holdsworth, Clovia I.

2015-01-01

Molecularly imprinted microspheres (MIM) were synthesized via conventional free radical polymerization (CTP) and RAFT-mediated controlled radical polymerization (CRP) method using histamine as the template molecule. Optimal polymerization conditions were achieved using 4%(w/w) monomer feed concentration with 80=90% EGDMA as crosslinker, and histamine: MAA ratio of 1:4 in acetonitrile at 60°C for 24 hours. The size of CTP-M90 and CTP-M80 imprinted microspheres are comparable with that of RAFT polymer CRP-M80 at 264.5 ±12 nm in the swollen (DLS-DMSO) and collapsed state (SEM). For the CTP method, the presence of the template allows for a bigger particle size compared to the non-imprinted counterpart (NIM). Further, controlled growth was observed for the CRP technique, where the size of the imprinted microsphere, CRP-M80, is comparable to CRP-N80. The binding studies of CTP and CRP microspheres toward histamine were studied at concentrations well below biding with buffer concentration of 25mM at pH7. Results showed that the binding isotherms were found to conform to the Freundlich model. Moreover, results revealed that the difference in binding capacity (N) between MIM and NIM imparted by the imprinting process is significantly higher in CTP-80 (26 μmol/g) than both CTP-90 and CRP-80 (9 μmol/g). Non-competitive and competitive binding assays with L-histidine, imidazole, and tryptamine using CTP-80 and CRP-80 were also carried out. MIMs were shown to exhibit binding preference towards the template. (author)

Down-regulation of histamine-induced endothelial cell activation as potential anti-atherosclerotic activity of peptides from Spirulina maxima.

Science.gov (United States)

Vo, Thanh-Sang; Kim, Se-Kwon

2013-10-09

Histamine, a potent inflammatory mediator, has been known to cause the pathogenesis of atherosclerosis. In this sense, two bioactive peptides P1 (LDAVNR; 686Da) and P2 (MMLDF; 655Da) purified from gastric enzymatic hydrolysate of Spirulina maxima were examined for their protective effects against early atherosclerotic responses induced by histamine in EA.hy926 endothelial cells. Interestingly, both P1 and P2 exhibited inhibitory activities on the production and expression of IL-6 and MCP-1. Furthermore, P1 and P2 inhibited the production of adhesion molecules including P-selectin and E-selectin, and thus reducing in vitro cell adhesion of monocyte onto endothelial cells. In addition, the production of intracellular reactive oxygen species was observed to reduce in the presence of P1 or P2. Notably, the inhibitory activities of P1 and P2 were found due to down-regulating Egr-1 expression via histamine receptor and PKCδ-dependent MAPKs activation pathway. These results suggest that peptides P1 and P2 from S. maxima are effective to suppress histamine-induced endothelial cell activation that may contribute to the prevention of early atherosclerosis. Copyright © 2013 Elsevier B.V. All rights reserved.

Histamine and TNF-α release by rat peritoneal mast cells stimulated with Trichomonas vaginalis

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Im S.J.

2011-02-01

Full Text Available Mast cells have been reported to be predominant in the vaginal smears of patients infected with T. vaginalis. In this study, we investigated whether T. vaginalis could induce mast cells to migrate and to produce TNF-α and histamine. Rat peritoneal mast cells (RPMC, a primary mast cell, were used for the study. T. vaginalis induced an increase in chemotactic migration of the mast cells toward excretory and secretory product (ESP of T. vaginalis, and the mast cells activated with T. vaginalis showed an increased release of histamine and TNF-α. Therefore, mast cells may be involved in the inflammatory response caused by T. vaginalis.

The utilization of adenosine triphosphate in rat mast cells during histamine release induced by anaphylactic reaction and compound 48/80

DEFF Research Database (Denmark)

Johansen, Torben; Chakravarty, N

1975-01-01

of ATP synthesis while a large part of the histamine release remained unaffected-a decrease in the ATP content could be demonstrated in close time relation to both anaphylactic and compound 48/80-induced histamine release. The observations indicate an increased utilization of ATP in mast cells during...

Time-dependent histamine release from stored human blood products

DEFF Research Database (Denmark)

Nielsen, Hans Jørgen; Edvardsen, L; Vangsgaard, K

1996-01-01

.0 (range 176.0-910.0) nmol/l in whole blood and 475.0 (range 360.0-1560.0) nmol/l in plasma-reduced whole blood, while it was undetectable in SAGM blood. Spontaneous histamine release increased in a time-dependent manner from a median of 6.7 (range 2.2-17.4) nmol/l at the time of storage to 175.0 (range 33...

HISTAMINE IN CANNED SARDINES HISTAMINA EM CONSERVAS DE SARDINHA

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Fancislene Bernardes Tebalti do Carmo

2010-04-01

Full Text Available In this study, the presence of histamine in 122 samples of canned sardines produced with three different species by three industries located in the municipalities of Sao Goncalo and Niteroi was evaluated. The samples were divided into five lots with copies of sardines from Venezuela (Sardinella aurita, Morocco (S. pilchardus and Brazil (S. brasiliensis. The initial quality of raw material was evaluated by sensorial parameters and by the histamine level using a semi-quantitative method of thin-layer chromatography. The results of the samples from Venezuela and Morocco showed values below 5 mg/100g, and the national samples showed values similar or greater than 10 mg/100g. It follows that there is need for greater control and monitoring of temperature from capture to processing, to guarantee good quality to the final product, and to avoid risk of poisoning to the consumer.

KEY WORDS: Canned fish, histamine, quality, sardines.

O presente estudo avaliou a presença de histamina em 122 amostras de sardinha em conserva, produzidas com três diferentes espécies, por três indústrias, localizadas nos municípios de São Gonçalo e Niterói. As amostras foram divididas em cinco lotes com exemplares de sardinhas provenientes da Venezuela (Sardinella aurita, Marrocos (S. pilchardus e do Brasil (S. brasiliensis. Avaliou-se a qualidade inicial da matéria-prima por meio de parâmetros sensoriais e pelo teor de histamina utilizando-se o método de cromatografia em camada delgada. As amostras oriundas da Venezuela e Marrocos apresentaram valores abaixo de 5 mg/100 g e as nacionais, valores semelhantes ou superiores a 10 mg/100g. Conclui-se que há necessidade de um maior controle e monitorização da temperatura da sardinha desde a captura até o processamento, para que o produto final apresente boa qualidade e não represente perigo de intoxicação ao consumidor.

PALAVRAS-CHAVES: Conserva, histamina, qualidade, sardinha.

The metabolism of histamine in the Drosophila optic lobe involves an ommatidial pathway: β-alanine recycles through the retina

Science.gov (United States)

Borycz, Janusz; Borycz, Jolanta A.; Edwards, Tara N.; Boulianne, Gabrielle L.; Meinertzhagen, Ian A.

2012-01-01

SUMMARY Flies recycle the photoreceptor neurotransmitter histamine by conjugating it to β-alanine to form β-alanyl-histamine (carcinine). The conjugation is regulated by Ebony, while Tan hydrolyses carcinine, releasing histamine and β-alanine. In Drosophila, β-alanine synthesis occurs either from uracil or from the decarboxylation of aspartate but detailed roles for the enzymes responsible remain unclear. Immunohistochemically detected β-alanine is present throughout the fly’s entire brain, and is enhanced in the retina especially in the pseudocone, pigment and photoreceptor cells of the ommatidia. HPLC determinations reveal 10.7 ng of β-alanine in the wild-type head, roughly five times more than histamine. When wild-type flies drink uracil their head β-alanine increases more than after drinking l-aspartic acid, indicating the effectiveness of the uracil pathway. Mutants of black, which lack aspartate decarboxylase, cannot synthesize β-alanine from l-aspartate but can still synthesize it efficiently from uracil. Our findings demonstrate a novel function for pigment cells, which not only screen ommatidia from stray light but also store and transport β-alanine and carcinine. This role is consistent with a β-alanine-dependent histamine recycling pathway occurring not only in the photoreceptor terminals in the lamina neuropile, where carcinine occurs in marginal glia, but vertically via a long pathway that involves the retina. The lamina’s marginal glia are also a hub involved in the storage and/or disposal of carcinine and β-alanine. PMID:22442379

The mast cell stabilizer sodium cromoglycate reduces histamine release and status epilepticus-induced neuronal damage in the rat hippocampus.

Science.gov (United States)

Valle-Dorado, María Guadalupe; Santana-Gómez, César Emmanuel; Orozco-Suárez, Sandra Adela; Rocha, Luisa

2015-05-01

Experiments were designed to evaluate changes in the histamine release, mast cell number and neuronal damage in hippocampus induced by status epilepticus. We also evaluated if sodium cromoglycate, a stabilizer of mast cells with a possible stabilizing effect on the membrane of neurons, was able to prevent the release of histamine, γ-aminobutyric acid (GABA) and glutamate during the status epilepticus. During microdialysis experiments, rats were treated with saline (SS-SE) or sodium cromoglycate (CG-SE) and 30 min later received the administration of pilocarpine to induce status epilepticus. Twenty-four hours after the status epilepticus, the brains were used to determine the neuronal damage and the number of mast cells in hippocampus. During the status epilepticus, SS-SE group showed an enhanced release of histamine (138.5%, p = 0.005), GABA (331 ± 91%, p ≤ 0.001) and glutamate (467%, p ≤ 0.001), even after diazepam administration. One day after the status epilepticus, SS-SE group demonstrated increased number of mast cells in Stratum pyramidale of CA1 (88%, p status epilepticus (p = 0.048), absence of wet-dog shakes, reduced histamine (but not GABA and glutamate) release, lower number of mast cells (p = 0.008) and reduced neuronal damage in hippocampus. Our data revealed that histamine, possibly from mast cells, is released in hippocampus during the status epilepticus. This effect may be involved in the subsequent neuronal damage and is diminished with sodium cromoglycate pretreatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Interference of WEB 2086 and BN 52021 with Paf-induced effects on guinea-pig trachea.

OpenAIRE

Brunelleschi, S.; Renzi, D.; Ledda, F.; Giotti, A.; Fantozzi, R.; Brink, C.; Benveniste, J.

1989-01-01

1. The thienotriazolodiazepine WEB 2086 and the gingkolide BN52021 have been evaluated as antagonists of Paf-acether (Paf) by studying their effects on Paf-induced relaxation and Paf-induced prostaglandin E2 (PGE2) production in histamine-contracted guinea-pig tracheal preparations. 2. Relaxation induced by Paf 4 microM in histamine-contracted guinea-pig tracheal preparations was 39.67 +/- 3.5% (n = 30). At the same concentration, Paf significantly increased PGE2 production from histamine-con...

Flavonoids inhibit histamine release and expression of proinflammatory cytokines in mast cells.

Science.gov (United States)

Park, Hyo-Hyun; Lee, Soyoung; Son, Hee-Young; Park, Seung-Bin; Kim, Mi-Sun; Choi, Eun-Ju; Singh, Thoudam S K; Ha, Jeoung-Hee; Lee, Maan-Gee; Kim, Jung-Eun; Hyun, Myung Chul; Kwon, Taeg Kyu; Kim, Yeo Hyang; Kim, Sang-Hyun

2008-10-01

Mast cells participate in allergy and inflammation by secreting inflammatory mediators such as histamine and proinflammatory cytokines. Flavonoids are naturally occurring molecules with antioxidant, cytoprotective, and antiinflammatory actions. However, effect of flavonoids on the release of histamine and proinflammatory mediator, and their comparative mechanism of action in mast cells were not well defined. Here, we compared the effect of six flavonoids (astragalin, fisetin, kaempferol, myricetin, quercetin, and rutin) on the mast cell-mediated allergic inflammation. Fisetin, kaempferol, myricetin, quercetin, and rutin inhibited IgE or phorbol-12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-mediated histamine release in RBL-2H3 cells. These five flavonoids also inhibited elevation of intracellular calcium. Gene expressions and secretion of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, and IL-8 were assessed in PMACI-stimulated human mast cells (HMC-1). Fisetin, quercetin, and rutin decreased gene expression and production of all the proinflammatory cytokines after PMACI stimulation. Myricetin attenuated TNF-alpha and IL-6 but not IL-1beta and IL-8. Fisetin, myricetin, and rutin suppressed activation of NF-kappaB indicated by inhibition of nuclear translocation of NF-kappaB, NF-kappaB/DNA binding, and NF-kappaB-dependent gene reporter assay. The pharmacological actions of these flavonoids suggest their potential activity for treatment of allergic inflammatory diseases through the down-regulation of mast cell activation.

The Effects of Electrical Stimuli on Calcium Change and Histamine Release in Rat Basophilic Leukemia Mast Cells

Science.gov (United States)

Zhu, Dan; Wu, Zu-Hui; Chen, Ji-Yao; Zhou, Lu-Wei

2013-06-01

We apply electric fields at different frequencies of 0.1, 1, 10 and 100 kHz to the rat basophilic leukemia (RBL) mast cells in calcium-containing or calcium-free buffers. The stimuli cause changes of the intracellular calcium ion concentration [Ca2+]i as well as the histamine. The [Ca2+]i increases when the frequency of the external electric field increases from 100 Hz to 10 kHz, and then decreases when the frequency further increases from 10 kHz to 100 kHz, showing a peak at 100 kHz. A similar frequency dependence of the histamine release is also found. The [Ca2+]i and the histamine releases at 100 Hz are about the same as the values of the control group with no electrical stimulation. The ruthenium red (RR), an inhibitor to the TRPV (transient receptor potential (TRP) family V) channels across the cell membrane, is used in the experiment to check whether the electric field stimuli act on the TRPV channels. Under an electric field of 10 kHz, the [Ca2+]i in a calcium-concentration buffer is about 3.5 times as much as that of the control group with no electric stimulation, while the [Ca2+]i in a calcium-free buffer is only about 2.2 times. Similar behavior is also found for the histamine release. RR blockage effect on the [Ca2+]i decrease is statistically significant (~75%) when mast cells in the buffer with calcium are stimulated with a 10 kHz electric field in comparison with the result without the RR treatment. This proves that TRPVs are the channels that calcium ions inflow through from the extracellular environment under electrical stimuli. Under this condition, the histamine is also released following a similar way. We suggest that, as far as an electric stimulation is concerned, an application of ac electric field of 10 kHz is better than other frequencies to open TRPV channels in mast cells, and this would cause a significant calcium influx resulting in a significant histamine release, which could be one of the mechanisms for electric therapy.

Significant histamine formation in tuna ( Thunnus albacares ) at 2 degrees C - effect of vacuum- and modified atmosphere-packaging on psychrotolerant bacteria

DEFF Research Database (Denmark)

Emborg, Jette; Laursen, B. G.; Dalgaard, Paw

2005-01-01

Occurrence and importance of psychrotolerant histamine producing bacteria in chilled fresh tuna were demonstrated in the present study. The objective was to evaluate microbial formation of histamine and biogenic amines in chilled fresh tuna from the Indian Ocean and stored either vacuum-packed (VP...

On the influence of dexamethason-21-iso-nicotinate on histamine blood level in horses with reference to the facultative occurrence of laminitis

International Nuclear Information System (INIS)

Rautschka, R.

1987-10-01

In some cases laminitis may result as a consequence of corticoid therapy in horses. It was the aim of this investigation to prove, if there is a connection between therapeutic doses of a corticoid (dexamethasone-21-iso-nicotinate) and the liberation of histamine into the equine plasma. 40 veterinarians reported 23 cases of laminitis after treating the horses with various corticoids. To determine histamine levels in equine plasma, a method used in human medicine (Faraj, 1984) was adapted accordingly. The principle of this method consists of enzymatic coupling of a tritium-labelled methyl group to the histamine contained in plasma. From the investigation the conclusion could be drawn, that it was not possible to induce liberation of histamine into equine plasma by therapeutic doses of dexamethasone-21-iso-nicotinate. Finally, plasma levels of three horses, suffering from chronical obstructive pulmonary disease (COPD) treated therapeutically with dexamethasone-21-iso-nicotinate, were determined. Conclusively a connection between the i.m. application of dexamethasone-21-iso-nicotinate and an inducement of histamine liberation into equine plasma could not be proven. 226 refs., 11 figs., 12 tabs. (G.Q.)

Effects of dimethylsulfoxide (DMSO), nocodazole, and taxol on mast cell histamine secretion

DEFF Research Database (Denmark)

Nielsen, E H; Johansen, Torben

1986-01-01

Nocodazole depolymerized microtubules and increased the number of microfilaments, and dimethylsulfoxide increased the number of microfilaments. Both drugs inhibited compound 48/80-induced histamine release from rat mast cells. Taxol, which increased the number of microtubules, had no effect on hi...

The role of histamine degradation gene polymorphisms in moderating the effects of food additives on children's ADHD symptoms.

Science.gov (United States)

Stevenson, Jim; Sonuga-Barke, Edmund; McCann, Donna; Grimshaw, Kate; Parker, Karen M; Rose-Zerilli, Matthew J; Holloway, John W; Warner, John O

2010-09-01

Food additives can exacerbate ADHD symptoms and cause non-immunoglobulin E-dependent histamine release from circulating basophils. However, children vary in the extent to which their ADHD symptoms are exacerbated by the ingestion of food additives. The authors hypothesized that genetic polymorphisms affecting histamine degradation would explain the diversity of responses to additives. In a double-blind, placebo-controlled crossover trial, challenges involving two food color additive and sodium benzoate (preservative) mixtures in a fruit drink were administered to a general community sample of 3-year-old children (N = 153) and 8/9-year-old children (N = 144). An aggregate ADHD symptom measure (based on teacher and parent blind ratings of behavior, blind direct observation of behavior in the classroom, and--for 8/9-year-old children only--a computerized measure of attention) was the main outcome variable. The adverse effect of food additives on ADHD symptoms was moderated by histamine degradation gene polymorphisms HNMT T939C and HNMT Thr105Ile in 3- and 8/9-year-old children and by a DAT1 polymorphism (short versus long) in 8/9-year-old children only. There was no evidence that polymorphisms in catecholamine genes COMT Val108Met, ADRA2A C1291G, and DRD4-rs7403703 moderated the effect on ADHD symptoms. Histamine may mediate the effects of food additives on ADHD symptoms, and variations in genes influencing the action of histamine may explain the inconsistency between previous studies. Genes influencing a range of neurotransmitter systems and their interplay with environmental factors, such as diet, need to be examined to understand genetic influences on ADHD symptoms.

Histaminergic activity in a rodent model of Parkinson's disease.

Science.gov (United States)

Nowak, Przemysław; Noras, Lukasz; Jochem, Jerzy; Szkilnik, Ryszard; Brus, Halina; Körossy, Eva; Drab, Jacek; Kostrzewa, Richard M; Brus, Ryszard

2009-04-01

Rats lesioned shortly after birth with 6-OHDA have been proposed to be a near-ideal model of severe Parkinson's disease, because of non-lethality of the procedure, near-total destruction of nigrostriatal dopaminergic fibers, and near-total dopamine (DA) denervation of striatum. There are scarce data that in Parkinson's disease, activity of the central histaminergic system is increased. Therefore, the aim of this study was to determine histamine content in the brain and the effect of histamine receptor antagonists on behavior of adult rats. At 3 days after birth, Wistar rats were pretreated with desipramine (20.0 mg/kg ip) 1 h before bilateral icv administration of the catecholaminergic neurotoxin 6-OHDA (67 microg base, on each side) or saline-ascorbic acid (0.1%) vehicle (control). At 8 weeks levels of DA and its metabolites L: -3,4-dihydroxyphenylalanine (DOPAC) and homovanillic acid (HVA) were estimated in the striatum and frontal cortex by HPCL/ED technique. In the hypothalamus, hippocampus, frontal cortex, and medulla oblongata, the level of histamine was analyzed by immunoenzymatic method. Behavioral observations (locomotion, exploratory-, oral-, and stereotyped-activity) were additionally made on control and 6-OHDA neonatally lesioned rats. Effects of DA receptor agonists (SKF 38393, apomorphine) and histamine receptor antagonists (e.g., S(+)chlorpheniramine, H(1); cimetidine, H(2); thioperamide, H(3) agonist) were determined. We confirmed that 6-OHDA significantly reduced contents of DA and its metabolites in the brain in adulthood. Histamine content was significantly increased in the hypothalamus, hipocampus, and medulla oblongata. Moreover, in 6-OHDA-lesioned rats behavioral response was altered mainly by thioperamide (H(3) antagonist). These findings indicate that histamine and the central histaminergic system are altered in the brain of rats lesioned to model Parkinson's disease, and that histaminergic neurons exert a modulating role in Parkinsonian 6

Histamine H2 Receptor-Mediated Suppression of Intestinal Inflammation by Probiotic Lactobacillus reuteri.

