WorldWideScience

Sample records for accumulation histamine release

  1. Upregulated expression of substance P in basophils of the patients with chronic spontaneous urticaria: induction of histamine release and basophil accumulation by substance P.

    Science.gov (United States)

    Zheng, Wenjiao; Wang, Junling; Zhu, Wei; Xu, Chiyan; He, Shaoheng

    2016-06-01

    Human basophils have been implicated in the pathogenesis of chronic spontaneous urticaria (CSU), and substance P (SP) is a possible candidate as histamine-releasing factor in some patients with CSU. However, little is known of relationship between basophils and SP in CSU. In the present study, we investigated expression of SP and NK1R on basophils from patients with CSU, and influence of SP on basophil functions by using flow cytometry analysis, basophil challenge, and mouse sensitization model techniques. The results showed that plasma SP level and basophil numbers in CSU patients were higher than that in HC subject. The percentages of SP+ and NK1R+ basophils were markedly elevated in CSU blood in comparison with HC blood. Once added, SP induced up to 41.2 % net histamine release from basophils of CSU patients, which was comparable with that provoked by anti-IgE, and fMLP. It appeared that SP induced dramatic increase in blood basophil numbers of mice following peritoneal injection. Ovalbumin (OVA)-sensitized mice had much more SP+ and NK1R+ basophils in blood than non-sensitized mice. In conclusion, the elevated plasma concentration of SP, upregulated expression of SP and NK1R on basophils, and the ability of SP in induction of basophil degranulation and accumulation indicate strongly that SP is most likely a potent proinflammatory mediator, which contributes greatly to the pathogenesis of CSU through basophils. Inhibitors of SP and blockers of NK1R are likely useful agents for treatment of CSU.

  2. 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...

  3. Modafinil increases histamine release in the anterior hypothalamus of rats.

    Science.gov (United States)

    Ishizuka, Tomoko; Sakamoto, Yasuhiko; Sakurai, Toshimi; Yamatodani, Atsushi

    2003-03-20

    Modafinil, (RS)-2-(Diphenylmethylsulfinyl)acetamide, is a well known wake promoting drug used for the treatment of narcolepsy. We investigated the effect of modafinil on the hypothalamic histamine release in the anesthetized rat using in vivo microdialysis. Modafinil (150 mg/kg, i.p.) increased histamine release by 150% of the basal release. The intracerebroventricular (i.c.v.) injection of modafinil (1 nmol) also increased histamine release, however, when modafinil (1 nmol) was injected directly into the tuberomammillary nucleus, a limited region where cell bodies of the histaminergic neurons are located, histamine release was not altered. These observations suggest that modafinil may promote waking via the activation of the histaminergic system, although it does not appear to be a direct pharmacological target of modafinil.

  4. A method for production and determination of histamine releasing activity from human peripheral blood mononuclear cells

    DEFF Research Database (Denmark)

    Kampen, G T; Poulsen, L K; Reimert, C M

    1997-01-01

    Histamine releasing factors, i.e. cytokines capable of inducing histamine release from basophils or mast cells, have been suggested to be involved in the pathogenesis of, for example, allergic late-phase reactions. Here we describe a controlled method for production and determination of histamine......). The preparations of HRA induced dose- and Ca2+-dependent histamine release from leukocytes. Supernatants of parallel cultures of unstimulated MNC did not induce histamine release. The HRA was neither due to exogenous histamine releasing compounds (e.g. Con A) nor to residual histamine in the preparations of HRA....... The kinetics of HRA induced histamine release (half-maximal release after > 40 min) were slower and more protracted than those of anti-IgE induced histamine release. However, based on a comparison between HRA induced histamine release from leukocytes and purified (97%) basophils, this did not appear to be due...

  5. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Histamine releases PGI2 from human pulmonary artery.

    Science.gov (United States)

    Schellenberg, R R; Duff, M J; Foster, A; Paddon, H B

    1986-08-01

    Histamine caused a triphasic response of human pulmonary artery strips in vitro, consisting of a small initial contraction followed by pronounced relaxation preceding a second contractile response. These characteristics were not seen with other contractile stimuli including 5-hydroxytryptamine, leukotriene D4, and KCl. The relaxant component of this response was ablated by removal of endothelium from the vascular strips or by pretreatment of the tissue with 1 microM indomethacin. Measurement of the PGI2 degradation product 6-keto-PGF1 alpha in supernatants from histamine-challenged tissues confirmed the synthesis of PGI2. Supernatants from unstimulated or leukotriene-challenged tissues contained no detectable amounts of 6-keto-PGF1 alpha. The histamine H1 antagonist diphenydramine inhibited both the contractile and relaxant responses to histamine whereas the H2 antagonist cimetidine affected neither component. The released PGI2 significantly altered the dose-response curve to histamine without inhibiting the maximal contractile responses. We conclude that histamine induces PGI2 formation from pulmonary arterial endothelium via an H1 receptor.