Science.gov (United States)

Gao, Chunxu; Major, Angela; Rendon, David; Lugo, Monica; Jackson, Vanessa; Shi, Zhongcheng; Mori-Akiyama, Yuko; Versalovic, James

2015-12-15

Probiotics and commensal intestinal microbes suppress mammalian cytokine production and intestinal inflammation in various experimental model systems. Limited information exists regarding potential mechanisms of probiotic-mediated immunomodulation in vivo. In this report, we demonstrate that specific probiotic strains of Lactobacillus reuteri suppress intestinal inflammation in a trinitrobenzene sulfonic acid (TNBS)-induced mouse colitis model. Only strains that possess the hdc gene cluster, including the histidine decarboxylase and histidine-histamine antiporter genes, can suppress colitis and mucosal cytokine (interleukin-6 [IL-6] and IL-1β in the colon) gene expression. Suppression of acute colitis in mice was documented by diminished weight loss, colonic injury, serum amyloid A (SAA) protein concentrations, and reduced uptake of [(18)F]fluorodeoxyglucose ([(18)F]FDG) in the colon by positron emission tomography (PET). The ability of probiotic L. reuteri to suppress colitis depends on the presence of a bacterial histidine decarboxylase gene(s) in the intestinal microbiome, consumption of a histidine-containing diet, and signaling via the histamine H2 receptor (H2R). Collectively, luminal conversion of l-histidine to histamine by hdc(+) L. reuteri activates H2R, and H2R signaling results in suppression of acute inflammation within the mouse colon. Probiotics are microorganisms that when administered in adequate amounts confer beneficial effects on the host. Supplementation with probiotic strains was shown to suppress intestinal inflammation in patients with inflammatory bowel disease and in rodent colitis models. However, the mechanisms of probiosis are not clear. Our current studies suggest that supplementation with hdc(+) L. reuteri, which can convert l-histidine to histamine in the gut, resulted in suppression of colonic inflammation. These findings link luminal conversion of dietary components (amino acid metabolism) by gut microbes and probiotic

Adenosine: a putative mediator of bronchoconstriction in asthma

Energy Technology Data Exchange (ETDEWEB)

Mann, J.S.

1987-01-01

The protective effect of a muscarinic cholinergic antagonists, ipratropium bromide (IB) from inhaled adenosine- and methacholine-induced bronchoconstriction in asthma was studied. Inhaled IB protected from methacholine- but not adenosine-induced bronchoconstriction. Parasympathetically mediated bronchoconstriction is therefore unlikely to account for adenosine's airway effect in asthma. The capacity of theophylline, a bronchodilator and a competitive antagonist of adenosine at its cell surface receptors, to protect asthmatic subjects from adenosine- and histamine-induced bronchoconstriction was determined. Asthmatic airways are infiltrated with inflammatory cells. Human leucocytes prelabeled with (/sup 3/H)-adenine when activated with the calcium ionophore A23187 released labelled hypoxanthine, inosine and adenosine which was associated with a dose-related release of histamine. The chemotactic peptide f-MLP while inducing histamine release had an inconstant effect on release of label. In four of five experiments f-MLP produced a transient early increase in label release but in the remaining experiment no significant release was observed. Anti-human IgE failed to induce significant label release despite releasing histamine. Activated leucocytes are therefore a potential source of adenosine in asthma.

Effect of ozone and histamine on airway permeability to horseradish peroxidase in guinea pigs

International Nuclear Information System (INIS)

Miller, P.D.; Gordon, T.; Warnick, M.; Amdur, M.O.

1986-01-01

Airway permeability was studied in groups of male guinea pigs at 2, 8, and 24 h after a 1-h exposure to 1 ppm ozone or at 2 h after a 1-h exposure to filtered air (control). Intratracheal administration of 2 mg horseradish peroxidase (HRP) was followed by blood sampling at 5-min intervals up to 30 min. The rate of appearance of HRP in plasma was significantly higher at 2 and 8 h after ozone exposure than that found in animals examined 2 h after air exposure or 24 h after ozone exposure. A dose of 0.12 mg/kg of subcutaneous histamine given after the 15 min blood sample significantly increased the already elevated permeability seen at 2 h post ozone, but had no effect on animals exposed to filtered air 2 h earlier or to ozone 24 h earlier. No difference was seen in the amount of subcutaneous radiolabeled histamine in the lungs of animals exposed 2 h earlier either to air or to ozone. These data indicate that a short-term exposure to ozone produced a reversible increase in respiratory epithelial permeability to HRP in guinea pigs. The potentiation of this increased permeability by histamine may be another manifestation of ozone-induced hyperreactivity

Lactobacillus reuteri-specific immunoregulatory gene rsiR modulates histamine production and immunomodulation by Lactobacillus reuteri.

Science.gov (United States)

Hemarajata, P; Gao, C; Pflughoeft, K J; Thomas, C M; Saulnier, D M; Spinler, J K; Versalovic, J

2013-12-01

Human microbiome-derived strains of Lactobacillus reuteri potently suppress proinflammatory cytokines like human tumor necrosis factor (TNF) by converting the amino acid l-histidine to the biogenic amine histamine. Histamine suppresses mitogen-activated protein (MAP) kinase activation and cytokine production by signaling via histamine receptor type 2 (H2) on myeloid cells. Investigations of the gene expression profiles of immunomodulatory L. reuteri ATCC PTA 6475 highlighted numerous genes that were highly expressed during the stationary phase of growth, when TNF suppression is most potent. One such gene was found to be a regulator of genes involved in histidine-histamine metabolism by this probiotic species. During the course of these studies, this gene was renamed the Lactobacillus reuteri-specific immunoregulatory (rsiR) gene. The rsiR gene is essential for human TNF suppression by L. reuteri and expression of the histidine decarboxylase (hdc) gene cluster on the L. reuteri chromosome. Inactivation of rsiR resulted in diminished TNF suppression in vitro and reduced anti-inflammatory effects in vivo in a trinitrobenzene sulfonic acid (TNBS)-induced mouse model of acute colitis. A L. reuteri strain lacking an intact rsiR gene was unable to suppress colitis and resulted in greater concentrations of serum amyloid A (SAA) in the bloodstream of affected animals. The PhdcAB promoter region targeted by rsiR was defined by reporter gene experiments. These studies support the presence of a regulatory gene, rsiR, which modulates the expression of a gene cluster known to mediate immunoregulation by probiotics at the transcriptional level. These findings may point the way toward new strategies for controlling gene expression in probiotics by dietary interventions or microbiome manipulation.

Histamine release positive test associates with disease remission in chronic spontaneous urticaria

DEFF Research Database (Denmark)

Berti, A; Yacoub, M R; Skov, Per Stahl

2017-01-01

the correlations between HR test results and demographic features, quality of life, disease activity, clinical course, and autologous serum and plasma skin tests (ASST and APST). Results. All patients with positive HR test (9/9, 100%) had a more severe disease activity at onset (urticaria activity score, UAS > 2......Summary: Background. Histamine release (HR) test has previously been shown to predict the presence of endogenous histamine-releasing factors in chronic spontaneous urticaria (CSU). Objectives and methods. Twenty CSU patients unresponsive to antihistamine treatment were enrolled in order to evaluate...... with a positive HR test had a significant reduction of disease activity (p = 0.003) whereas patients with a negative HR test did not (p > 0.05), leading to disease remission and antihistamine treatment withdrawal in 67% (6/9) of positive HR test patients versus 18% (2/11) of negative HR test patients (p = 0...

Histamine-dependent behavioral response to methamphetamine in 12-month-old male mice

Science.gov (United States)

Acevedo, Summer F.; Raber, Jacob

2011-01-01

Methamphetamine (MA) use is a growing problem across the United States. Effects of MA include hyperactivity and increased anxiety. Using a mouse model system, we examined behavioral performance in the open field and elevated zero maze and shock-startle response of 12-month-old wild-type mice injected with MA once (1mg/kg) 30 min prior to behavioral testing. MA treatment resulted in behavioral sensitization in the open field, consistent with studies in younger mice. There was an increased activity in the elevated zero maze and an increased shock-startle response 30 and 60 min post-injection. Since histamine mediates some effects of MA in the brain, we assessed whether 12-month-old mice lacking histidine decarboxylase (Hdc−/−), the enzyme required to synthesize histamine, respond differently to MA than wild-type (Hdc+/+) mice. Compared to saline treatment, acute and repeated MA administration increased activity in the open field and measures of anxiety, though more so in Hdc−/− than Hdc+/+ mice. In the elevated zero maze, opposite effects of MA on activity and measures of anxiety were seen in Hdc+/+ mice. In contrast, MA similarly increased the shock-startle response in Hdc−/− and Hdc+/+ mice, compared to saline-treated genotype-matched mice. These results are similar to those in younger mice suggesting that the effects are not age-dependent. Overall, single or repeated MA treatment causes histamine-dependent changes in 12-month-old mice in the open field and elevated zero-maze, but not in the shock-startle response. PMID:21466792

Ciproxifan, a histamine H{sub 3} receptor antagonist and inverse agonist, presynaptically inhibits glutamate release in rat hippocampus

Energy Technology Data Exchange (ETDEWEB)

Lu, Cheng-Wei; Lin, Tzu-Yu [Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei City 22060, Taiwan (China); Department of Mechanical Engineering, Yuan Ze University, Taoyuan 320, Taiwan (China); Chang, Chia-Ying [Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei City 22060, Taiwan (China); Department of Chemistry, Fu Jen Catholic University, No. 510, Chung-Cheng Road, Hsin-Chuang District, New Taipei City 24205, Taiwan (China); Huang, Shu-Kuei [Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei City 22060, Taiwan (China); Wang, Su-Jane, E-mail: med0003@mail.fju.edu.tw [School of Medicine, Fu Jen Catholic University, No. 510, Chung-Cheng Rd., Hsin-Chuang, New Taipei 24205, Taiwan (China); Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan City, Taiwan (China)

2017-03-15

Ciproxifan is an H{sub 3} receptor antagonist and inverse agonist with antipsychotic effects in several preclinical models; its effect on glutamate release has been investigated in the rat hippocampus. In a synaptosomal preparation, ciproxifan reduced 4-aminopyridine (4-AP)-evoked Ca{sup 2+}-dependent glutamate release and cytosolic Ca{sup 2+} concentration elevation but did not affect the membrane potential. The inhibitory effect of ciproxifan on 4-AP-evoked glutamate release was prevented by the Gi/Go-protein inhibitor pertussis toxin and Ca{sub v}2.2 (N-type) and Ca{sub v}2.1 (P/Q-type) channel blocker ω-conotoxin MVIIC, but was not affected by the intracellular Ca{sup 2+}-release inhibitors dantrolene and CGP37157. Furthermore, the phospholipase A{sub 2} (PLA{sub 2}) inhibitor OBAA, prostaglandin E{sub 2} (PGE{sub 2}), PGE2 subtype 2 (EP{sub 2}) receptor antagonist PF04418948, and extracellular signal-regulated kinase (ERK) inhibitor FR180204 eliminated the inhibitory effect of ciproxifan on glutamate release. Ciproxifan reduced the 4-AP-evoked phosphorylation of ERK and synapsin I, a presynaptic target of ERK. The ciproxifan-mediated inhibition of glutamate release was prevented in synaptosomes from synapsin I-deficient mice. Moreover, ciproxifan reduced the frequency of miniature excitatory postsynaptic currents without affecting their amplitude in hippocampal slices. Our data suggest that ciproxifan, acting through the blockade of Gi/Go protein-coupled H{sub 3} receptors present on hippocampal nerve terminals, reduces voltage-dependent Ca{sup 2+} entry by diminishing PLA{sub 2}/PGE{sub 2}/EP{sub 2} receptor pathway, which subsequently suppresses the ERK/synapsin I cascade to decrease the evoked glutamate release. - Highlights: • Ciproxifan presynaptically reduces glutamate release in the hippocampus in vitro. • Decrease in voltage-dependent Ca{sup 2+} influx is involved. • A role for the PLA{sub 2}/PGE{sub 2}/EP{sub 2} pathway in the action of

Aortic endothelial and smooth muscle histamine metabolism. Relationship to aortic 125I-albumin accumulation in experimental diabetes

International Nuclear Information System (INIS)

Hollis, T.M.; Gallik, S.G.; Orlidge, A.; Yost, J.C.

1983-01-01

We studied rat aortic endothelial and smooth muscle cell de novo histamine synthesis mediated by histidine decarboxylase (HD) and the effects of its inhibition by alpha-hydrazinohistidine on the intracellular histamine content and intraaortic albumin accumulation in streptozotocin-induced diabetes. Diabetes was induced by a single jugular vein injection of streptozotocin (60 mg/kg, pH 4.5, ether anesthesia), with animals held 4 weeks following the overt manifestation of diabetes. Additional diabetic and nondiabetic rats received alpha-hydrazinohistidine (25 mg/kg, i.p. every 12 hours) during the last week; this had no effect on the severity of diabetes in any animal receiving streptozotocin. Data indicate that the aortic endothelial (EC) HD activity was increased more than 130% in the untreated diabetic group but was similar to control values in the diabetic group receiving alpha-hydrazinohistidine; similarily, the EC histamine content from diabetic aortas increased 127% over control values, but in EC from diabetic animals receiving alpha-hydrazinohistidine it was comparable to control values. Similar trends were observed for the subjacent aortic smooth muscle. In untreated diabetic animals the aortic 125I-albumin mass transfer rate was increased 60% over control values, while in diabetic animals receiving alpha-hydrazinohistidine the 125I-albumin mass transfer rate was essentially identical to controls. These data indicate that in streptozotocin diabetes there is an expansion of the inducible aortic histamine pool, and that this expansion is intimately related to the increased aortic albumin accumulation

The effects of thermal stimuli on intracellular calcium change and histamine releases in rat basophilic leukemia mast cells

Science.gov (United States)

Wu, Zu-Hui; Zhu, Dan; Chen, Ji-Yao; Zhou, Lu-Wei

2012-05-01

The effects of thermal stimuli on rat basophilic leukemia mast cells were studied. The cells in calcium-contained or calcium-free buffers were thermally stimulated in the temperature range of 25-60 °C. The corresponding calcium ion concentration in cells [Ca2+]i as well as the released histamine from cells was measured with fluorescence staining methods. The ruthenium red (RR), a block of membrane calcium channels (transient receptor potential family V (TRPV)), was used in experiments. Under the stimulus of 25-50 °C, no significant difference on [Ca2+]i was found between these three groups of the cells in calcium-contained buffer without or with RR and cells in calcium-free saline, indicating that the increased calcium in cytosol did not result from the extracellular buffer but came from the intracellular calcium stores. The [Ca2+]i continuously increased under the temperature of 50-60 °C, but the RR and calcium-free saline can obviously diminish the [Ca2+]i increase at these high temperatures, reflecting that the opening of the TRPV2 channels leads to a calcium influx resulting in the [Ca2+]i increment. The histamine release also became significant in these cases. Since the released histamine is a well-known mediator for the microcirculation promotion, the histamine release from mast cells could be one of the mechanisms of thermal therapy.

Effects of oral cetirizine, a selective H1 antagonist, on allergen- and exercise-induced bronchoconstriction in subjects with asthma.

LENUS (Irish Health Repository)

Gong, H

1990-03-01

The protective efficacy of oral cetirizine, a selective and potent H1-receptor antagonist, against the immediate bronchoconstrictive response to allergen inhalation and exercise challenge was evaluated in 16 subjects with stable, predominantly mild asthma. The subjects underwent double-blind, crossover pretreatments in randomized order in two separate protocols with (1) three daily oral doses of 20 mg of cetirizine and placebo, followed by allergen inhalation, and (2) single oral doses of cetirizine (5, 10, and 20 mg), albuterol (4 mg), and placebo, followed by exercise with cold-air inhalation. Cetirizine failed to decrease bronchial sensitivity to inhaled allergen in eight of 10 subjects. Neither cetirizine nor albuterol uniformly inhibited exercise-induced bronchoconstriction. Serum concentrations of cetirizine were consistent with systemic H1-blocking activity. Modest bronchodilation occurred after administration of cetirizine and albuterol before exercise but not after the third dose of cetirizine in the allergen protocol. One subject developed moderate drowsiness during multiple dosing with cetirizine. Thus, cetirizine, in the doses studied, is not uniformly effective in preventing allergen- or exercise-induced bronchoconstriction. Histamine is one of many mediators participating in immediate asthmatic responses, and selective H1 antagonists do not completely block these airway events. However, cetirizine may still clinically benefit some patients with asthma, such as patients with allergic rhinitis or urticaria.

Response localization of the pharmacological agents histamine and salbutamol along the respiratory system by forced oscillations in asthmatic subjects.

Science.gov (United States)

Wouters, E F; Polko, A H; Visser, B F

1989-01-01

The bronchodilating effect of 1 mg and 0.4 mg salbutamol on the impedance of the respiratory system was studied in 25 asthmatic subjects after histamine-induced bronchoconstriction. Histamine caused an increase of respiratory resistance (Rrs) at lower frequencies and a frequency dependence of Rrs. Respiratory reactance (Xrs) decreased at all frequencies after histamine challenge. These changes can be explained by peripheral airway obstruction. Impedance measurements performed 5 min after inhalation of 1 mg and 0.4 mg salbutamol showed a decrease of Rrs values at lower frequencies, a disappearance of the frequency dependence of Rrs, and a significant increase of Xrs values. No significant differences in absolute changes of Rrs and Xrs are observed between the salbutamol regimens. These changes after inhalation of salbutamol can be explained by supposing a predominant action on the peripheral airways.

Effects of inspiratory resistance, inhaled beta-agonists and histamine on canine tracheal blood flow

International Nuclear Information System (INIS)

Kelly, W.T.; Baile, E.M.; Brancatisano, A.; Pare, P.D.; Engel, L.A.

1992-01-01

Tracheobronchial blood flow is potentially important in asthma as it could either influence the clearance of mediators form the airways, thus affecting the duration and severity of bronchoispasm, or enhance oedema formation with a resultant increase in airflow obstruction. In anaesthetized dogs, spontaneously breathing via a tracheostomy, we investigated the effects of three interventions which are relevant to acute asthma attacks and could potentially influence blood flow and its distribution to the mucosa and remaining tissues of the trachea: 1) increased negative intrathoracic pressure swings (-25±1 cmH 2 O) induced by an inspiratory resistance; 2) variable inhaled doses of a beta-adrenoceptor-agonist (terbutaline); and 3) aerosolized histamine sufficient to produce a threefold increase in pulmonary resistance. Microspheres labelled with different radioisotopes were used to measure blood flow. Resistive breathing did not influence tracheobronchial blood flow. Following a large dose of terbutaline, mucosal blood flow (Qmb) increased by 50%. After inhaled histamine, Qmb reached 265% of the baseline value. We conclude that, whereas increased negative pressure swings do not influence tracheobronchial blood flow or its distribution, inhalation of aerosolized terbutaline, corresponding to a conventionally nebulized dose, increases mucosal blood flow. Our results also confirm that inhaled histamine, in a dose sufficient to produce moderate bronchoconstriction, increases tracheal mucosal blood flow in the area of deposition. (au)

Effects of inspiratory resistance, inhaled beta-agonists and histamine on canine tracheal blood flow

Energy Technology Data Exchange (ETDEWEB)

Kelly, W.T.; Baile, E.M.; Brancatisano, A.; Pare, P.D.; Engel, L.A. (Dept. of Respiratory Medicine, Westmead Hospital, Westmead, NSW (Australia))

1992-01-01

Tracheobronchial blood flow is potentially important in asthma as it could either influence the clearance of mediators form the airways, thus affecting the duration and severity of bronchoispasm, or enhance oedema formation with a resultant increase in airflow obstruction. In anaesthetized dogs, spontaneously breathing via a tracheostomy, we investigated the effects of three interventions which are relevant to acute asthma attacks and could potentially influence blood flow and its distribution to the mucosa and remaining tissues of the trachea: (1) increased negative intrathoracic pressure swings (-25[+-]1 cmH[sub 2]O) induced by an inspiratory resistance; (2) variable inhaled doses of a beta-adrenoceptor-agonist (terbutaline); and (3) aerosolized histamine sufficient to produce a threefold increase in pulmonary resistance. Microspheres labelled with different radioisotopes were used to measure blood flow. Resistive breathing did not influence tracheobronchial blood flow. Following a large dose of terbutaline, mucosal blood flow (Qmb) increased by 50%. After inhaled histamine, Qmb reached 265% of the baseline value. We conclude that, whereas increased negative pressure swings do not influence tracheobronchial blood flow or its distribution, inhalation of aerosolized terbutaline, corresponding to a conventionally nebulized dose, increases mucosal blood flow. Our results also confirm that inhaled histamine, in a dose sufficient to produce moderate bronchoconstriction, increases tracheal mucosal blood flow in the area of deposition. (au).

[Shikimic acid inhibits the degranulation and histamine release in RBL-2H3 cells].

Science.gov (United States)

Chen, Xianyong; Zheng, Qianqian; Liu, Wei; Yu, Lingling; Wang, Jinling; Li, Shigang

2017-05-01

Objective To study the effects of shikimic acid on the proliferation of rat RBL-2H3 cells and the degranulation of the cells induced by C48/80 and its mechanism. Methods MTT assay was performed to measure the proliferation of RBL-2H3 cells treated with 3, 10, 30 μg/mL shikimic acid. Toluidine blue staining was used to observe the degranulation of RBL-2H3 cells. The release of β-hexosaminidase from RBL-2H3 cells treated with 0, 12.5, 25, 50, 80, 100 μg/mL C48/80 was determined by substrate assay. ELISA was used to detect the histamine content in the supernatant of each treated group. Results Shikimic acid at 3, 10, 300 μg/mL had no obvious inhibitory effect on the proliferation of RBL-2H3 cells. There was a dose-effect relationship between the degranulation of RBL-2H3 cells and C48/80 concentration. Shikimic acid inhibited the degranulation of RBL-2H3 cells compared with the positive control group, the β-hexosaminidase release rate and histamine release were significantly reduced in RBL-2H3 cells treated with shikimic acid and C48/80. Conclusion Shikimic acid can inhibit the degranulation of RBL-2H3 cells and reduce histamine release.

Tuneable surface enhanced Raman spectroscopy hyphenated to chemically derivatized thin-layer chromatography plates for screening histamine in fish.

Science.gov (United States)

Xie, Zhengjun; Wang, Yang; Chen, Yisheng; Xu, Xueming; Jin, Zhengyu; Ding, Yunlian; Yang, Na; Wu, Fengfeng

2017-09-01

Reliable screening of histamine in fish was of urgent importance for food safety. This work presented a highly selective surface enhanced Raman spectroscopy (SERS) method mediated by thin-layer chromatography (TLC), which was tailored for identification and quantitation of histamine. Following separation and derivatization with fluram, plates were assayed with SERS, jointly using silver nanoparticle and NaCl. The latter dramatically suppressed the masking effect caused by excessive fluram throughout the plate, thus offering clear baseline and intensive Raman fingerprints specific to the analyte. Under optimized conditions, the usability of this method was validated by identifying the structural fingerprints of both targeted and unknown compounds in fish samples. Meanwhile, the quantitative results of this method agreed with those by an HPLC method officially suggested by EU for histamine determination. Showing remarkable cost-efficiency and user-friendliness, this facile TLC-SERS method was indeed screening-oriented and may be more attractive to controlling laboratories of limited resource. Copyright © 2017 Elsevier Ltd. All rights reserved.

Communication between mast cells and rat submucosal neurons.

Science.gov (United States)

Bell, Anna; Althaus, Mike; Diener, Martin

2015-08-01

Histamine is a mast cell mediator released e.g. during food allergy. The aim of the project was to identify the effect of histamine on rat submucosal neurons and the mechanisms involved. Cultured submucosal neurons from rat colon express H1, H2 and H3 receptors as shown by immunocytochemical staining confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) with messenger RNA (mRNA) isolated from submucosal homogenates as starting material. Histamine evoked a biphasic rise of the cytosolic Ca(2+) concentration in cultured submucosal neurons, consisting in a release of intracellularly stored Ca(2+) followed by an influx from the extracellular space. Although agonists of all three receptor subtypes evoked an increase in the cytosolic Ca(2+) concentration, experiments with antagonists revealed that mainly H1 (and to a lesser degree H2) receptors mediate the response to histamine. In coculture experiments with RBL-2H3 cells, a mast cell equivalent, compound 48/80, evoked an increase in the cytosolic Ca(2+) concentration of neighbouring neurons. Like the response to native histamine, the neuronal response to the mast cell degranulator was strongly inhibited by the H1 receptor antagonist pyrilamine and reduced by the H2 receptor antagonist cimetidine. In rats sensitized against ovalbumin, exposure to the antigen induced a rise in short-circuit current (I sc) across colonic mucosa-submucosa preparations without a significant increase in paracellular fluorescein fluxes. Pyrilamine strongly inhibited the increase in I sc, a weaker inhibition was observed after blockade of protease receptors or 5-lipoxygenase. Consequently, H1 receptors on submucosal neurons seem to play a pivotal role in the communication between mast cells and the enteric nervous system.

Olopatadine Suppresses the Migration of THP-1 Monocytes Induced by S100A12 Protein

Directory of Open Access Journals (Sweden)

2006-01-01

Full Text Available Olopatadine hydrochloride (olopatadine is an antiallergic drug with histamine H 1 receptor antagonistic activity. Recently, olopatadine has been shown to bind to S100A12 which is a member of the S100 family of calcium-binding proteins, and exerts multiple proinflammatory activities including chemotaxis for monocytes and neutrophils. In this study, we examined the possibility that the interaction of olopatadine with S100A12 inhibits the proinflammatory effects of S100A12. Pretreatment of olopatadine with S100A12 reduced migration of THP-1, a monocyte cell line, induced by S100A12 alone, but did not affect recombinant human regulated upon activation, normal T cell expressed and secreted (RANTES-induced migration. Amlexanox, which also binds to S100A12, inhibited the THP-1 migration induced by S100A12. However, ketotifen, another histamine H 1 receptor antagonist, had little effect on the activity of S100A12. These results suggest that olopatadine has a new mechanism of action, that is, suppression of the function of S100A12, in addition to histamine H 1 receptor antagonistic activity.

Identification of transplanted pancreatic islet cells by radioactive Dithizone-[131I]-Histamine conjugate. Preliminary report

International Nuclear Information System (INIS)

Garnuszek, P.; Licinska, I.; Mazurek, A.P.; Mrozek, A.; Wardawa, A.; Fiedor, P.S.

2000-01-01

Background: The unique mechanism of dithizone action in the interior of the viable pancreatic islet suggests the possible development of a specific radiopharmaceutical that may have a potential clinical application in the diagnosis of the pancreatic organ allografts or islets rejection. The radiodiagnostic properties of the newly developed radioactive analogue of dithizone, i.e. Dithizone-[131I]-Histamine conjugate have been evaluated in the present study. METHODS: The four islet cells transplantation models were chosen for this purpose. The most important feature of the Dithizone-[131I]-Histamine conjugate is its possessed ability of zinc chelation. As was presented in the recent study, the conjugate stains pink-reddish the isolated pancreatic islets in vitro. Among the studied transplantation models, only the islets grafting under testis capsule enabled determination of the pancreatic islets in rats by radioactive Dithizone-[131I]-Histamine conjugate. The level of the radioactivity in the recipient testis (right) was almost two times higher compared to the controls (0.24 v. 0.13% ID/g, respectively). CONCLUSIONS: These preliminary data demonstrate the ability of the developed radioactive analogue of dithizone for in vivo identification of transplanted pancreatic islets, and suggests a potential clinical application of the radiodithizone in the diagnosis of the pancreatic islet rejection. (author)

Measuring histamine and cytokine release from basophils and mast cells

DEFF Research Database (Denmark)

Jensen, Bettina M; Falkencrone, Sidsel; Skov, Per S

2014-01-01

Basophils and mast cells are known for their capability to release both preformed and newly synthesized inflammatory mediators. In this chapter we describe how to stimulate and detect histamine released from basophils in whole blood, purified basophils, in vitro cultured mast cells, and in situ...... skin mast cells. We also give an example of an activation protocol for basophil and mast cell cytokine release and discuss approaches for cytokine detection....

Dependence of anaphylactic histamine release from rat mast cells on cellular energy metabolism

DEFF Research Database (Denmark)

Johansen, Torben

1981-01-01

The relation between anaphylactic histamine release and the adenosine triphosphate (ATP) content of the mast cells was studied. The cells were incubated with glycolytic (2-deoxyglucose) and respiratory inhibitors (antimycin A and oligomycin) in order to decrease the ATP content of the cells prior...... to initiation of the release process by the antigen-antibody reaction. The secretory capacity of mast cells was less related to the cellular level of ATP at the time of activation of the release process by the antigen-antibody reaction than to the rate of cellular energy supply. Furthermore, mast cells were...... pretreated with 2-deoxyglucose. The release of histamine from these cells was reduced when respiratory inhibitors were added to the cell suspension 5 to 20 sec after exposure of the cells to antigen. This may indicate that the secretory process requires energy, and it seems necessary that energy should...

Relevance of histamine and tryptase concentrations in nasal secretions after nasal challenges with phosphate buffered saline and allergen

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D. Wang

1995-01-01

Full Text Available In this prospective study, a quantitative determination of histamine and tryptase in nasal secretions after nasal phosphate buffered saline (PBS and allergen challenge was performed in 18 atopic patients who were compared with ten non-allergic healthy volunteers. The aim of the study was to determine the normal and pathological concentrations of these important mediators in nasal secretions. The second objective was to test the relevance of these two mast cell secreted mediators after nasal challenge. Results showed that the concentrations of tryptase in almost all samples were under the minimal detection limit (< 0.5 μU/g and only a sigrtificant increase of tryptase (median, 28 μU/g occurred immediately after nasal allergen challenge in the patient group. Histamine concentration significantly increased after every nasal PBS challenge (median, 69 ng/g after first PBS challenge and 165 ng/g after second PBS challenge in the control group, as well as in the patient group after both PBS (median, 69 ng/g and allergen (median, 214 ng/g challenge. On the other hand, a rapid onset of sneezing and increase in nasal airway resistance was experienced only in the patient group after nasal allergen challenge, but did not occur after PBS challenge even though the histamine concentrations significantly increased in both groups. This study suggests that tryptase is a more preferable marker than histamine in quantitative monitoring of mast cell activation especially during the early phase nasal allergic reaction.

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

International Nuclear Information System (INIS)

Brown, M.J.; Ind, P.W.; Causon, R.; Lee, T.H.

1982-01-01

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 (/sup 3/H)-methylhistamine in the presence of histamine-N-methyltransferase and (/sup 3/H)-S-adenosyl-L-methionine. In this assay, the separation of excess (/sup 3/H)-S-adenosyl-L-methionine from (/sup 3/H)-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 (/sup 3/H)-S-adenosyl-L-methionine. A further aliquot, with an added standard of 200 ng/ml histamine, was incubated with histamine-N-methyl-transferase and (/sup 14/C)-S-adenosyl-L-methionine. This standard was converted to (/sup 14/C)-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

Synthesis of Gallic Acid Analogs as Histamine and Pro-Inflammatory Cytokine Inhibitors for Treatment of Mast Cell-Mediated Allergic Inflammation.

Science.gov (United States)

Fei, Xiang; Je, In-Gyu; Shin, Tae-Yong; Kim, Sang-Hyun; Seo, Seung-Yong

2017-05-29

Gallic acid (3,4,5-trihydroxybenzoic acid), is a natural product found in various foods and herbs that are well known as powerful antioxidants. Our previous report demonstrated that it inhibits mast cell-derived inflammatory allergic reactions by blocking histamine release and pro-inflammatory cytokine expression. In this report, various amide analogs of gallic acid have been synthesized by introducing different amines through carbodiimide-mediated amide coupling and Pd/C-catalyzed hydrogenation. These compounds showed a modest to high inhibitory effect on histamine release and pro-inflammatory cytokine expression. Among them, the amide bearing ( S )-phenylglycine methyl ester 3d was found to be more active than natural gallic acid. Further optimization yielded several ( S )- and ( R )-phenylglycine analogs that inhibited histamine release in vitro. Our findings suggest that some gallamides could be used as a treatment for allergic inflammatory diseases.

Nitroglycerin-induced headache is not dependent on histamine release

DEFF Research Database (Denmark)

Iversen, Helle Klingenberg; Olesen, J

1994-01-01

The molecular mechanisms of migraine pain have not yet been clarified. Monoamine and the peptide neurotransmitters involved in neurogenic inflammation do not cause significant head pain. Our previous studies of glyceryl trinitrate (GTN) and histamine-induced headaches have suggested that nitric...... in the cascade of intracellular reactions triggered by NO. These novel observations change current views on vascular headache mechanisms and the importance of NO as an initiator of the migraine attacks dictates new approaches to the pharmacological treatment of migraine and other vascular headaches....

Short-term desensitization of the histamine H1 receptor in human HeLa cells : involvement of protein kinase C dependent and independent pathways

NARCIS (Netherlands)

Smit, M J; Bloemers, S M; Leurs, R; Tertoolen, L G; Bast, A; de Laat, S W; Timmerman, H

1992-01-01

1. In this study we have investigated the effects of short-term exposure of cells to histamine on the subsequent H1 receptor responsiveness in HeLa cells, using Ca2+ fluorescence microscopy and video digital imaging. 2. In HeLa cells, histamine (100 microM) induces an immediate H1 receptor-mediated

Molecular and functional profiling of histamine receptor-mediated calcium ion signals in different cell lines.

Science.gov (United States)

Meisenberg, Annika; Kaschuba, Dagmar; Balfanz, Sabine; Jordan, Nadine; Baumann, Arnd

2015-10-01

Calcium ions (Ca(2+)) play a pivotal role in cellular physiology. Often Ca(2+)-dependent processes are studied in commonly available cell lines. To induce Ca(2+) signals on demand, cells may need to be equipped with additional proteins. A prominent group of membrane proteins evoking Ca(2+) signals are G-protein coupled receptors (GPCRs). These proteins register external signals such as photons, odorants, and neurotransmitters and convey ligand recognition into cellular responses, one of which is Ca(2+) signaling. To avoid receptor cross-talk or cross-activation with introduced proteins, the repertoire of cell-endogenous receptors must be known. Here we examined the presence of histamine receptors in six cell lines frequently used as hosts to study cellular signaling processes. In a concentration-dependent manner, histamine caused a rise in intracellular Ca(2+) in HeLa, HEK 293, and COS-1 cells. The concentration for half-maximal activation (EC50) was in the low micromolar range. In individual cells, transient Ca(2+) signals and Ca(2+) oscillations were uncovered. The results show that (i) HeLa, HEK 293, and COS-1 cells express sufficient amounts of endogenous receptors to study cellular Ca(2+) signaling processes directly and (ii) these cell lines are suitable for calibrating Ca(2+) biosensors in situ based on histamine receptor evoked responses. Copyright © 2015 Elsevier Inc. All rights reserved.

Influence of preseasonal treatment with L-tyrosine-adsorbed allergoids on IgE-mediated histamine release from basophils of children suffering from allergic diseases.

Science.gov (United States)

Wegner, F; Fenkes, A; Stemmann, E A; Reinhardt, D

1981-04-01

In 10 children suffering from allergic pollinosis and/or asthma, a preseasonal hyposensitization scheme with 3 weekly injections of a glutaraldehyde-modified, tyrosine-adsorbed grass-pollen allergen reduced the histamine release from basophils in response to increasing concentrations of antigen. The decrease in histamine release which occurred 1 week after the injection course was even maintained during the pollen season. The inhibition was only obtained when basophils were incubated with the serum of patients, but not with the serum of normals, indicating that blocking antibodies may have occurred. In contrast to what has been observed in the treated patients' group, 5 patients, who were not included in the hyposensitization scheme, showed identical histamine release curves during the whole investigation period. Specific IgE did not increase after the treatment course and shows the same behaviour as the untreated patients. Thus, as treatment with glutaraldehyde modified, tyrosine-adsorbed allergoids is safe to administer, requires only 3 injections, reduces histamine release from basophils by production of "blocking" antibodies, it appears to be a useful tool in the hyposensitization treatment.

Fisetin inhibits IL-31 production in stimulated human mast cells: Possibilities of fisetin being exploited to treat histamine-independent pruritus.

Science.gov (United States)

Che, Denis Nchang; Cho, Byoung Ok; Shin, Jae Young; Kang, Hyun Ju; Kim, Young-Soo; Jang, Seon Il

2018-05-15

Interleukin-31 (IL-31) is a recently discovered cytokine that is tightly linked to the pathogenesis of pruritus seen in atopic dermatitis. Flavonoids, like fisetin, are naturally occurring molecules with antioxidant, cytoprotective, and anti-inflammatory actions. the present study sought to investigate whether fisetin modulates IL-31 and histamine release in human mast cells (HMC-1). HMC-1 cells were pretreated with fisetin at various doses and stimulated with phorbol-12-myristate 13-acetate and calcium ionophore A23187 (PI) for different time intervals. We evaluated IL-31 production and histamine release and signaling mechanism of the action of fisetin on IL-31 production. We also investigated the effects of fisetin on scratching behaviors in mice. Fisetin decreased PI-stimulated mRNA expression and production of IL-31 in HMC-1 cells. Fisetin inhibited PI-induced phosphorylation of mitogen-activated protein kinases that further suppressed nuclear factor (NF-κB) activation and translocation to the nucleus through the inhibition of IκB-α phosphorylation. Fisetin also prevented mast cell release of histamine in HMC-1 cells. Mice in-vivo studies show that fisetin reduced scratching behaviors in mice. These pharmacological actions of fisetin provide new suggestions that fisetin can be of potential use for the treatment of pruritus that cannot be treated with histamine receptor blockers alone. Copyright © 2018 Elsevier Inc. All rights reserved.

Mast cell mediators in citric acid-induced airway constriction of guinea pigs

International Nuclear Information System (INIS)

Lin, C.-H.; Lai, Y.-L.

2005-01-01

We demonstrated previously that mast cells play an important role in citric acid (CA)-induced airway constriction. In this study, we further investigated the underlying mediator(s) for this type of airway constriction. At first, to examine effects caused by blocking agents, 67 young Hartley guinea pigs were divided into 7 groups: saline + CA; methysergide (serotonin receptor antagonist) + CA; MK-886 (leukotriene synthesis inhibitor) + CA; mepyramine (histamine H 1 receptor antagonist) + CA; indomethacin (cyclooxygenase inhibitor) + CA; cromolyn sodium (mast cell stabilizer) + CA; and compound 48/80 (mast cell degranulating agent) + CA. Then, we tested whether leukotriene C 4 (LTC 4 ) or histamine enhances CA-induced airway constriction in compound 48/80-pretreated guinea pigs. We measured dynamic respiratory compliance (Crs) and forced expiratory volume in 0.1 s (FEV 0.1 ) during either baseline or recovery period. In addition, we detected histamine level, an index of pulmonary mast cell degranulation, in bronchoalveolar lavage (BAL) samples. Citric acid aerosol inhalation caused decreases in Crs and FEV 0.1 , indicating airway constriction in the control group. This airway constriction was significantly attenuated by MK-886, mepyramine, cromolyn sodium, and compound 48/80, but not by either methysergide or indomethacin. Both LTC 4 and histamine infusion significantly increased the magnitude of CA-induced airway constriction in compound 48/80-pretreated guinea pigs. Citric acid inhalation caused significant increase in histamine level in the BAL sample, which was significantly suppressed by compound 48/80. These results suggest that leukotrienes and histamine originating from mast cells play an important role in CA inhalation-induced noncholinergic airway constriction

Ciproxifan, an H3 receptor antagonist, improves short-term recognition memory impaired by isoflurane anesthesia.