  8. Inhibition of tryptase release from human colon mast cells by histamine receptor antagonists.

    Science.gov (United States)

    He, Shao-Heng; Xie, Hua; Fu, Yi-Ling

    2005-03-01

    The main objective of this study was to investigate the ability of histamine receptor antagonists to modulate tryptase release from human colon mast cells induced by histamine. Enzymatically dispersed cells from human colon were challenged with histamine in the absence or presence of the histamine receptor antagonists, and the tryptase release was determined. It was found that histamine induced tryptase release from colon mast cells was inhibited by up to approximately 61.5% and 24% by the H1 histamine receptor antagonist terfenadine and the H2 histamine receptor antagonist cimetidine, respectively, when histamine and its antagonists were added to cells at the same time. The H3 histamine receptor antagonist clobenpropit had no effect on histamine induced tryptase release from colon mast cells at all concentrations tested. Preincubation of terfenadine, cimetidine or clobenpropit with cells for 20 minutes before challenging with histamine did not enhance the ability of these antihistamines to inhibit histamine induced tryptase release. Apart from terfenadine at 100 microg/ml, the antagonists themselves did not stimulate tryptase release from colon mast cells following both 15 minutes and 35 minutes incubation periods. It was concluded that H1 and H2 histamine receptor antagonists were able to inhibit histamine induced tryptase release from colon mast cells. This not only added some new data to our hypothesis of self-amplification mechanisms of mast cell degranulation, but also suggested that combining these two types of antihistamine drugs could be useful for the treatment of inflammatory bowel disease (IBD).

  9. Histamine release and endothelial leakage from an intravascular contrast medium

    Energy Technology Data Exchange (ETDEWEB)

    Raininko, R.

    1981-04-01

    The endothelial injury produced by meglumine iodamide was studied in the rat aorta. A mixture of blood and contrast medium was more toxic to the endothelium than the pure contrast agent. This difference disappeared after premedication with antihistamine, which did not affect the injury produced by the pure contrast agent. Meglumine iodamide appears to cause a release of histamine from blood but not from the aortic endothelium nor from surrounding tissues in amounts demonstrable by this method. Leucocytes are a source of histamine after intravascular contrast medium administration.

  10. 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...

  11. 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

    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...

  12. 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.)

  13. 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

    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...... 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...... sialic acid in basophil leukocytes is involved in the regulation of histamine release, possibly by a modulation of the transmembraneous calcium fluxes preceding histamine release....

  14. 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...... the acute phase of a standardized thermal injury in healthy volunteers. METHODS: Histamine concentrations in human skin were measured by skin microdialysis technique. Microdialysis fibers were inserted into the dermis in the lower leg in male healthy volunteers. A standardized superficial thermal injury...... was elicited by a heating thermode (49 degrees C) applied to the skin for 5 min. Histamine in dialysate was analyzed for up to 2 h after the injury using two different analytical methods. RESULTS: Spectrofluorometric assay of histamine showed no histamine release in separate studies using 2-min samples over 20...

  15. 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

    We previously observed that human, recombinant interleukin-2 in a pharmacologic dose (200 u/ml) induced histamine release from monocyte-depleted peripheral blood mononuclear cells in vitro. Therefore, we studied the role of various pharmacologic doses of rIL-2 on in vitro histamine release......, for 1, 24 and 48 hours under standard conditions. Histamine was analysed in supernatants using the glass fiber method. Simultaneously, total cell-bound histamine was analysed in lysate from 5 x 10(6) mononuclear cells from all patients and volunteers, thus allowing determination of percent histamine...... release. Supernatant histamine concentration from unstimulated cells was 17.2 +/- 1.5 ng/ml in patients compared to 7.9 +/- 1.0 ng/ml in volunteers (#p Histamine concentration increased...

  16. Modulation of neurotransmitter release via histamine H3 heteroreceptors.

    Science.gov (United States)