Science.gov (United States)

Ding, Fang; Zheng, Limin; Liu, Min; Chen, Rongfa; Leung, L Stan; Luo, Tao

2016-08-01

Exposure to volatile anesthetics has been reported to cause temporary or sustained impairments in learning and memory in pre-clinical studies. The selective antagonists of the histamine H3 receptors (H3R) are considered to be a promising group of novel therapeutic agents for the treatment of cognitive disorders. The aim of this study was to evaluate the effect of H3R antagonist ciproxifan on isoflurane-induced deficits in an object recognition task. Adult C57BL/6 J mice were exposed to isoflurane (1.3 %) or vehicle gas for 2 h. The object recognition tests were carried at 24 h or 7 days after exposure to anesthesia to exploit the tendency of mice to prefer exploring novel objects in an environment when a familiar object is also present. During the training phase, two identical objects were placed in two defined sites of the chamber. During the test phase, performed 1 or 24 h after the training phase, one of the objects was replaced by a new object with a different shape. The time spent exploring each object was recorded. A robust deficit in object recognition memory occurred 1 day after exposure to isoflurane anesthesia. Isoflurane-treated mice spent significantly less time exploring a novel object at 1 h but not at 24 h after the training phase. The deficit in short-term memory was reversed by the administration of ciproxifan 30 min before behavioral training. Isoflurane exposure induces reversible deficits in object recognition memory. Ciproxifan appears to be a potential therapeutic agent for improving post-anesthesia cognitive memory performance.

NMDA receptor antagonists inhibit catalepsy induced by either dopamine D1 or D2 receptor antagonists.

Science.gov (United States)

Moore, N A; Blackman, A; Awere, S; Leander, J D

1993-06-11

In the present study, we investigated the ability of NMDA receptor antagonists to inhibit catalepsy induced by haloperidol, or SCH23390 and clebopride, selective dopamine D1 and D2 receptor antagonists respectively. Catalepsy was measured by recording the time the animal remained with its forepaws placed over a rod 6 cm above the bench. Pretreatment with either the non-competitive NMDA receptor antagonist, MK-801 (0.25-0.5 mg/kg i.p.) or the competitive antagonist, LY274614 (10-20 mg/kg i.p.) reduced the cataleptic response produced by haloperidol (10 mg/kg), SCH23390 (2.5-10 mg/kp i.p.) or clebopride (5-20 mg/kg i.p.). This demonstrates that NMDA receptor antagonists will reduce both dopamine D1 and D2 receptor antagonist-induced catalepsy. Muscle relaxant doses of chlordiazepoxide (10 mg/kg i.p.) failed to reduce the catalepsy induced by haloperidol, suggesting that the anticataleptic effect of the NMDA receptor antagonists was not due to a non-specific action. These results support the hypothesis that NMDA receptor antagonists may have beneficial effects in disorders involving reduced dopaminergic function, such as Parkinson's disease.

Enhanced basophil histamine release and neutrophil chemotactic activity predispose grain dust-induced airway obstruction.

Science.gov (United States)

Park, H; Jung, K; Kang, K; Nahm, D; Cho, S; Kim, Y

1999-04-01

The pathogenic mechanism of grain dust (GD)-induced occupational asthma (OA) remains unclear. To understand further the mechanism of GD-induced OA. Fifteen employees working in a same GD industry, complaining of work-related respiratory symptoms, were enrolled and were divided into two groups according to the GD-bronchoprovocation test (BPT) result: six positive responders were grouped as group III, nine negative responders as group II and five healthy controls as group I. Serum GD-specific immunoglobulin (Ig)E (sIgE), specific IgG (sIgG) and specific IgG4 (sIgG4) antibodies were detected by enzyme-linked immunosorbent assay. Basophil histamine release was measured by the autofluorometric method, and changes of serum neutrophil chemotactic activity were observed by the Boyden chamber method. For clinical parameters such as degree of airway hyperresponsiveness to methacholine, duration of respiratory symptoms, exposure duration, and prevalences of serum sIgE, sIgG and sIgG4 antibodies, there were no significant differences between group II and III (P > 0.05, respectively). Serum neutrophil chemotactic activity increased significantly at 30 min and decreased at 240 min after the GD-BPT in group III subjects (P 0.05). Basophil histamine release induced by GD was significantly higher in group III than those of group I or group II (P < 0.05, respectively), while minimal release of anti-IgG4 antibodies was noted in all three groups. These results suggest that enhanced basophil histamine release and serum neutrophil chemotactic activity might contribute to the development of GD-induced occupational asthma.

μ-1,2-Bis(diphenylphosphinoethane-κ2P:P′-bis{[1,2-bis(diphenylphosphinoethane-κ2P,P′]bromidocopper(I} acetone disolvate

Directory of Open Access Journals (Sweden)

Wen-Juan Shi

2008-10-01

Full Text Available In the crystal structure of the title compound, [Cu2Br2(dppe3]·2CH3COCH3 [dppe is 1,2-bis(diphenylphosphinoethane, C26H24P2], the two Cu centers are bridged by a dppe ligand and each metal center carries one chelating dppe unit, with the fourth coordination site available for the Br− anion. The molecule is centrosymmetric, with the center of symmetry located between the methylene C atoms of the bridging dppe ligand. The crystal structure is stabilized by intramolecular C—H...Br hydrogen bonds and intermolecular π–π interactions, with a centroid-to-centroid distance of 3.2055 (1 Å.

Evidence for dynamic network regulation of Drosophila photoreceptor function from mutants lacking the neurotransmitter histamine

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An eDau

2016-03-01

Full Text Available Synaptic feedback from interneurons to photoreceptors can help to optimize visual information flow by balancing its allocation on retinal pathways under changing light conditions. But little is known about how this critical network operation is regulated dynamically. Here, we investigate this question by comparing signaling properties and performance of wild-type Drosophila R1-R6 photoreceptors to those of the hdcJK910 mutant, which lacks the neurotransmitter histamine and therefore cannot transmit information to interneurons. Recordings show that hdcJK910 photoreceptors sample similar amounts of information from naturalistic stimulation to wild-type photoreceptors, but this information is packaged in smaller responses, especially under bright illumination. Analyses reveal how these altered dynamics primarily resulted from network overload that affected hdcJK910 photoreceptors in two ways. First, the missing inhibitory histamine input to interneurons almost certainly depolarized them irrevocably, which in turn increased their excitatory feedback to hdcJK910 R1-R6s. This tonic excitation depolarized the photoreceptors to artificially high potentials, reducing their operational range. Second, rescuing histamine input to interneurons in hdcJK910 mutant also restored their normal phasic feedback modulation to R1-R6s, causing photoreceptor output to accentuate dynamic intensity differences at bright illumination, similar to the wild-type. These results provide mechanistic explanations of how synaptic feedback connections optimize information packaging in photoreceptor output and novel insight into the operation and design of dynamic network regulation of sensory neurons.

Permeability of the small intestine after intra-arterial injection of histamine-type mediators and irradiation

International Nuclear Information System (INIS)

Kingham, J.G.C.; Loehry, C.A.

1976-01-01

Permeability and selectivity of rabbit small intestine were estimated by a perfusion technique after intra-arterial injection of histamine-type mediators and an intestinal dose of 1.5 Mr gamma irradiation. It was shown that the histamine-type mediators caused an increase in capillary permeability which produced an overall moderate increase in transmucosal permeability with a moderate loss of selectivity. Local intestinal irradiation caused a very marked increase in permeability and a profound loss of selectivity. It was felt that this was produced partly by an increase in capillary permeability but largely by damage to the epithelial basement membrane. It is concluded that the intestinal capillary endothelium is both rate-limiting and selective, though not to a major degree in either case. The epithelial basement membrane, however, appears to be both rate-limiting and markedly selective. (author)

KOMBINASI BUMBU DAN ASAP CAIR DALAM MEMINIMALKAN PEMBENTUKAN HISTAMIN PADA IKAN KEMBUNG PEREMPUAN (Rastrelliger neglectus ASAP [Combination of Spice and Liquid Smoke in Minimizing Histamine Formation in the Smoked Mackerel (Rastrelliger neglectus

Directory of Open Access Journals (Sweden)

Abu Bakar Tawali

2006-08-01

Full Text Available Four spices (clove, cinnamon, tamarind and ginger were combined and applied to produce smoked female mackerel. The use of liquid smoke was compared with redistilled liquid smoke. The result showed that there was lower histamine content in smoked fish treated with spices after the use of liquid smoke and redistilled liquid smoke at (1.00 – 1.20mg/100g compared with the raw material (1.55mg/100g. Histamine content in all treatments increased during storage from 0.96 – 1.13 mg/100g to 6.40 -20.29mg/100g. The phenol content decreased during storage from 2.19% - 2.44% to 0.72% - 0.84%. Using of liquid smoke in combination with spice as well as without spice,resulted in decreasing of the free fatty acid (FFA content until 20 days of storage then increased, whereas using redistilled liquid smoke, resulted decreased of FFA during 10 days storage before increased. Total psychrophilic microbe was not detectable at 0 and 10 days storage but then increased at 20 and 30 days storage to 6.5x103 – 10.1x103cfu/ml and 7.5x103 – 15.5x103cfu/ml, respectively. Overall, combination between clove-cinnamon and liquid smoke which was applied to female mackerel showed the best result i.e.: lower histamine content, lower FFA, lower total psychrophilic microbe and lower phenol content than other treatments. The acceptability of smoked fish treated with clove-cinnamon and liquid smoke after 30 days storage showed higher value than other treatments.

Histamine and tele-methylhistamine quantification in cerebrospinal fluid from narcoleptic subjects by liquid chromatography tandem mass spectrometry with precolumn derivatization.

Science.gov (United States)

Croyal, Mikaël; Dauvilliers, Yves; Labeeuw, Olivier; Capet, Marc; Schwartz, Jean-Charles; Robert, Philippe

2011-02-01

An ultra-performance liquid chromatography tandem mass spectrometry (UPLC™-MS/MS) assay was developed for the simultaneous analysis of histamine, its major metabolite tele-methylhistamine, and an internal standard (N-tele-(R)-α-dimethylhistamine) from human cerebrospinal fluid (CSF) samples. The method involves derivatization of primary amines with 4-bromobenzenesulfonyl chloride and subsequent analysis by reversed phase liquid chromatography with mass spectrometry detection and positive electrospray ionization. The separation of derivatized biogenic amines was achieved within 3.5 min on an Acquity® BEH C(18) column by elution with a linear gradient of acetonitrile/water/formic acid (0.1%). The assay was linear in the concentration range of 50-5000 pM for each amine (5.5-555 pg/ml for histamine and 6.25-625 pg/ml for tele-methylhistamine). For repeatability and precision determination, coefficients of variation (CVs) were less than 11.0% over the tested concentration ranges, within acceptance criteria. Thus, the developed method provides the rapid, easy, highly sensitive, and selective requirement to quantify these amines in human CSF. No significant difference was found in the mean ± standard error levels of these amines between a group of narcoleptic patients (histamine=392 ± 64 pM, tele-methylhistamine=2431 ± 461 pM, n=7) and of neurological control subjects (histamine=402 ± 72 pM, tele-methylhistamine=2209 ± 463 pM, n=32). Copyright © 2010 Elsevier Inc. All rights reserved.

[11C]TASP457, a novel PET ligand for histamine H3 receptors in human brain

International Nuclear Information System (INIS)

Kimura, Yasuyuki; Seki, Chie; Ikoma, Yoko; Ichise, Masanori; Kawamura, Kazunori; Takahata, Keisuke; Moriguchi, Sho; Nagashima, Tomohisa; Ishii, Tatsuya; Kitamura, Soichiro; Niwa, Fumitoshi; Endo, Hironobu; Yamada, Makiko; Higuchi, Makoto; Zhang, Ming-Rong; Suhara, Tetsuya

2016-01-01

The histamine H 3 receptors are presynaptic neuroreceptors that inhibit the release of histamine and other neurotransmitters. The receptors are considered a drug target for sleep disorders and neuropsychiatric disorders with cognitive decline. We developed a novel PET ligand for the H 3 receptors, [ 11 C]TASP0410457 ([ 11 C]TASP457), with high affinity, selectivity and favorable kinetic properties in the monkey, and evaluated its kinetics and radiation safety profile for quantifying the H 3 receptors in human brain. Ten healthy men were scanned for 120 min with a PET scanner for brain quantification and three healthy men were scanned for radiation dosimetry after injection of 386 ± 6.2 MBq and 190 ± 7.5 MBq of [ 11 C]TASP457, respectively. For brain quantification, arterial blood sampling and metabolite analysis were performed using high-performance liquid chromatography. Distribution volumes (V T ) in brain regions were determined by compartment and graphical analyses using the Logan plot and Ichise multilinear analysis (MA1). For dosimetry, radiation absorbed doses were estimated using the Medical Internal Radiation Dose scheme. [ 11 C]TASP457 PET showed high uptake (standardized uptake values in the range of about 3 - 6) in the brain and fast washout in cortical regions and slow washout in the pallidum. The two-tissue compartment model and graphical analyses estimated V T with excellent identification using 60-min scan data (about 16 mL/cm 3 in the pallidum, 9 - 14 in the basal ganglia, 6 - 9 in cortical regions, and 5 in the pons), which represents the known distribution of histamine H 3 receptors. For parametric imaging, MA1 is recommended because of minimal underestimation with small intersubject variability. The organs with the highest radiation doses were the pancreas, kidneys, and liver. The effective dose delivered by [ 11 C]TASP457 was 6.9 μSv/MBq. [ 11 C]TASP457 is a useful novel PET ligand for the investigation of the density of histamine H 3

Signaling transduction pathways involved in basophil adhesion and histamine release

DEFF Research Database (Denmark)

Sha, Quan; Poulsen, Lars K.; Gerwien, Jens

2006-01-01

Little is known about basophil with respect to the different signaling transduction pathways involved in spontaneous, cytokine or anti-IgE induced adhesion and how this compares to IgE-dependent and IgE-independent mediator secretion. The purpose of the present study was to investigate the roles...... of beta1 and beta2 integrins in basophil adhesion as well as hosphatidylinositol 3-kinase (PI3K), src-kinases and extracellular signal regulated kinase (ERK) 1/2 in basophil adhesion and histamine release (HR)....

The clinical effect of percutaneous histamine on allergic contact dermatitis elicited to fragrance mix

NARCIS (Netherlands)

R.L.P. Lijnen; Th. van Joost (Theo)

1995-01-01

textabstractHistamine (2-(4-imidazol)ethylamine) has been shown to downregulate cell-mediated reactions in vitro. However, the role of such downregulation in vivo has not yet extensively been studied in humans. In an attempt to gain more insight into this, we studied in vivo the effect of

Monocytes and neutrophils as 'bad guys' for the outcome of interleukin-2 with and without histamine in metastatic renal cell carcinoma--results from a randomised phase II trial

DEFF Research Database (Denmark)

Donskov, F; Hokland, M; Marcussen, N

2006-01-01

Histamine (HDC) inhibits formation and release of phagocyte-derived reactive oxygen species, and thereby protects natural killer (NK) and T cells against oxidative damage. Thus, the addition of histamine may potentially improve the efficacy of interleukin-2 (IL-2). We have explored this potential...... mechanism clinically in two randomised phase II trials in metastatic renal cell carcinoma (mRCC). In parallel with the clinical trial in Denmark (n=63), we obtained serial blood samples and tumour biopsies searching for a potential histamine effect in situ. At baseline and on-treatment weeks 3 and 8, we...

Indomethacin inhibits the increased airway responsiveness to histamine following inhalation of C5a des Arg in rabbits.

Science.gov (United States)

Berend, N; Armour, C L; Black, J L

1986-08-01

It has been shown that inhalation of C5a des Arg increases rabbit airway responsiveness to histamine and that this is associated with an influx of neutrophils into the airway walls. This study was undertaken to see if the augmented response to histamine can be blocked by the cyclo-oxygenase inhibitor indomethacin. Spontaneously breathing, anesthetised rabbits were studied in a volume displacement plethysmograph and pulmonary resistance (R1) was measured using the electrical subtraction technique. Histamine does response curves (HDR) were generated by measuring R1 after serial nubulisation of saline and histamine (1, 3, 10, 30 and 100 mg/ml). Aerosols of either saline or C5a des Arg (1.5 ug/ml) were then inhaled by the animals over a time period of 2 min. An HDR was then repeated 4 hours later. In 9 rabbits the inhalation of C5a des Arg resulted in an upward shift of the repeat HDR: the area under the HDR was significantly greater than under the first HDR (p less than 0.05). In 6 rabbits the repeat HDR 4 hours after saline was shifted downwards (N.S.) indicating some degree of tachyphylaxis. When rabbits were pretreated with indomethacin (5 mg/kg i.v.) the repeat HDR following either C5a des Arg (n = 7) or saline (n = 6) were also shifted downwards i.e., the increased airway responsiveness noted after C5a des Arg was abolished. There was no significant difference in baseline saline R1 during the first or second HDR in any group. These results suggest that the increased airway responsiveness following nebulisation of C5a des Arg may be due to release from neutrophils of products of the cyclo-oxygenase pathway.

N-acyl phosphatidylethanolamines affect the lateral distribution of cholesterol in membranes

DEFF Research Database (Denmark)

Térová, B.; Slotte, J.P.; Petersen, G.

2005-01-01

-acyl-POPE) or N-acyl-dipalmitoyl-sn-glycero-3-phosphatidylethanolamine (N-acyl-DPPE), and how the molecules interacted with cholesterol. The gel ¿ liquid crystalline transition temperature of sonicated N-acyl phosphatidylethanolamine vesicles in water correlated positively with the number of palmitic acyl chains...... in the molecules. Based on diphenylhexatriene steady state anisotropy measurements, the presence of 33 mol% cholesterol in the membranes removed the phase transition from N-oleoyl-POPE bilayers, but failed to completely remove it from N-palmitoyl-DPPE and N-palmitoyl-POPE bilayers, suggesting rather weak...... interaction of cholesterol with the N-saturated NAPEs. The rate of cholesterol desorption from mixed monolayers containing N-palmitoyl-DPPE and cholesterol (1:1 molar ratio) was much higher compared to cholesterol/DPPE binary monolayers, suggesting a weak cholesterol interaction with N-palmitoyl-DPPE also...

Suppressed histamine release from rat peritoneal mast cells by ultraviolet B irradiation: decreased diacylglycerol formation as a possible mechanism

International Nuclear Information System (INIS)

Danno, K.; Fujii, K.; Tachibana, T.; Toda, K.; Horio, T.

1988-01-01

This study was designed to investigate the effect of ultraviolet B (UVB) irradiation on mast cell functions. Purified mast cells obtained from rat peritoneal cavity were irradiated with UVB and subsequently exposed to a degranulator, compound 48/80, or the calcium ionophore A-23187. The amount of histamine released from mast cells measured by the enzyme isotopic assay was significantly decreased by UVB irradiation (100-400 mJ/cm2). Within this dose range, UVB alone was not cytotoxic to the cells because it did not induce histamine release. The suppression was observed when mast cells were subjected to degranulation without intervals after UVB irradiation, and even after 5 h postirradiation. The wavelength of 300 nm from a monochromatic light source showed the maximum effect. When mast cells prelabeled with [ 3 H]arachidonate were irradiated and challenged by compound 48/80, label accumulation in diacylglycerol produced by the phosphatidylinositol cycle was considerably decreased by UVB irradiation. From these results, we hypothesize that, within an adequate irradiation dose, UVB irradiation suppresses histamine release from mast cells, probably by causing noncytotoxic damage to the membrane phospholipid metabolism, which is tied to the degranulation mechanisms

Allisonella histaminiformans gen. nov., sp. nov. A novel bacterium that produces histamine, utilizes histidine as its sole energy source, and could play a role in bovine and equine laminitis.

Science.gov (United States)

Garner, Matthew R; Flint, Joseph F; Russell, James B

2002-12-01

When cattle and horses are fed large amounts of grain, histamine can accumulate in the gastrointestinal tract, and this accumulation can cause an acute inflammation of the hooves (laminitis). When ruminal fluid from dairy cattle fed grain supplements was serially diluted in anaerobic MRS medium containing histidine (50 mM), histamine was detected at dilutions as high as 10(-7). The histidine enrichments were then transferred successively in an anaerobic, carbonate-based medium (50 mM histidine) without glucose. The histamine producing bacteria could not be isolated from the rumens of cattle fed hay; however, histamine producing bacteria could be isolated the feces of cattle fed grain and the cecum of a horse. All of the histamine producing isolates had the same ovoid morphology. The cells stained Gram-negative and were resistant to the ionophore, monensin (25 microM). The doubling time was 110 min, and the yield was 1.5 mg cell protein per mmol histidine. The G+C content was 46.8%. Lysine was the only other amino acid used, but lysine did not allow growth if histidine was absent. Because carbohydrate and organic acid utilization was not detected, it appeared that the isolates used histidine decarboxylation as their sole mechanism of energy derivation. 16s rRNA gene sequencing indicated that the isolates were most closely related to low G+C Gram-positive bacteria (firmicutes), but similarities were < or = 94%. Because the most closely related bacteria (Dialister pneumonsintes, Megasphaera elsdenii and Selenomonas ruminantium) did not produce histamine from histidine, we propose that these histamine producing bacteria be assigned to a new genus, Allisonella, as Allisonella histaminiformans gen. nov., sp. nov. The type strain is MR2 (ATCC BAA610, DSM 15230).

Biogenic amine content, histamine-forming bacteria, and adulteration of pork in tuna sausage products.

Science.gov (United States)

Kung, Hsien-Feng; Tsai, Yung-Hsiang; Chang, Shih-Chih; Hong, Tang-Yao

2012-10-01

Twenty-five tuna sausage products were purchased from retail markets in Taiwan. The rates of occurrence of biogenic amines, histamine-forming bacteria, and adulteration by pork and poultry were determined. The average content of various biogenic amines in all tested samples was less than 2.0 mg/100 g (Makaira nigricans (blue marlin).

Nocturnal airflow obstruction, histamine, and the autonomic central nervous system in children with allergic asthma

NARCIS (Netherlands)

van Aalderen, W. M.; Postma, D. S.; Koëter, G. H.; Knol, K.

1991-01-01

A study was carried out to investigate whether an imbalance in the autonomic nervous system or release of histamine, or both, is responsible for the nocturnal increase in airflow obstruction in asthmatic children. The study comprised 18 children with allergic asthma, nine with (group 1) and nine

Staphylococcus aureus and influenza A virus stimulate human bronchoalveolar cells to release histamine and leukotrienes

DEFF Research Database (Denmark)

Clementsen, P; Bisgaard, H; Pedersen, M

1989-01-01

persons were stimulated with Staph. aureus no release of leukotriene C4 was found. The mediator release caused by bacteria and virus might be of importance for the exacerbation of bronchial asthma in upper respiratory tract infections, since histamine is assumed to increase the epithelial permeability...

Transglutaminase-catalyzed amination of pea protein peptides using the biogenic amines histamine and tyramine.

Science.gov (United States)

Lu, Xinyao; Hrynets, Yuliya; Betti, Mirko

2017-06-01

Biogenic amines (BAs) are produced by the enzymatic decarboxylation of amino acids, and are well-known for their toxicity to humans. This study describes a new method using microbial transglutaminase (MTGase) to covalently link BAs such as histamine (HIS) and tyramine (TYR) to the glutamine residues of alcalase-hydrolyzed pea protein (PPH). The incubation of PPH and HIS and TYR in the presence of MTGase at 37 °C led to the formation of conjugates, as determined by liquid chromatography, after derivatization with dansyl chloride. Seventy-six % of HIS and 65% of TYR were covalently incorporated to PPH by MTGase. The incubation of PPH and TYR in the presence of MTGase exhibited a 52% DPPH radical scavenging activity at 10 mg mL -1 . Conjugation via MTGase improved the antioxidant status by reducing lipid peroxidation. This study emphasizes that the application of MTGase can effectively reduce histamine and tyramine content while simultaneously enhancing antioxidative capacity of PPH. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Histamine, mast cells, and the enteric nervous system in the irritable bowel syndrome, enteritis, and food allergies

OpenAIRE

Wood, J D

2006-01-01

There is altered expression of histamine H1 and H2 receptor subtypes in mucosal biopsies from the terminal ileum and large intestine of patients with symptoms of food allergy and/or irritable bowel syndrome

Neurogenic mediators contribute to local edema induced by Micrurus lemniscatus venom

Science.gov (United States)

2017-01-01

Background/Aims Micrurus is one of the four snake genera of medical importance in Brazil. Coral snakes have a broad geographic distribution from the southern United States to Argentina. Micrurine envenomation is characterized by neurotoxic symptoms leading to dyspnea and death. Moreover, various local manifestations, including edema formation, have been described in patients bitten by different species of Micrurus. Thus, we investigated the ability of Micrurus lemniscatus venom (MLV) to induce local edema. We also explored mechanisms underlying this effect, focusing on participation of neuropeptides and mast cells. Methodology/Principal findings Intraplantar injection of MLV (1–10 μg/paw) in rats caused dose- and time-dependent edema with a peak between 15 min and 1 h after injection. MLV also induced degranulation of peritoneal mast cells (MCs). MC depletion by compound 48/80 markedly reduced MLV-induced edema. Pre-treatment (30 min) of rats with either promethazine a histamine H1 receptor antagonist or methysergide, a nonselective 5-HT receptor antagonist, reduced MLV-induced edema. However, neither thioperamide, a histamine H3/H4 receptor antagonist, nor co-injection of MLV with HOE-140, a BK2 receptor antagonist, altered the response. Depletion of neuropeptides by capsaicin or treatment of animals with NK1- and NK2-receptor antagonists (SR 140333 and SR 48968, respectively) markedly reduced MLV-induced edema. Conclusions/Significance In conclusion, MLV induces paw edema in rats by mechanisms involving activation of mast cells and substance P-releasing sensory C-fibers. Tachykinins NKA and NKB, histamine, and serotonin are major mediators of the MLV-induced edematogenic response. Targeting mast cell- and sensory C-fiber-derived mediators should be considered as potential therapeutic approaches to interrupt development of local edema induced by Micrurus venoms. PMID:29161255

Neurogenic mediators contribute to local edema induced by Micrurus lemniscatus venom.

Directory of Open Access Journals (Sweden)

Luciana Lyra Casais-E-Silva

2017-11-01

Full Text Available Micrurus is one of the four snake genera of medical importance in Brazil. Coral snakes have a broad geographic distribution from the southern United States to Argentina. Micrurine envenomation is characterized by neurotoxic symptoms leading to dyspnea and death. Moreover, various local manifestations, including edema formation, have been described in patients bitten by different species of Micrurus. Thus, we investigated the ability of Micrurus lemniscatus venom (MLV to induce local edema. We also explored mechanisms underlying this effect, focusing on participation of neuropeptides and mast cells.Intraplantar injection of MLV (1-10 μg/paw in rats caused dose- and time-dependent edema with a peak between 15 min and 1 h after injection. MLV also induced degranulation of peritoneal mast cells (MCs. MC depletion by compound 48/80 markedly reduced MLV-induced edema. Pre-treatment (30 min of rats with either promethazine a histamine H1 receptor antagonist or methysergide, a nonselective 5-HT receptor antagonist, reduced MLV-induced edema. However, neither thioperamide, a histamine H3/H4 receptor antagonist, nor co-injection of MLV with HOE-140, a BK2 receptor antagonist, altered the response. Depletion of neuropeptides by capsaicin or treatment of animals with NK1- and NK2-receptor antagonists (SR 140333 and SR 48968, respectively markedly reduced MLV-induced edema.In conclusion, MLV induces paw edema in rats by mechanisms involving activation of mast cells and substance P-releasing sensory C-fibers. Tachykinins NKA and NKB, histamine, and serotonin are major mediators of the MLV-induced edematogenic response. Targeting mast cell- and sensory C-fiber-derived mediators should be considered as potential therapeutic approaches to interrupt development of local edema induced by Micrurus venoms.

Homologous histamine H1 receptor desensitization results in reduction of H1 receptor agonist efficacy

NARCIS (Netherlands)

Leurs, R; Smit, M J; Bast, A; Timmerman, H

1991-01-01

Prolonged exposure of the guinea-pig intestinal longitudinal smooth muscle to histamine caused homologous desensitization of the H1 receptor, which led to reduced H1 receptor-mediated production of [3H]inositol phosphates as well as to reduced H1 agonist-induced contractions. [3H]Mepyramine binding

Enhanced incorporation of fatty acid into phosphatidyl choline that parallels histamine discharge in mast cells

International Nuclear Information System (INIS)

Castle, J.D.; Castle, A.M.; Ma, A.K.; Stukenbrok, H.

1984-01-01

Purified rat peritoneal and pleural mast cells preincubated briefly with radioactively labeled fatty acid were treated with A23187, which bypasses primary receptors in stimulating exocytosis. An enhanced incorporation of fatty acid into phosphatidyl choline (PC) that occurred in parallel with histamine release at 24-25 degrees C was observed and was initially proportional to the total amount of histamine discharged. Enhanced PC labeling and histamine secretion were also proportional at temperatures ranging from 17-37 degrees C. Both radioactive linoleic and palmitic acids were incorporated selectively at the beta-position of the glycerol backbone of PC. PC labeling by [3H]choline was not detectably different in control and stimulated cells, and phosphatidic acid did not exhibit selectively enhanced beta-acylation. Thus, the stimulated labeling in A23187-treated cells may occur secondary to the action of a phospholipase A2 that favors PC as a substrate. Other peritoneal cell types exhibit a very similar A23187-stimulated selective labeling of PC. Therefore, autoradiography has been used to provide a direct demonstration that in purified preparations, mast cells are the principal cell type engaged in A23187-elicited incorporation of fatty acid into PC. The efficacy of this approach has relied on special procedures devised to obtain significantly different autoradiographic grain densities between control and stimulated preparations that can be attributed to differences in the level of [3H]palmitate-labeled PC. Preliminary tests using compound 48/80 as a secretory stimulus for mast cells have identified a similar selectively enhanced PC labeling. In either case, however, consideration of possible relationships between PC metabolism and the secretory process are premature since they have not been tested directly

Activation of histamine H4 receptor inhibits TNFα/IMD-0354-induced apoptosis in human salivary NS-SV-AC cells.

Science.gov (United States)

Stegajev, Vasili; Kouri, Vesa-Petteri; Salem, Abdelhakim; Rozov, Stanislav; Stark, Holger; Nordström, Dan C E; Konttinen, Yrjö T

2014-12-01

Apoptosis is involved in the pathogenesis of Sjögren's syndrome (SS), an autoimmune disease affecting exocrine glands. Our recent studies revealed diminished histamine H4 receptor (H₄R) expression and impaired histamine transport in the salivary gland epithelial cells in SS. The aim was now to test if nanomolar histamine and high-affinity H₄R signaling affect apoptosis of human salivary gland epithelial cell. Simian virus 40-immortalized acinar NS-SV-AC cells were cultured in serum-free keratinocyte medium ± histamine H₄R agonist HST-10. Expression and internalization of H₄R were studied by immunofluorescence staining ± clathrin inhibitor methyl-β-cyclodextrin (MβCD). Apoptosis induced using tumor necrosis factor-α with nuclear factor-κB inhibitor IMD-0354 was studied using phase contrast microscopy, Western blot, flow cytometry and polymerase chain reaction (qRT-PCR). HST-10-stimulated H₄R internalization was inhibited by MβCD. Western blotting revealed diminished phosphorylated c-Jun N-terminal kinase JNK, but unchanged levels of phosphorylated extracellular signal regulated kinase pERK1/2 in H₄R-stimulated samples compared to controls. qRT-PCR showed up-regulated expression of anti-apoptotic B cell lymphoma-extra large/Bcl-xL mRNAs and proteins, whereas pro-apoptotic Bcl-2-associated X protein/BAX remained unchanged in H4R-stimulated samples. H₄R stimulation diminished cleavage of PARP and flow cytometry showed significant dose-dependent inhibitory effect of H₄R stimulation on apoptosis. As far as we know this is the first study showing inhibitory effect of H₄R activation on apoptosis of human salivary gland cells. Diminished H₄R-mediated activation may contribute to loss of immune tolerance in autoimmune diseases and in SS in particular.

Histamine mediates the pro-inflammatory effect of latex of Calotropis procera in rats

Directory of Open Access Journals (Sweden)

Yatin M. Shivkar

2003-01-01

Full Text Available Introduction: Calotropis procera is known to produce contact dermatitis and the latex of this plant produces intense inflammation when injected locally. However, the precise mode of its pro-inflammatory effect is not known. In present study we have pharmacologically characterized the inflammation induced by latex of C. procera in a rat paw edema model and determined the role of histamine in latex-induced inflammation.

Carbon adaptation influence the antagonistic ability of ...

African Journals Online (AJOL)

Jane

2011-10-24

Oct 24, 2011 ... INTRODUCTION. The use of antagonistic bacteria to control soil-borne ... plant was used to evaluate the antifungal activities of antagonistic bacteria. ..... antagonistic bacteria and cloning of its phenazine carboxylic acid genes.

Identification of novel β-lactams and pyrrolidinone derivatives as selective Histamine-3 receptor (H3R) modulators as possible anti-obesity agents.

Science.gov (United States)

Ghoshal, Anirban; Kumar, Ajeet; Yugandhar, Doddapaneni; Sona, Chandan; Kuriakose, Sunu; Nagesh, Kommu; Rashid, Mamunur; Singh, Sandeep K; Wahajuddin, Muhammad; Yadav, Prem N; Srivastava, Ajay K

2018-05-25

Four series of structurally related β-lactams, 2,5-pyrrolidinediones, azaspirodecatrienediones (ASDT) and dihydropyrroloquinoxalinetriones (DPQT) were synthesized by utilizing post-Ugi modifications in one-pot, and their activity towards human histamine-3 receptor (H3R) was evaluated. Out of 94 compounds, screened against histamine-3 receptor (H3R), 21 compounds showed high H3R selective agonist property with EC 50 values ranging from 187 nM to 0.1 nM, whereas none of the compound was found to have the affinity towards other receptors of histamine family such as histamine H1, H2, and H4 receptor. All active compounds have no assay interference activity as determined by in-silico analysis and receptor independent luciferase assay and cell cytotoxicity assay. Given the important role of H3R in hypophagia, we also evaluated the in vivo effect of the representative compound 6k on the cumulative food intake in diet induce obese C57BL6/J mice. Interestingly, we observed that single dose administration (20 mg/kg, intraperitoneal injection) of 6k significantly suppressed cumulative food intake, while no significant effect was observed at 10 mg/kg. These results suggest that β-lactams, 2,5-pyrrolidinediones, azaspirodecatrienediones (ASDT) and dihydropyrroloquinoxalinetriones (DPQT) could be useful for the development of anti-obesity candidate drugs. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Estimation of adenosine triphosphate utilization of rat mast cells during and after anaphylactic histamine secretion

DEFF Research Database (Denmark)

Johansen, Torben

1990-01-01

during the time period of histamine secretion and immediately after its completion. During secretion the additional ATP-utilization above the basal level of ATP-synthesis was 0.51 pmol/10(3) cells. 2.5 min after cell activation, the rate of additional ATP-utilization was 0.30 pmol/10(3) cells...

Stimulant effects of adenosine antagonists on operant behavior: differential actions of selective A2A and A1 antagonists

Science.gov (United States)

Randall, Patrick A.; Nunes, Eric J.; Janniere, Simone L.; Stopper, Colin M.; Farrar, Andrew M.; Sager, Thomas N.; Baqi, Younis; Hockemeyer, Jörg; Müller, Christa E.

2012-01-01

Rationale Adenosine A2A antagonists can reverse many of the behavioral effects of dopamine antagonists, including actions on instrumental behavior. However, little is known about the effects of selective adenosine antagonists on operant behavior when these drugs are administered alone. Objective The present studies were undertaken to investigate the potential for rate-dependent stimulant effects of both selective and nonselective adenosine antagonists. Methods Six drugs were tested: two nonselective adenosine antagonists (caffeine and theophylline), two adenosine A1 antagonists (DPCPX and CPT), and two adenosine A2A antagonists (istradefylline (KW6002) and MSX-3). Two schedules of reinforcement were employed; a fixed interval 240-s (FI-240 sec) schedule was used to generate low baseline rates of responding and a fixed ratio 20 (FR20) schedule generated high rates. Results Caffeine and theophylline produced rate-dependent effects on lever pressing, increasing responding on the FI-240 sec schedule but decreasing responding on the FR20 schedule. The A2A antagonists MSX-3 and istradefylline increased FI-240 sec lever pressing but did not suppress FR20 lever pressing in the dose range tested. In fact, there was a tendency for istradefylline to increase FR20 responding at a moderate dose. A1 antagonists failed to increase lever pressing rate, but DPCPX decreased FR20 responding at higher doses. Conclusions These results suggest that adenosine A2A antagonists enhance operant response rates, but A1 antagonists do not. The involvement of adenosine A2A receptors in regulating aspects of instrumental response output and behavioral activation may have implications for the treatment of effort-related psychiatric dysfunctions, such as psychomotor slowing and anergia in depression. PMID:21347642

Mastitis Modifies the Biogenic Amines Profile in Human Milk, with Significant Changes in the Presence of Histamine, Putrescine and Spermine.

Directory of Open Access Journals (Sweden)

Marta Perez

Full Text Available Biogenic amines (BAs are low molecular weight nitrogenous organic compounds with different biological activities. Putrescine, spermidine and spermine are essential for the development of the gut and immune system of newborns, and are all found in human milk. Little is known, however, about the role of histamine, tyramine or cadaverine in breast milk. Nor is it known whether mastitis alters the BA composition of milk. The BA profile of human milk, and the influence of mastitis on BA concentrations, were therefore investigated. Putrescine, spermidine and spermine were the main BAs detected. In mastitis-affected milk, the concentrations of putrescine, spermine and histamine were higher.

Basophil histamine release to Amoxicilloyl-poly-L-lysine compared to amoxicillin in patients with IgE-mediated allergic reactions to amoxicillin

DEFF Research Database (Denmark)

Arribas, F; Falkencrone, S; Sola, J

2017-01-01

BACKGROUND: Amoxicillin (AX) is the betalactam most often involved in IgE-mediated reactions and the diagnosis is mainly based on skin testing (ST) although without optimal sensitivity. We have produced a newly AX derivative, amoxicilloyl-poly-L-lysine (APL), and have analysed its IgE recognition...... with AX or APL. Histamine released was determined and expressed as ng of histamine release/mL blood. RESULTS: Patients clinical symptoms were anaphylaxis (N=9), urticaria (N=7), erythema (N=2) and not defined immediate reactions (N=1). The median time interval between reaction and study was 90 days (IQR...

Ranitidine as adjuvant treatment in colorectal cancer

DEFF Research Database (Denmark)

Nielsen, Hans Jørgen; Christensen, Ib Jarle; Moesgaard, F

2002-01-01

BACKGROUND: Results from short-term studies of histamine type 2 (H2) receptor antagonists on survival of patients with solid tumours are debatable. In this study the efficacy of the H2-receptor antagonist ranitidine on long-term survival of patients with colorectal cancer was evaluated. METHODS...... curative resection of colorectal cancer and who do not receive perioperative blood transfusion and do not develop postoperative infectious complications....

Differential regulation of histamine- and bradykinin-stimulated phospholipase C in adrenal chromaffin cells: evidence for involvement of different protein kinase C isoforms.

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Sena, C M; Rosário, L M; Parker, P J; Patel, V; Boarder, M R

1996-03-01

In this report we investigate the isoforms of protein kinase C (PKC) present in cultured adrenal chromaffin cells with respect to their modulation by treatment with phorbol ester and their possible differential involvement in the regulation of responses to histamine and bradykinin. The presence of individual isoforms of PKC was investigated by using eight isoform specific antisera, as a result of which PKC-alpha, epsilon, and zeta were identified. To characterize down-regulation of these enzymes, cells were incubated for 6-48 h with 1 microM phorbol myristate acetate (PMA). PKC-epsilon down-regulated more rapidly than PKC-alpha. At 12 h, PMA pretreatment, for example, PKC-epsilon was maximally down-regulated (23 +/- 4% of controls), whereas PKC-alpha was unchanged. PKC-alpha showed partial down-regulation by 24 h of PMA pretreatment. PKC-zeta did not down-regulate at any of the times tested. Translocation from cytosol to membrane in response to PMA was also more rapid for PKC-epsilon than for PKC-alpha. The accumulation of total 3H-inositol (poly) phosphates in response to bradykinin or histamine was essentially abolished by prior treatment with 10-min PMA treatment (1 microM). However, with 12-h exposure to PMA, the bradykinin response was restored to the level seen with no prior PMA exposure. The histamine response showed no recovery by 12 h of PMA, but showed partial recovery by 24 h of PMA pretreatment. These observations showed that the restoration of the response to bradykinin corresponds to the loss of PKC-epsilon, whereas the restoration of the histamine response corresponds to the loss of PKC-alpha. This picture was confirmed with further studies on cytosolic Ca2+. The results show that chromaffin cells exhibit an unusual pattern of down-regulation of PKC isoforms on prolonged exposure to PMA, and that there is a differential effect of exposure to PMA on the histamine and bradykinin responses, suggesting that different PLC-linked receptors in chromafin

Exercise-induced bronchoconstriction: The effects of montelukast, a leukotriene receptor antagonist

Directory of Open Access Journals (Sweden)

James P Kemp

2009-11-01

Full Text Available James P KempClinical Professor of Pediatrics, Division of Immunology and Allergy, University of California School of Medicine, San Diego, CA, USAAbstract: Exercise-induced bronchoconstriction (EIB is very common in both patients with asthma and those who are otherwise thought to be normal. The intensity of exercise as well as the type of exercise is important in producing symptoms. This may make some types of exercise such as swimming more suitable and extended running more difficult for patients with this condition. A better understanding of EIB will allow the physician to direct the patient towards a type of exercise and medications that can result in a more active lifestyle without the same concern for resulting symptoms. This is especially important for schoolchildren who are usually enrolled in physical education classes and elite athletes who may desire to participate in competitive sports. Fortunately several medications (short- and long-acting β2-agonists, cromolyn, nedocromil, inhaled corticosteroids, and more recently leukotriene modifiers have been shown to be effective in preventing or attenuating the effects of exercise in many patients. In addition, inhaled β2-agonists have been shown to quickly reverse the airway obstruction that develops in patients and continue to be the reliever medications of choice. Inhaled corticosteroids are increasingly being recommended as regular therapy now that the role of inflammation and airway injury has been identified in EIB. With the discovery that there is a release of mediators such as histamine and leukotrienes from cells in the airway following exercise with resulting airway obstruction in susceptible individuals, interest has turned to attenuating their effects with mediator antagonists especially those that block the effects of leukotrienes. Studies with an oral leukotriene antagonist, montelukast, have shown beneficial effects in adults and children aged as young as 6 years with EIB

Excitatory amino acid receptor antagonists

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Johansen, T N; Frydenvang, Karla Andrea; Ebert, B

1997-01-01

We have previously shown that (RS)-2-amino-2-(5-tert-butyl-3-hydroxyisoxazol-4-yl)acetic acid (ATAA) is an antagonist at N-methyl-D-aspartic acid (NMDA) and (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) receptors. We have now resolved ATAA via diastereomeric salt formation......)-phenylethylamine salt of N-BOC-(R)-ATAA. Like ATAA, neither (R)- nor (S)-ATAA significantly affected (IC50 > 100 microM) the receptor binding of tritiated AMPA, kainic acid, or (RS)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid, the latter being a competitive NMDA antagonist. Electrophysiological experiments......, using the rat cortical wedge preparation, showed the NMDA antagonist effect as well as the AMPA antagonist effect of ATAA to reside exclusively in the (R)-enantiomer (Ki = 75 +/- 5 microM and 57 +/- 1 microM, respectively). Neither (R)- nor (S)-ATAA significantly reduced kainic acid-induced excitation...

Long-Range Intramolecular Electronic Communication in a Trinuclear Ruthenium Tropolonate Complex.

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Yoshida, Jun; Kuwahara, Kyohei; Suzuki, Kota; Yuge, Hidetaka

2017-02-20

Dinuclear and trinuclear ruthenium complexes, [Ru(trop) 2 (C 2 trop)Ru(dppe)Cp] [2b; trop = tropolonato, C 2 trop = ethynyltropolonato, dppe = 1,2-bis(diphenylphosphino)ethane] and [Ru(trop){(C 2 trop)Ru(dppe)Cp} 2 ] (3), were synthesized, and their electronic and electrochemical properties were investigated in comparison with our previously reported complex [Ru(acac) 2 (C 2 trop)Ru(dppe)Cp] (2a). The electron-donating Ru II (dppe)Cp unit and electron-accepting Ru III O 6 unit are connected by C 2 trop in these complexes. 2a incorporates acetylacetonate as an ancillary ligand, while 2b and 3 incorporate tropolonate as an ancillary ligand. Every complex, 2a, 2b, and 3, exhibits similar UV-vis-near-IR (NIR) absorption spectra, demonstrating the lack of explicit intramolecular electronic communication between the units at least in the neutral state. The weak NIR absorption in 2a further diminished upon electrochemical oxidation, indicating almost no electronic communication between the units. In contrast, 2b and 3 exhibit broad NIR absorptions upon oxidation. Additionally, 3 exhibits four stepwise redox couples in the electrochemical study, which are formally attributed to [Ru II (trop) 3 ] - /[Ru III (trop) 3 ], two [Ru II (dppe)Cp]/[Ru III (dppe)Cp] + , and [Ru III (trop) 3 ]/[Ru IV (trop) 3 ] + couples. Clear separation of the redox couples attributed to the two terminal [Ru(dppe)Cp] units demonstrates the thermodynamic stability of the intermediate oxidation states with respect to disproportionation. Further electrochemical studies using an electrolyte including perfluorinated weakly coordinating anions and density functional theory/time-dependent density functional theory calculations confirmed the effect of ancillary ligands, acetylacetonate and tropolonate. In the case of 2a, electronic delocalization over the whole complex, especially over the [Ru(acac) 2 (trop)] unit, appears to be small. In contrast, the electronic communication between [Ru(dppe)Cp] and [Ru

NOCTURNAL AIR-FLOW OBSTRUCTION, HISTAMINE, AND THE AUTONOMIC CENTRAL-NERVOUS-SYSTEM IN CHILDREN WITH ALLERGIC-ASTHMA

NARCIS (Netherlands)

VANAALDEREN, WMC; POSTMA, DS; KOETER, GH; KNOL, K

A study was carried out to investigate whether an imbalance in the autonomic nervous system or release of histamine, or both, is responsible for the nocturnal increase in airflow obstruction in asthmatic children. The study comprised 18 children with allergic asthma,nine with (group 1) and nine

Complement-induced histamine release from human basophils. III. Effect of pharmacologic agents.

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Hook, W A; Siraganian, R P

1977-02-01

Human serum activated with zymosan generates a factor (C5a) that releases histamine from autologous basophils. Previously we have presented evidence that this mechanism for C5a-induced release differs from IgE-mediated reactions. The effect of several pharmacologic agents known to alter IgE-mediated release was studied to determine whether they have a similar action on serum-induced release. Deuterium oxide (D2O), which enhances allergic release, inhibited in a concentration-dependent fashion the serum-induced reaction at incubation temperatures of 25 and 32 degrees C. The colchicine-induced inhibition was not reversed by D2O. Cytochalasin B, which gives a variable enhancement of IgE-mediated release, had a marked enhancing effect on the serum-induced reaction in all subjects tested. The following agents known to inhibit the IgE-mediated reaction also inhibited serum-induced release at 25 degrees C: colchicine, dibutyryl cyclic AMP, aminophylline, isoproterenol, cholera toxin, chlorphenesin, diethylcarbamazine, and 2-deoxy-D-glucose. These results suggest that the serum-induced release is modulated by intracellular cyclic AMP, requires energy, and is enhanced by the disruption of microfilaments. The lack of an effect by D2O would suggest that microtubular stabilization is not required. The data can be interpreted to indicate that IgE- and C5a-mediated reactions diverge at a late stage in the histamine release pathway.

Dendrogenin A arises from cholesterol and histamine metabolism and shows cell differentiation and anti-tumour properties.

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de Medina, Philippe; Paillasse, Michael R; Segala, Gregory; Voisin, Maud; Mhamdi, Loubna; Dalenc, Florence; Lacroix-Triki, Magali; Filleron, Thomas; Pont, Frederic; Saati, Talal Al; Morisseau, Christophe; Hammock, Bruce D; Silvente-Poirot, Sandrine; Poirot, Marc

2013-01-01

We previously synthesized dendrogenin A and hypothesized that it could be a natural metabolite occurring in mammals. Here we explore this hypothesis and report the discovery of dendrogenin A in mammalian tissues and normal cells as an enzymatic product of the conjugation of 5,6α-epoxy-cholesterol and histamine. Dendrogenin A was not detected in cancer cell lines and was fivefold lower in human breast tumours compared with normal tissues, suggesting a deregulation of dendrogenin A metabolism during carcinogenesis. We established that dendrogenin A is a selective inhibitor of cholesterol epoxide hydrolase and it triggered tumour re-differentiation and growth control in mice and improved animal survival. The properties of dendrogenin A and its decreased level in tumours suggest a physiological function in maintaining cell integrity and differentiation. The discovery of dendrogenin A reveals a new metabolic pathway at the crossroads of cholesterol and histamine metabolism and the existence of steroidal alkaloids in mammals.

Redox regulation of mast cell histamine release in thioredoxin-1 (TRX) transgenic mice.

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Son, Aoi; Nakamura, Hajime; Kondo, Norihiko; Matsuo, Yoshiyuki; Liu, Wenrui; Oka, Shin-ichi; Ishii, Yasuyuki; Yodoi, Junji

2006-02-01

Thioredoxin-1 (TRX) is a stress-inducible redox-regulatory protein with antioxidative and anti-inflammatory effects. Here we show that the release of histamine from mast cells elicited by cross-linking of high-affinity receptor for IgE (FcepsilonRI) was significantly suppressed in TRX transgenic (TRX-tg) mice compared to wild type (WT) mice. Intracellular reactive oxygen species (ROS) of mast cells stimulated by IgE and antigen was also reduced in TRX-tg mice compared to WT mice. Whereas there was no difference in the production of cytokines (IL-6 and TNF-alpha) from mast cells in response to 2,4-dinitrophenylated bovine serum albumin (DNP-BSA) stimulation in TRX-tg and WT mice. Immunological status of TRX-tg mice inclined to T helper (Th) 2 dominant in primary immune response, although there was no difference in the population of dendritic cells (DCs) and regulatory T cells. We conclude that the histamine release from mast cells in TRX-tg mice is suppressed by inhibition of ROS generation. As ROS are involved in mast cell activation and facilitate mediator release, TRX may be a key signaling molecule regulating the early events in the IgE signaling in mast cells and the allergic inflammation.

Tick saliva increases production of three chemokines including monocyte chemoattractant protein-1, a histamine-releasing cytokine

Czech Academy of Sciences Publication Activity Database

Langhansová, Helena; Bopp, T.; Schmitt, E.; Kopecký, Jan

2015-01-01

Roč. 37, č. 2 (2015), s. 92-96 ISSN 0141-9838 R&D Projects: GA ČR GCP302/11/J029 Institutional support: RVO:60077344 Keywords : chemokine * histamine * Ixodes ricinus * mcp-1 * Th2 response * tick saliva Subject RIV: EC - Immunology Impact factor: 1.917, year: 2015

Increased susceptibility to diet-induced obesity in histamine-deficient mice

DEFF Research Database (Denmark)

Jørgensen, Emilie A; Vogelsang, Thomas W; Knigge, Ulrich

2006-01-01

in the development of high-fat diet (HFD)-induced obesity. METHODS: Histamine-deficient histidine decarboxylase knock-out (HDC-KO) mice and C57BL/6J wild-type (WT) mice were given either a standard diet (STD) or HFD for 8 weeks. Body weight, 24-hour caloric intake, epididymal adipose tissue size, plasma leptin...... weeks, whereas a significant difference in body weight gain was first observed after 5 weeks in WT mice. After 8 weeks 24-hour caloric intake was significantly lower in HFD- than in STD-fed WT mice. In HDC-KO mice no difference in caloric intake was observed between HFD- and STD-fed mice. After 8 weeks...

Histamine and chondroitin sulfate E proteoglycan released by cultured human colonic mucosa: indication for possible presence of E mast cells

International Nuclear Information System (INIS)

Eliakim, R.; Gilead, L.; Ligumsky, M; Okon, E.; Rachmilewitz, D.; Razin, E.

1986-01-01

An association between the release of histamine and chondroitin sulfate E proteoglycan (PG) was demonstrates in human colonic mucosa (HCM). Colonic biopsy samples incorporated [ 35 S]sulfate into PG, which was partially released into the culture medium during the incubation period. Ascending thin-layer chromatography of the released 35 S-labeled PG after its digestion by chondroitin ABC lyase (chondroitinase, EC 4.2.2.4) followed by autoradiography yielded three products that migrated in the position of monosulfated disaccharides of N-acetylgalactosamine 4-sulfate and N-acetylgalactosoamine 6-sulfate and of an oversulfated disaccharide possessing N-acetylgalatosamine 4,6-disulfate. Cultured colonic mucosa released 23.6 +/- 3.7ng of histamine per mg of wet tissue without any special trigger. Comparison by linear regression analysis of the release of histamine and chondroitin [ 35 S]sulfate E PG revealed a correlation coefficient (r) of 0.7. Histological examination of the colonic biopsies revealed the presence of many mast cells in various degrees of degranulation in the mucosa and submucosa. The above correlation, the observation that most of the mast cells showed various degrees of degranulation, and the lack of heparin synthesis as opposed to the synthesis and immunological release of chondroitin sulfate E strongly suggest that the E mast cell exists in the human colon

GABAA receptor partial agonists and antagonists

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Krall, Jacob; Balle, Thomas; Krogsgaard-Larsen, Niels

2015-01-01

to the local temporal pattern of GABA impact, enabling phasic or tonic inhibition. Specific GABAAR antagonists are essential tools for physiological and pharmacological elucidation of the different type of GABAAR inhibition. However, distinct selectivity among the receptor subtypes (populations) has been shown...... antagonists have been essential in defining the tonic current but both remaining issues concerning the GABAARs involved and the therapeutic possibilities of modulating tonic inhibition underline the need for GABAAR antagonists with improved selectivity....

The Effect of Schinus terebinthifolius Raddi (Anacardiaceae) Bark Extract on Histamine-Induced Paw Edema and Ileum Smooth Muscle Contraction.

Science.gov (United States)

Nunes-Neto, Paulo Alexandre; Peixoto-Sobrinho, Tadeu José da Silva; da Silva Júnior, Edilson Dantas; Leopoldina da Silva, Jamilka; Rodrigo da Silva Oliveira, Alisson; Pupo, André Sampaio; Araújo, Alice Valença; da Costa-Silva, João Henrique; Wanderley, Almir Gonçalves

2017-01-01

Schinus terebinthifolius Raddi (Anacardiaceae), popularly known as red aroeira, is used in traditional medicine to treat inflammatory, gastric, and respiratory disorders. The aim of this study was to evaluate the antihistaminic activity of S. terebinthifolius (St) bark extract by using in vivo and in vitro experimental models. The effects of St were investigated on contractions induced by histamine, carbachol, and potassium chloride in isolated guinea pig ileum. St was also studied in response to hind paw edema induced by histamine in rats. Experiments revealed that although St (250, 500, and 1,000  µ g/mL) reduced the histamine-induced contractions by 9.1 ± 1.8, 50.2 ± 2.0, and 68.9 ± 2.0%, respectively, it did not inhibit contractions induced by carbachol or KCl. The association of St (250 and 500  µ g/mL) with hydroxyzine, an H 1 -antihistamine (0.125 and 0.250  µ M), increased the inhibitory effect to 67.0 ± 3.2 and 85.1 ± 2.1%, respectively. Moreover, St (100, 200, and 400 mg/kg) decreased paw edema from its peak by 33.9, 48.4, and 54.8%, respectively, whereas hydroxyzine (70 mg/kg) inhibited the peak edema by 56.5%. Altogether, the results suggest that the bark extract of S. terebinthifolius has an antihistaminic effect (H 1 ).

Loss of Melanopsin Photoreception and Antagonism of the Histamine H3 Receptor by Ciproxifan Inhibit Light-Induced Sleep in Mice.

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Fanuel Muindi

Full Text Available Light has direct effects on sleep and wakefulness causing arousal in diurnal animals and sleep in nocturnal animals. In the present study, we assessed the modulation of light-induced sleep by melanopsin and the histaminergic system by exposing mice to millisecond light flashes and continuous light respectively. First, we show that the induction of sleep by millisecond light flashes is dose dependent as a function of light flash number. We found that exposure to 60 flashes of light occurring once every 60 seconds for 1-h (120-ms of total light over an hour induced a similar amount of sleep as a continuous bright light pulse. Secondly, the induction of sleep by millisecond light flashes was attenuated in the absence of melanopsin when animals were presented with flashes occurring every 60 seconds over a 3-h period beginning at ZT13. Lastly, the acute administration of a histamine H3 autoreceptor antagonist, ciproxifan, blocked the induction of sleep by a 1-h continuous light pulse during the dark period. Ciproxifan caused a decrease in NREMS delta power and an increase in theta activity during both sleep and wake periods respectively. The data suggest that some form of temporal integration occurs in response to millisecond light flashes, and that this process requires melanopsin photoreception. Furthermore, the pharmacological data suggest that the increase of histaminergic neurotransmission is sufficient to attenuate the light-induced sleep response during the dark period.

Growth, inactivation and histamine formation of Morganella psychrotolerans and Morganella morganii - development and evaluation of predictive models

DEFF Research Database (Denmark)

Emborg, Jette; Dalgaard, Paw

2008-01-01

and histamine formation by Morganella psychrotolerans. International Journal of Food Microbiology. doi:10.1016/j.ijfoodmicro.2008.08.016] Growth rates for M. psychrotolerans and M. morganii were determined at different constant temperatures from 0 degrees C to 42.5 degrees C whereas heat inactivation...

Naloxone : actions of an antagonist

NARCIS (Netherlands)

Dorp, Eveline Louise Arianna van

2009-01-01

The opioid antagonist naloxone has a special place in pharmacology – it has no intrinsic action of its own, but it is able to save lives in the case of life threatening side-effects caused by other drugs. Naloxone is an antagonist for all opioid receptors, but most specifically for the μ-opioid

Cytopathology and exocrine dysfunction induced in ex vivo rabbit lacrimal gland acinar cell models by chronic exposure to histamine or serotonin.

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McDonald, Michelle L; Wang, Yanru; Selvam, Shivaram; Nakamura, Tamako; Chow, Robert H; Schechter, Joel E; Yiu, Samuel C; Mircheff, Austin K

2009-07-01

Lacrimal immunohistopathology has diverse clinical presentations, suggesting that inflammatory mediators exert diverse influences. Chronic exposure to agonistic acetylcholine receptor autoantibodies has been studied previously; the present work addressed mediators that signal through other G protein-coupled receptors. Acinus-like structures and reconstituted acinar epithelial monolayers from rabbit lacrimal glands were exposed to varying concentrations of histamine or 5-hydroxytryptamine (5-HT) for 20 hours. Net and vectorial beta-hexosaminidase secretion, cytosolic Ca(2+) (Ca(i)) elevation, apical recruitment of p150(Glued), actin microfilament meshwork organization, and ultrastructure were assessed. Histamine and 5-HT acutely stimulated beta-hexosaminidase secretion at lower, but not higher, concentrations. Neither of them acutely elevated Ca(i) levels. Both recruited p150(Glued) at concentrations that failed to induce secretion. Chronic exposure to 10 mM histamine inhibited carbachol (CCh)-induced beta-hexosaminidase secretion and prevented the formation of continuous monolayers; 1 mM 5-HT partially inhibited secretion at the apical medium. Neither altered secretion to the basal medium. Chronic exposure to histamine or 5-HT partially decreased CCh induced Ca(i) elevations and p150(Glued) recruitment, even at concentrations that did not inhibit secretion. Both expanded acinar lumina and thickened microfilament meshworks, and both caused homotypic fusion of secretory vesicles and formation of aqueous vacuoles in the apical and basal cytoplasm. Chronic exposure to forskolin, which activates adenylyl cyclase, induced similar cytopathologic changes but impaired secretion modestly and only at the highest concentration tested. Inflammatory mediators that signal through G protein-coupled receptors cause acinar cell cytopathology and dose-dependent reductions of CCh-induced beta-hexosaminidase secretion. Although agonistic acetylcholine receptor autoantibodies may cause

Histamine H3 receptor ligands in the group of (homo)piperazine derivatives.

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Szczepanska, Katarzyna; Kuder, Kamil; Kiec-Kononowicz, Katarzyna

2017-11-23

Since its' discovery in 1983, followed by gene cloning in 1999, the histamine H3 receptor served as an outstanding target for drug discovery. The wide spectrum of possible therapeutic implications make H3R's one of the most researched areas in the vast GPCR ligands field - started from imidazole containing ligands, through various successful imidazole replacements, with recent introduction of Wakix® to pharmaceutical market. One of such replacements is piperazine moiety, a significant versatile scaffold in rational drug design for most of the GPCR ligands. Therefore, herein we review ligands built on piperazine, as well as its seven membered analogue azepine, that target H3R's and their potential therapeutical applications, in order to elucidate the current state of the art in this vast field. Due to a high level of structural divergence among compounds described herein, we decided to divide them into groups, where the key division element was the position of nitrogen basicity decreasing moieties in (homo)piperazine ring. Paying attention to a number of published structures and their overall high biological activity, one can realize that the (homo)piperazine scaffold bids a versatile template also for histamine H3 receptor ligands. With two possible substitution sites and therefore a number of possible structural combinations, piperazine derivatives stand as one of the largest group of high importance among H3R ligands. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Pneumonia prevention in intubated patients given sucralfate versus proton-pump inhibitors and/or histamine II receptor blockers.

Science.gov (United States)

Grindlinger, Gene A; Cairo, Sarah B; Duperre, Carole B

2016-12-01

Ventilator-associated pneumonia (VAP) is a common cause of infectious morbidity and mortality in the intensive care unit (ICU). The type of stress-ulcer prophylaxis (SUP) given to ventilated patients may, in part, be responsible. We observed an increase in VAP as ventilator bundle compliance increased and a decrease in VAP when bundle compliance decreased. We reasoned that SUP which raises gastric pH such as proton-pump inhibitors (PPIs) and histamine II (H2) receptor antagonists as opposed to SUP which does not raise pH such as sucralfate (S) may be responsible and also may alter the causative bacteria. This is a single-center retrospective cohort analysis of all intubated, adult surgical patients admitted to the surgical ICU between January and June during the 3-y period 2012-2014. Demographics, APACHE II, Injury Severity Score, VAP occurrence, culprit bacteria, ventilator days, and ICU days were recorded based on the type of SUP given. There were 45 instances of VAP in the 504 study patients, 33 in the PPI/H2 group, and 12 in the S group (P < 0.01). VAP per 1000 ventilator days were 10.2 for PPI/H2 and 3.7 for S (P < 0.01). Culprit bacteria were mostly Pseudomonas, gram-negative bacilli, and methicillin-resistant Staphylococcus aureus in PPI/H2 patients (n = 29) compared with oropharyngeal flora in S patients (n = 6; P < 0.001). There was a substantial difference in VAP occurrence and in the culprit bacteria between S and PPI/H2 treated patients due perhaps to gastric alkalization. Copyright © 2016 Elsevier Inc. All rights reserved.

Role of Histamine Release Test for the Evaluation of Patients with Immediate Hypersensitivity Reactions to Clavulanic Acid

DEFF Research Database (Denmark)

Pineda, F.; Ariza, A.; Mayorga, C.

2015-01-01

Immediate hypersensitivity reactions to clavulanic acid (CLV) seem to be on the increase. Diagnosis is mainly based on skin testing and the drug provocation test (DPT), procedures that are not risk free. The aim of this study was to evaluate whether the histamine release test (HRT) could help eva...

Large-scale overproduction, functional purification and ligand affinities of the His-tagged human histamine H1 receptor.

NARCIS (Netherlands)

Ratnala, V.R.; Swarts, H.G.P.; Oostrum, J. van; Leurs, R.; Groot, H.J.M. de; Bakker, R.; Grip, W.J. de

2004-01-01

This report describes an efficient strategy for amplified functional purification of the human H1 receptor after heterologous expression in Sf9 cells. The cDNA encoding a C-terminally histidine-tagged (10xHis) human histamine H1 receptor was used to generate recombinant baculovirus in a Spodoptera

Involvement of prostaglandins and histamine in nickel wire-induced acute inflammation in mice.

Science.gov (United States)

Hirasawa, Noriyasu; Goi, Yoshiaki; Tanaka, Rina; Ishihara, Kenji; Ohtsu, Hiroshi; Ohuchi, Kazuo

2010-06-15

The irritancy of Nickel (Ni) ions has been well documented clinically. However, the chemical mediators involved in the acute inflammation induced by solid Ni are not fully understood. We used the Ni wire-implantation model in mice and examined roles of prostaglandins and histamine in plasma leakage in the acute phase. The subcutaneous implantation of a Ni wire into the back of mice induced plasma leakage from 8 to 24 h and tissue necrosis around the wire at 3 days, whereas the implantation of an aluminum wire induced no such inflammatory responses. An increase in the mRNA for cyclooxygenase (COX)-2 and HDC in cells around the Ni wire was detected 4 h after the implantation. The leakage of plasma at 8 h was inhibited by indomethacin in a dose-dependent manner. Dexamethasone and the p38 MAP kinase inhibitor SB203580 also inhibited the exudation of plasma consistent with the inhibition of the expression of COX-2 mRNA. Furthermore, plasma leakage was partially but siginificantly reduced in histamine H1 receptor knockout mice and histidine decarboxylase (HDC) knockout mice but not in H2 receptor knockout mice. These results suggested that the Ni ions released from the wire induced the expression of COX-2 and HDC, resulting in an increase in vascular permeability during the acute phase of inflammation. (c) 2009 Wiley Periodicals, Inc.

Sum frequency generation (SFG) vibrational spectroscopy of planar phosphatidylethanolamine hybrid bilayer membranes under water.

Science.gov (United States)

Kett, Peter J N; Casford, Michael T L; Davies, Paul B

2010-06-15

Sum frequency generation (SFG) spectroscopy has been used to study the structure of phosphatidylethanolamine hybrid bilayer membranes (HBMs) under water at ambient temperatures. The HBMs were formed using a modified Langmuir-Schaefer technique and consisted of a layer of dipalmitoyl phosphatidylethanolamine (DPPE) physisorbed onto an octadecanethiol (ODT) self-assembled monolayer (SAM) at a series of surface pressures from 1 to 40 mN m(-1). The DPPE and ODT were selectively deuterated so that the contributions to the SFG spectra from the two layers could be determined separately. SFG spectra in both the C-H and C-D stretching regions confirmed that a monolayer of DPPE had been adsorbed to the ODT SAM and that there were gauche defects within the alkyl chains of the phospholipid. On adsorption of a layer of DPPE, methylene modes from the ODT SAM were detected, indicating that the phospholipid had partially disordered the alkanethiol monolayer. SFG spectra recorded in air indicated that removal of water from the surface of the HBM resulted in disruption of the DPPE layer and the formation of phospholipid bilayers.

575 Photoaging Attenuates Skin Test Response to Histamine More Than Natural Aging

OpenAIRE

King, Monroe James; Fitzhugh, David; Lockey, Richard F.

2012-01-01

Background Clinical experience suggests that skin test reactivity is often decreased in photo-exposed skin versus sun-protected skin in older individuals. The current study was designed to address whether photoaging or natural aging of skin causes a greater diminution in skin test reponse. Methods Prick-puncture skin tests to histamine were performed on sun-exposed and sun-protected areas in younger (n = 61, age 20–50) and older (n = 63, age 60–87) adult volunteers who were recruited for skin...

Effect of amiloride on arachidonic acid and histamine release from rat mast cells

DEFF Research Database (Denmark)

Linnebjerg, H.; Hansen, Harald S.; Jensen, B.

1989-01-01

The effect of a putative Na/H exchange inhibition on histamine and [C]arachidonic acid ([C]AA) release has been examined in rat peritoneal mast cells, using either addition of amiloride or removal of extracellular Na. The cells were stimulated by non-immunological agents, i.e. calcium ionophore A......23187, nerve growth factor (NGF), thapsigargin and compound 48/80. On the basis of the results obtained, a possible role for Na/H exchange in rat mast cell secretion is discussed....

Sequencing and transcriptional analysis of the Streptococcus thermophilus histamine biosynthesis gene cluster: factors that affect differential hdcA expression

DEFF Research Database (Denmark)

Calles-Enríquez, Marina; Hjort, Benjamin Benn; Andersen, Pia Skov

2010-01-01

to produce histamine. The hdc clusters of S. thermophilus CHCC1524 and CHCC6483 were sequenced, and the factors that affect histamine biosynthesis and histidine-decarboxylating gene (hdcA) expression were studied. The hdc cluster began with the hdcA gene, was followed by a transporter (hdcP), and ended...... with the hdcB gene, which is of unknown function. The three genes were orientated in the same direction. The genetic organization of the hdc cluster showed a unique organization among the lactic acid bacterial group and resembled those of Staphylococcus and Clostridium species, thus indicating possible...... acquisition through a horizontal transfer mechanism. Transcriptional analysis of the hdc cluster revealed the existence of a polycistronic mRNA covering the three genes. The histidine-decarboxylating gene (hdcA) of S. thermophilus demonstrated maximum expression during the stationary growth phase, with high...

Coordination studies of 1,2-bis(diphenylphosphinoethane with di-μ-hydroxo dinuclear complexes of tungsten(IV and molybdenum(IV

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Minato Makoto

2016-01-01

Full Text Available The new trifluoroethoxo phosphine complexes [Cp2M(η1-dppe(CF3CH2O]+ and [Cp2(CF3CH2OM(μ-dppeMCp2(CF3CH2O]2+ (M = Mo or W, Cp = η-C5H5 and dppe = Ph2PCH2CH2PPh2 have been prepared by reaction of cationic di-μ-hydroxo dinuclear complex of molybdenocene or tungstenocene [Cp2M(μ-OH2MCp2]2+ with dppe. From the 1H and 31P NMR data, the configurations of the products could be assigned. Furtheremore, X-ray crystallography was used to definitively identify one of the product [Cp2(CF3CH2OMo(μ-dppeMoCp2(CF3CH2O]2+, which crystallizes in space group P21/c(#14 with a = 12.230(5 Å, b = 11.149(5 Å, c = 28.966(7 Å, β = 101.07(3°, V = 3876(2 Å3, and Z = 2. It was ascertained that the amount of dppe added to the reaction mixture could influence the product distribution. A mechanism involving initial replacement of the hydroxo ligand by the alkoxo group followed by nucleophilic attack of the phosphine is proposed on the basis of the reaction profile.

Influence of MRI contrast media on histamine release from mast cells.

Science.gov (United States)

Kun, Tomasz; Jakubowski, Lucjusz

2012-07-01

Mast cells, owing to diversity of secreted mediators, play a crucial role in the regulation of inflammatory response. Together with basophils, mast cells constitute a central pathogenetic element of anaphylactic (IgE-dependent) and anaphylactoid (IgE-independent) reactions. In severe cases, generalized degranulation of mast cells may cause symptoms of anaphylactic shock. The influence of the classical, iodine-based contrast media on mastocyte degranulation has been fully described. Our objective was to determine the influence of the gadolinium-based MRI contrast media on histamine release from mast cells and to compare the activity of ionic and non-ionic preparations of contrast media. To determine the intensity of mast cell degranulation, we used an experimental model based on mastocytes isolated from rat peritoneal fluid. Purified suspensions of mast cells were incubated with various concentrations of Gd-DTPA and Gd-DTPA-BMA, and solutions of PEG 600 which served as a non-toxic osmotic stimulus. The intensity of mast cell activation was presented as mean percentage of histamine released from cells after incubation. The obtained results demonstrate that both ionic and non-ionic preparations of the MRI contrast media are able to induce mast cell degranulation in vitro. It was also proved that the non-ionic MRI contrast media stimulate mast cells markedly more weakly than ionic contrast media at identical concentration. The aforementioned results may suggest a more profitable safety profile of the non-ionic contrast preparations. We may also conclude that triggering of mast cell degranulation after incubation with the solutions of MRI contrast media results from non-specific osmotic stimulation and direct toxicity of free ionic residues.

Influence of MRI contrast media on histamine release from mast cells

International Nuclear Information System (INIS)

Kun, Tomasz; Jakubowski, Lucjusz

2012-01-01

Mast cells, owing to diversity of secreted mediators, play a crucial role in the regulation of inflammatory response. Together with basophils, mast cells constitute a central pathogenetic element of anaphylactic (IgE-dependent) and anaphylactoid (IgE-independent) reactions. In severe cases, generalized degranulation of mast cells may cause symptoms of anaphylactic shock. The influence of the classical, iodine-based contrast media on mastocyte degranulation has been fully described. Our objective was to determine the influence of the gadolinium-based MRI contrast media on histamine release from mast cells and to compare the activity of ionic and non-ionic preparations of contrast media. To determine the intensity of mast cell degranulation, we used an experimental model based on mastocytes isolated from rat peritoneal fluid. Purified suspensions of mast cells were incubated with various concentrations of Gd-DTPA and Gd-DTPA-BMA, and solutions of PEG 600 which served as a non-toxic osmotic stimulus. The intensity of mast cell activation was presented as mean percentage of histamine released from cells after incubation. The obtained results demonstrate that both ionic and non-ionic preparations of the MRI contrast media are able to induce mast cell degranulation in vitro. It was also proved that the non-ionic MRI contrast media stimulate mast cells markedly more weakly than ionic contrast media at identical concentration. The aforementioned results may suggest a more profitable safety profile of the non-ionic contrast preparations. We may also conclude that triggering of mast cell degranulation after incubation with the solutions of MRI contrast media results from non-specific osmotic stimulation and direct toxicity of free ionic residues

Human, recombinant interleukin-2 induces in vitro histamine release in a dose-dependent manner

DEFF Research Database (Denmark)

Nielsen, Hans Jørgen; Petersen, L J; Skov, P S

1995-01-01

significantly in the supernatant from cells stimulated by rIL-2 in a dose-dependent manner both in patients and volunteers. Total cell-bound histamine was 49.3 +/- 4.1 ng/ml in patients compared to 78.5 +/- 7.7 ng/ml in volunteers (p ... was significantly enhanced in cancer patients compared to volunteers (*p manner in both cancer patients and volunteers. This may in part explain the severe toxicity observed during high...

Economic evaluation of tramadol/paracetamol combination tablets for osteoarthritis pain in the Netherlands

NARCIS (Netherlands)

H. Liedgens (Hiltrud); M.J.C. Nuijten (Mark); B.P. Nautrup (Barbara Poulsen)

2005-01-01

textabstractObjective: To compare the costs of treating osteoarthritis (OA) pain using combination tramadol/paracetamol tablets, NSAIDs alone, NSAIDs plus proton pump inhibitors (PPIs), or NSAIDs plus histamine H2-receptor antagonists (H2RAs) from the perspective of the Dutch healthcare system.

Activation of the Na+/K(+)-pump in rat peritoneal mast cells following histamine release: a possible role in cell recovery

DEFF Research Database (Denmark)

Knudsen, T; Ferjan, I; Johansen, Torben

1993-01-01

1. The activity of the Na+/K(+)-pump in rat peritoneal mast cells was measured at various time intervals after induction of cellular histamine release by compound 48/80 or by the antigen-antibody reaction. The Na+/K(+)-pump activity was assessed as the ouabain-sensitive potassium uptake....... On the basis of the present results, we suggest a role for the Na+/K(+)-pump in the recovery process of the mast cell following histamine release....... of the cells using 86Rb+ as a tracer for potassium (K+(86Rb+)-uptake). 2. Stimulation of the cells with compound 48/80 induced a time and concentration dependent increase of the Na+/K(+)-pump activity. The pump activity was maximal 2 min after stimulation of the cells. Then, the activity gradually decreased...

Effect of high-voltage electrical stimulation on the albumin and histamine serum concentrations, edema, and pain in acute joint inflammation of rats

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Maria C. Sandoval

2015-04-01

Full Text Available BACKGROUND: The mechanism by which high-voltage electrical stimulation (HVPC acts on edema reduction is unknown. OBJECTIVE: To assess the effect of HVPC with negative polarity (- applied to the ankle of rats with acute joint inflammation. METHOD: Sixty-four rats were divided into four groups (n=16: inflamed+HVPC(-, 0.03 mL application of ι-carrageenan (3% to the tibiotarsal joint plus HVPC(-; inflamed+HVPC placebo, carrageenan application and HVPC placebo; normal+HVPC(-, HVPC application(-; and normal control, no intervention. The HVPC(- 100 Hz at a submotor level was applied daily for 45 min on three consecutive days. The variables were pain, hind-foot volume, and serum histamine and albumin assessed before and during the 48 hours following inflammation. The variables were compared using the t test, one-way ANOVA, nested ANOVA for repeated measures, and the post hoc Bonferroni test. Analysis of covariance was applied to adjust the effects of HVPC(- by measurements of pain, inflammation, albumin, and histamine at 24 h, and the final weight was compared to the other groups. The significance level was set at p0.05. Albumin was reduced in the groups that received the intervention, but there was no differences between them. There was only a 24 hour increase in histamine with the normal+HVPC(- (p=0.0001 and inflamed+HVPC placebo groups (p=0.01 compared to the normal control group. CONCLUSIONS: The results of the present study suggest that HVPC(- with the parameters employed did not reduce pain or edema and did not change serum albumin or histamine levels,, which indicates the inability of this resource to have a positive effect when treating treat acute joint inflammation.

A search for presynaptic inhibitory histamine receptors in guinea-pig tissues: Further H3 receptors but no evidence for H4 receptors.

Science.gov (United States)

Petri, Doris; Schlicker, Eberhard

2016-07-01

The histamine H4 receptor is coupled to Gi/o proteins and expressed on inflammatory cells and lymphoid tissues; it was suggested that this receptor also occurs in the brain or on peripheral neurones. Since many Gi/o protein-coupled receptors, including the H3 receptor, serve as presynaptic inhibitory receptors, we studied whether the sympathetic neurones supplying four peripheral tissues and the cholinergic neurones in the hippocampus from the guinea-pig are equipped with release-modulating H4 and H3 receptors. For this purpose, we preincubated tissue pieces from the aorta, atrium, renal cortex and vas deferens with (3)H-noradrenaline and hippocampal slices with (3)H-choline and determined the electrically evoked tritium overflow. The stimulation-evoked overflow in the five superfused tissues was inhibited by the muscarinic receptor agonist oxotremorine, which served as a positive control, but not affected by the H4 receptor agonist 4-methylhistamine. The H3 receptor agonist R-α-methylhistamine inhibited noradrenaline release in the peripheral tissues without affecting acetylcholine release in the hippocampal slices. Thioperamide shifted the concentration-response curve of histamine in the aorta and the renal cortex to the right, yielding apparent pA2 values of 8.0 and 8.1, respectively, which are close to its affinity at other H3 receptors but higher by one log unit than its pKi at the H4 receptor of the guinea-pig. In conclusion, histamine H4 receptors could not be identified in five experimental models of the guinea-pig that are suited for the detection of presynaptic inhibitory receptors whereas H3 receptors could be shown in the peripheral tissues but not in the hippocampus. This article is part of the Special Issue entitled 'Histamine Receptors'. Copyright © 2015 Elsevier Ltd. All rights reserved.

[μ-1,2-Bis(diphenylphosphinoethane-κ2P:P′]bis{[1,2-bis(diphenylphosphinoethane-κ2P,P′]cyanidocopper(I} methanol disolvate

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Rong Wang

2010-08-01

Full Text Available The title centrosymmetric complex, [Cu2(CN2(C26H24P23]·2CH3OH, consists of two five-membered [Cu(dppeCN] rings [dppe is 1,2-bis(diphenylphosphinoethane] bridged by one μ2-dppe ligand, and two methanol solvent molecules. The angles around the central metal atom indicate that each CuI atom is located in the center of a distorted tetrahedron. The coordination sphere of each CuI atom is formed by three P atoms from two dppe ligands, and one C atom from the cyanide ligand. The crystal structure is stabilized by O—H...N hydrogen bonds, which are formed by the O—H donor group from methanol and the N-atom acceptor from a cyanide ligand.

Pharmacologic study of calcium influx pathways in rabbit aortic smooth muscle

International Nuclear Information System (INIS)

Lukeman, D.S.

1987-01-01

Functional characteristics and pharmacologic domains of receptor-operated and potential-sensitive calcium (Ca 2+ ) channels (ROCs and PSCs, respectively) were derived via measurements of 45 Ca 2+ influx (M/sup Ca/) during activation by the neurotransmitters norepinephrine (NE), histamine (HS), and serotonin (5-HT) and by elevated extracellular potassium (K + ) in the individual or combined presence of organic Ca 2+ channel antagonists (CAts), calmodulin antagonists (Calm-ants), lanthanum (La 3+ ), and agents that increase intracellular levels of cyclic AMP

2) 胃・十二指腸潰瘍の薬物療法(シンポジウム 食道・胃・十二指腸潰瘍の薬物療法, 第416回新潟医学会)

OpenAIRE

杉山, 一教; 富所, 隆; Sugiyama, Kazunori; Tomidokoro, Takashi

1988-01-01

Therapy of gastric and duodenal ulcers has achieved a striking progress of the appearance of muscarin receptor antagonist (pirenzepine) and histamine H_2-receptor antagonist (H_2-blocker). Especially disappearance of subjective symptoms and promotion of cure achieved by these drugs are widely well-appreciated. On the other hand, with the acumulation of use experience of the drugs, much attention is being paid to the importance of early recurrence and maintenance therapy. At this point, attent...

Stimulation of phospholipase C in cultured microvascular endothelial cells from human frontal lobe by histamine, endothelin and purinoceptor agonists.

Science.gov (United States)

Purkiss, J. R.; West, D.; Wilkes, L. C.; Scott, C.; Yarrow, P.; Wilkinson, G. F.; Boarder, M. R.

1994-01-01

1. Cultures of endothelial cells derived from the microvasculature of human frontal lobe have been investigated for phospholipase C (PLC) responses to histamine, endothelins and purinoceptor agonists. 2. Using cells prelabelled with [3H]-inositol and measuring total [3H]-inositol (poly)phosphates, histamine acting at H1 receptors stimulated a substantial response with an EC50 of about 10 microM. 3. Endothelin-1 also gave a clear stimulation of phosphoinositide-specific phospholipase C. Both concentration-response curves and binding curves showed effective responses and binding in the rank order of endothelin-1 > sarafotoxin S6b > endothelin-3, suggesting an ETA receptor. 4. Assay of total [3H]-inositol (poly)phosphates showed no response to the purinoceptor agonists, 2-methylthioadenosine 5'-trisphosphate (2MeSATP), adenosine 5'-O-(3-thiotrisphosphate) (ATP gamma S) or beta,gamma-methylene ATP. Both ATP and UTP gave a small PLC response. 5. Similarly, when formation of [32P]-phosphatidic acid from cells prelabelled with 32Pi was used as an index of both PLC and phospholipase D, a small response to ATP and UTP was seen but there was no response to the other purinoceptor agonists tested. 6. Study by mass assay of stimulation by ATP of inositol (1,4,5) trisphosphate accumulation revealed a transient response in the first few seconds, a decline to basal, followed by a small sustained response. 7. These results show that human brain endothelial cells in culture are responsive to histamine and endothelins in a manner which may regulate brain capillary permeability. Purines exert a lesser influence. PMID:8032588

Adverse cutaneous reactions induced by TNF-alpha antagonist therapy.

Science.gov (United States)

Borrás-Blasco, Joaquín; Navarro-Ruiz, Andrés; Borrás, Consuelo; Casterá, Elvira

2009-11-01

To review adverse cutaneous drug reactions induced by tumor necrosis factor alpha (TNF-alpha) antagonist therapy. A literature search was performed using PubMed (1996-March 2009), EMBASE, and selected MEDLINE Ovid bibliography searches. All language clinical trial data, case reports, letters, and review articles identified from the data sources were used. Since the introduction of TNF-alpha antagonist, the incidence of adverse cutaneous drug reactions has increased significantly. A wide range of different skin lesions might occur during TNF-alpha antagonist treatment. New onset or exacerbation of psoriasis has been reported in patients treated with TNF-alpha antagonists for a variety of rheumatologic conditions. TNF-alpha antagonist therapy has been associated with a lupus-like syndrome; most of these case reports occurred in patients receiving either etanercept or infliximab. Serious skin reactions such as erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported rarely with the use of TNF-alpha antagonists. As the use of TNF-alpha antagonists continues to increase, the diagnosis and management of cutaneous side effects will become an increasingly important challenge. In patients receiving TNF-alpha antagonist treatment, skin disease should be considered, and clinicians need to be aware of the adverse reactions of these drugs.

Mutations in the histamine N-methyltransferase gene, HNMT, are associated with nonsyndromic autosomal recessive intellectual disability

Science.gov (United States)

Heidari, Abolfazl; Tongsook, Chanakan; Najafipour, Reza; Musante, Luciana; Vasli, Nasim; Garshasbi, Masoud; Hu, Hao; Mittal, Kirti; McNaughton, Amy J. M.; Sritharan, Kumudesh; Hudson, Melissa; Stehr, Henning; Talebi, Saeid; Moradi, Mohammad; Darvish, Hossein; Arshad Rafiq, Muhammad; Mozhdehipanah, Hossein; Rashidinejad, Ali; Samiei, Shahram; Ghadami, Mohsen; Windpassinger, Christian; Gillessen-Kaesbach, Gabriele; Tzschach, Andreas; Ahmed, Iltaf; Mikhailov, Anna; Stavropoulos, D. James; Carter, Melissa T.; Keshavarz, Soraya; Ayub, Muhammad; Najmabadi, Hossein; Liu, Xudong; Ropers, Hans Hilger; Macheroux, Peter; Vincent, John B.

2015-01-01

Histamine (HA) acts as a neurotransmitter in the brain, which participates in the regulation of many biological processes including inflammation, gastric acid secretion and neuromodulation. The enzyme histamine N-methyltransferase (HNMT) inactivates HA by transferring a methyl group from S-adenosyl-l-methionine to HA, and is the only well-known pathway for termination of neurotransmission actions of HA in mammalian central nervous system. We performed autozygosity mapping followed by targeted exome sequencing and identified two homozygous HNMT alterations, p.Gly60Asp and p.Leu208Pro, in patients affected with nonsyndromic autosomal recessive intellectual disability from two unrelated consanguineous families of Turkish and Kurdish ancestry, respectively. We verified the complete absence of a functional HNMT in patients using in vitro toxicology assay. Using mutant and wild-type DNA constructs as well as in silico protein modeling, we confirmed that p.Gly60Asp disrupts the enzymatic activity of the protein, and that p.Leu208Pro results in reduced protein stability, resulting in decreased HA inactivation. Our results highlight the importance of inclusion of HNMT for genetic testing of individuals presenting with intellectual disability. PMID:26206890

Histamine formation and the freshness of yellowfin tuna (Thunnus albacares stored at different temperatures

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B.K.K.K. Jinadasa

2015-12-01

Full Text Available This study was conducted to investigate the effect of storage temperatures on the shelf life of yellowfin tuna (YFT loins by studying of microbial, chemical and organoleptic changes. Shelf life of YFT was determined through changes in total aerobic bacterial plate counts (APC, total volatile basic nitrogen (TVB-N trimethylamine (TMA, organoleptic properties and histamine development during storage at 0, 4 and 7°C. Based on TVB-N value indices, YFT maintained an acceptable shelf life for 21, 17 and 12 days at 0, 4 and 7°C, respectively. Nevertheless, YFT was rejected earlier by the sensory panellists than their TVB-N value indicated. Histamine development was found to be lower than the European Union safety level for 100 mg/kg fish during storage at 0 and 7°C for 21 and 17 days, respectively. Aerobic bacteria initially dominated the micro-flora on YFT; however, as storage time increased, aerobic bacteria became dominant at cold storage, but the numbers exceeded the International Commission on Microbiological Specifications for Foods (ICMSF limit of 107 cfu/g in storage at 7°C after 17 days. Therefore, it can be concluded that the storage of fresh YFT in below 4°C has good enough to the shelf life of products (two weeks.

Behavior of lysozyme adsorbed onto biological liquid crystal lipid monolayer at the air/water interface

Science.gov (United States)

Lu, Xiaolong; Shi, Ruixin; Hao, Changchun; Chen, Huan; Zhang, Lei; Li, Junhua; Xu, Guoqing; Sun, Runguang

2016-09-01

The interaction between proteins and lipids is one of the basic problems of modern biochemistry and biophysics. The purpose of this study is to compare the penetration degree of lysozyme into 1,2-diapalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphoethano-lamine (DPPE) by analyzing the data of surface pressure-area (π-A) isotherms and surface pressure-time (π-T) curves. Lysozyme can penetrate into both DPPC and DPPE monolayers because of the increase of surface pressure at an initial pressure of 15 mN/m. However, the changes of DPPE are larger than DPPC, indicating stronger interaction of lysozyme with DPPE than DPPC. The reason may be due to the different head groups and phase state of DPPC and DPPE monolayers at the surface pressure of 15 mN/m. Atomic force microscopy reveals that lysozyme was absorbed by DPPC and DPPE monolayers, which leads to self-aggregation and self-assembly, forming irregular multimers and conical multimeric. Through analysis, we think that the process of polymer formation is similar to the aggregation mechanism of amyloid fibers. Project supported by the National Natural Science Foundation of China (Grant Nos. 21402114 and 11544009), the Natural Science Basic Research Plan in Shaanxi Province of China (Grant No. 2016JM2010), the Fundamental Research Funds for the Central Universities of China (Grant No. GK201603026), and the National University Science and Technology Innovation Project of China (Grant No. 201610718013).

Starch source in high concentrate rations does not affect rumen pH, histamine and lipopolysaccharide concentrations in dairy cows

NARCIS (Netherlands)

Pilachai, R.; Schonewille, J.T.; Thamrongyoswittayakul, C.; Aiumlamai, S.; Wachirapakom, C.; Everts, H.; Hendriks, W.H.

2012-01-01

The replacement of ground corn by cassava meal on rumen pH, lipopolysaccharide (LPS) and histamine concentrations under typical Thai feeding conditions (high concentrate diets and rice straw as the sole source of roughage) was investigated. Four rumen-fistulated crossbred Holstein, non-pregnant, dry

Adenosine triphosphate levels during anaphylactic histamine release in rat mast cells in vitro. Effects of glycolytic and respiratory inhibitors

DEFF Research Database (Denmark)

Johansen, Torben

1979-01-01

The adenosine triphosphate (ATP) content of rat mast cells was studied during and after anaphylactic histamine release. The almost identical time course of ATP decrease from mast cells treated with either glycolytic or respiratory inhibitors supports the view that the ATP depletion was largely re...

11C-labeled and 18F-labeled PET ligands for subtype-specific imaging of histamine receptors in the brain

NARCIS (Netherlands)

Funke, U.; Vugts, D.J.; Janssen, B.; Spaans, A.; Kruijer, P.S.; Lammertsma, A.A.; Perk, L.R.; Windhorst, A.D.

2013-01-01

The signaling molecule histamine plays a key role in the mediation of immune reactions, in gastric secretion, and in the sensory system. In addition, it has an important function as a neurotransmitter in the central nervous system, acting in pituitary hormone secretion, wakefulness, motor and

Leucine 208 in human histamine N-methyltransferase emerges as a hotspot for protein stability rationalizing the role of the L208P variant in intellectual disability.

Science.gov (United States)

Tongsook, Chanakan; Niederhauser, Johannes; Kronegger, Elena; Straganz, Grit; Macheroux, Peter

2017-01-01

The degradation of histamine catalyzed by the SAM-dependent histamine N-methyltransferase (HNMT) is critically important for the maintenance of neurological processes. Recently, two mutations in the encoding human gene were reported to give rise to dysfunctional protein variants (G60D and L208P) leading to intellectual disability. In the present study, we have expressed eight L208 variants with either apolar (L208F and L208V), polar (L208N and L208T) or charged (L208D, L208H, L208K and L208R) amino acids to define the impact of side chain variations on protein structure and function. We found that the variants L208N, L208T, L208D and L208H were severely compromised in their stability. The other four variants were obtained in lower amounts in the order wild-type HNMT>L208F=L208V>L208K=L208R. Biochemical characterization of the two variants L208F and L208V exhibited similar Michaelis-Menten parameters for SAM and histamine while the enzymatic activity was reduced to 21% and 48%, respectively. A substantial loss of enzymatic activity and binding affinity for histamine was seen for the L208K and L208R variants. Similarly the thermal stability for the latter variants was reduced by 8 and 13°C, respectively. These findings demonstrate that position 208 is extremely sensitive to side chain variations and even conservative replacements affect enzymatic function. Molecular dynamics simulations showed that amino acid replacements in position 208 perturb the helical character and disrupt interactions with the adjacent β-strand, which is involved in the binding and correct positioning of histamine. This finding rationalizes the gradual loss of enzymatic activity observed in the L208 variants. Copyright © 2016 The Author(s). Published by Elsevier B.V. All rights reserved.

Small molecule antagonists of integrin receptors.

Science.gov (United States)

Perdih, A; Dolenc, M Sollner

2010-01-01

The complex and widespread family of integrin receptors is involved in numerous physiological processes, such as tissue remodeling, angiogenesis, development of the immune response and homeostasis. In addition, their key role has been elucidated in important pathological disorders such as cancer, cardiovascular diseases, osteoporosis, autoimmune and inflammatory diseases and in the pathogenesis of infectious diseases, making them highly important targets for modern drug design campaigns. In this review we seek to present a concise overview of the small molecule antagonists of this diverse and highly complex receptor family. Integrin antagonists are classified according to the targeted integrin receptor and are discussed in four sections. First we present the fibrinogen alpha(IIb)beta3 and the vitronectin alpha (V)beta(3) receptor antagonists. The remaining selective integrin antagonists are examined in the third section. The final section is dedicated to molecules with dual or multiple integrin activity. In addition, the use of antibodies and peptidomimetic approaches to modulate the integrin receptors are discussed, as well providing the reader with an overall appreciation of the field.

Gonadotrophin releasing hormone antagonist in IVF/ICSI

Directory of Open Access Journals (Sweden)

M S Kamath

2008-01-01

Full Text Available Objective : To study the efficacy of gonadotrophin releasing hormone (GnRH antagonist in In-vitro-fertilization/Intracytoplasmic sperm injection (IVF/ICSI cycles. Type of Study : Observational study. Setting: Reproductive Medicine Unit, Christian Medical College Hospital, Vellore, Tamil Nadu. Materials and Methods: GnRH antagonists were introduced into our practice in November 2005. Fifty-two women undergoing the antagonist protocol were studied and information gathered regarding patient profile, treatment parameters (total gonadotrophin dosage, duration of treatment, and oocyte yield, and outcomes in terms of embryological parameters (cleavage rates, implantation rates and clinical pregnancy. These parameters were compared with 121 women undergoing the standard long protocol. The costs between the two groups were also compared. Main Outcome : Clinical pregnancy rate. Results : The clinical pregnancy rate per embryo transfer in the antagonist group was 31.7% which was comparable to the clinical pregnancy rate in women undergoing the standard long protocol (30.63%. The costs between the two groups were comparable. Conclusions : GnRH antagonist protocol was found to be effective and comparable to the standard long protocol regimen. In addition it was simple, convenient, and patient friendly.

History of the 'geste antagoniste' sign in cervical dystonia.

Science.gov (United States)

Poisson, A; Krack, P; Thobois, S; Loiraud, C; Serra, G; Vial, C; Broussolle, E

2012-08-01

The geste antagoniste is a voluntary maneuver that temporarily reduces the severity of dystonic posture or movements. It is a classical feature of focal and particularly cervical dystonia. However, the precise historical aspects of geste antagoniste still remain obscure. The goals of this review were (1) to clarify the origin of the geste antagoniste sign; (2) to identify the factors that led to its diffusion in the international literature; (3) to follow the evolution of that term across the twentieth century. We used medical and neurological French, German and English literature of the late nineteenth and early twentieth centuries, and the PubMed database by entering the terms geste antagoniste, antagonistic gesture and sensory trick. The geste antagoniste sign is a legacy of the Paris Neurological School of the end of the nineteenth century. The term was introduced by Meige and Feindel in their 1902 book on tics, written in the vein of their master, Brissaud, who first described this sign in 1893. The almost immediate translations of this book by Giese into German and Kinnier Wilson into English contributed to the rapid spreading of the term geste antagoniste, which is still in use worldwide today. The term antagonistic gesture is the translation proposed by Kinnier Wilson, which also led to the use of the term geste antagonistique. The geste antagoniste sign has long been considered a solid argument for the psychogenic origins of dystonia until the 1980s when Marsden made strong arguments for its organic nature.

The effects of high levels of rumen degradable protein on rumen pH and histamine concentrations in dairy cows

NARCIS (Netherlands)

Pilachai, R.; Schonewille, J.T.; Thamrongyoswittayakul, C.; Aiumlamai, S.; Wachirapakom, C.; Everts, H.; Hendriks, W.H.

2012-01-01

An experiment was conducted to test the hypothesis that the supplementation of crude protein (CP) results in rumen acidosis and increased histamine concentrations in dairy cows. Six ruminally fistulated, non-pregnant dry cows were fed three experimental rations in a replicated 3 × 3 Latin square

Pregnancy outcome of “delayed start” GnRH antagonist protocol versus GnRH antagonist protocol in poor responders: A clinical trial study

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Abbas Aflatoonian

2017-08-01

Full Text Available Background: Management of poor-responding patients is still major challenge in assisted reproductive techniques (ART. Delayed-start GnRH antagonist protocol is recommended to these patients, but little is known in this regards. Objective: The goal of this study was assessment of delayed-start GnRH antagonist protocol in poor responders, and in vitro fertilization (IVF outcomes. Materials and Methods: This randomized clinical trial included sixty infertile women with Bologna criteria for ovarian poor responders who were candidate for IVF. In case group (n=30, delayed-start GnRH antagonist protocol administered estrogen priming followed by early follicular-phase GnRH antagonist treatment for 7 days before ovarian stimulation with gonadotropin. Control group (n=30 treated with estrogen priming antagonist protocol. Finally, endometrial thickness, the rates of oocytes maturation, , embryo formation, and pregnancy were compared between two groups. Results: Rates of implantation, chemical, clinical, and ongoing pregnancy in delayed-start cycles were higher although was not statistically significant. Endometrial thickness was significantly higher in case group. There were no statistically significant differences in the rates of oocyte maturation, embryo formation, and IVF outcomes between two groups. Conclusion: There is no significant difference between delayed-start GnRH antagonist protocol versus GnRH antagonist protocol.

Topical non-peptide antagonists of sensory neurotransmitters substance P and CGRP do not modify patch test and prick test reactions

DEFF Research Database (Denmark)

Wallengren, Joanna; Edvinsson, Lars

2014-01-01

developed. Their effect on the skin barrier was measured in terms of transepidermal water loss (TEWL) while permeation was calculated using permeation coefficients. Patch tests in patients allergic to nickel and prick test reactions to histamine were used as models. None of the treatments increased TEWL......, suggesting there to be no impairment of the skin barrier. Permeation coefficients indicated moderate permeation. Histamine prick tests induced a flare with a mean area of 662 + 275 mm(2) and a weal with a mean volume of 49 + 11 mm(3). These reactions as well as histamine-induced pruritus were not affected...... significantly by any of the treatments. Treatment with aprepitant and its vehicle alone resulted in a potentiating of the infiltration of nickel reactions compared with test reactions obtained after no treatment (1147 + 423 mm(3) and 1427 + 566 mm(3) vs 683 +202 mm(3)) (p = 0.03). Telcagepant induced...

Nitric Oxide and Histamine Signal Attempts to Swallow: A Component of Learning that Food Is Inedible in "Aplysia"

Science.gov (United States)

Katzoff, Ayelet; Miller, Nimrod; Susswein, Abraham J.

2010-01-01

Memory that food is inedible in "Aplysia" arises from training requiring three contingent events. Nitric oxide (NO) and histamine are released by a neuron responding to one of these events, attempts to swallow food. Since NO release during training is necessary for subsequent memory and NO substitutes for attempts to swallow, it was suggested that…

Serotonin and Histamine Therapy Increases Tetanic Forces of Myoblasts, Reduces Muscle Injury, and Improves Grip Strength Performance of Dmdmdx Mice

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