    Schlicker, E; Malinowska, B; Kathmann, M; Göthert, M

    1994-01-01

    Presynaptic H3 receptors occur on histaminergic neurones of the CNS (autoreceptors) and on non-histaminergic neurones of the central and autonomic nervous system (heteroreceptors). H3 heteroreceptors, most probably located on the postganglionic sympathetic nerve fibres innervating the resistance vessels and the heart, have been identified in the model of the pithed rat. Furthermore, we could show in superfusion experiments that H3 heteroreceptors also occur on the sympathetic neurones supplying the human saphenous vein and the vasculature of the pig retina and on the serotoninergic, dopaminergic and noradrenergic neurones in the brain of various mammalian species, including man. The effects of three recently described H3 receptor ligands were studied in superfused mouse brain cortex slices. The potency of the novel H3 receptor agonist imetit exceeded that of R-(-)-alpha-methylhistamine (the reference H3 receptor agonist) by one log unit and that of histamine by almost two log units. Clobenpropit was shown to be a competitive H3 receptor antagonist, exhibiting a pA2 as high as 9.6 (exceeding the pA2 of the reference H3 receptor antagonist thioperamide by one log unit). The irreversible antagonism of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) was also studied. Interactions of the H3 heteroreceptor with the dopamine autoreceptor in mouse striatal slices and the alpha 2-autoreceptor in mouse brain cortex slices could be demonstrated. Activation of alpha 2-autoreceptors decreases the H3 receptor-mediated effect. Blockade of alpha 2-autoreceptors increases the H3 receptor-mediated effect only if the alpha 2-autoreceptors are simultaneously activated by endogenous noradrenaline. The H3 receptor-mediated inhibition of noradrenaline release in mouse brain cortex slices was attenuated by the K+ channel blocker tetraethylammonium but this attenuation was abolished by reduction of the Ca2+ concentration in the medium (to compensate for the facilitatory effect of

  17. 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)....

  18. Histamine H3 receptor-mediated inhibition of serotonin release in the rat brain cortex.

    Science.gov (United States)

    Schlicker, E; Betz, R; Göthert, M

    1988-05-01

    Rat brain cortex slices preincubated with 3H-serotonin were superfused with physiological salt solution (containing citalopram, an inhibitor of serotonin uptake) and the effect of histamine on the electrically (3 Hz) evoked 3H overflow was studied. Histamine decreased the evoked overflow in a concentration-dependent manner. The inhibitory effect of histamine was antagonized by impromidine and burimamide, but was not affected by pheniramine, ranitidine, metitepine and phentolamine. Given alone, impromidine facilitated the evoked overflow, whereas burimamide, pheniramine and ranitidine had no effect. The results suggest that histamine inhibits serotonin release in the rat brain cortex via histamine H3 receptors, which may be located presynaptically.

  19. Role of protein kinase C in histamine release from human basophils.

    Science.gov (United States)

    Morita, Y; Takaishi, T; Honda, Z; Miyamoto, T

    1988-02-01

    In this study, we investigated the role of calcium and phospholipid-dependent protein kinase (protein kinase C, PKC) in the modulation of histamine release from human basophils. A novel and potent inhibitor of PKC, K-252a, inhibited the release of histamine induced by anti-IgE in a dose-dependent manner with ID50 (the dose required for 50% inhibition of histamine release) of 2.2 x 10(-8) M. Histamine release stimulated with 12-0-tetradecanoyl-phorbol-13-acetate(TPA) was also suppressed by K-252a with maximal inhibition of 48.0 +/- 9.3% at 10(-7) M. In contrast, K-252a did not inhibit the release of histamine in response to FMLP and ionophore A23187. Another inhibitor of PKC, H-7, exhibited a dose-dependent inhibition of anti-IgE-induced histamine release with ID50 of 8.6 x 10(-4) M. H-8 and HA1004, which closely resemble H-7 in chemical structure but are less potent in inhibiting PKC, did not inhibit histamine release stimulated with anti-IgE, but rather enhanced the release at higher concentrations. These results strongly suggest that PKC activation plays a crucial role in the mediation of IgE-mediated histamine release from human basophils.

  20. 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.

  1. [Histamine releasing activity of dental materials as the indicator of their biocompatibility].

    Science.gov (United States)

    Babakhin, A A; Volozhin, A I; Dubova, L V; Lebedenko, I Iu; Babakhina, Iu A; Zhuravleva, A A; Diubuske, L M

    2008-01-01

    Different types of dental materials (DM) were studied for their capacity to release histamine in vitro from basophils of whole blood of allergic patients and healthy donors using automated and computerized glass fiber-based leukocyte histamine release test (LHRT). It was shown that some types of DM possessed ability to release histamine from basophils and some didn't. There were no differences in histamine releaseability from basophils obtained from allergic patients and healthy donors. LHRT gives opportunity to recognize of DM possessing high or low histamine releaseability as well as to detect individual sensitivity to different DM. Thus, LHRT can be used for preliminary assessment of DM for their biocompatibility and also for individual selection of suitable DM for particular patient to avoid unwanted side effects.

  2. 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...... into lung tissue and perfused with Krebs Ringer buffer at a rate of 3 microl/min. After a 15 min period of steady-state perfusion, anti-IgE and vehicle were injected into the lung tissue above individual fibers. Samples from each fibre were collected for 20 min at 2 min intervals. Histamine was assayed...... fluorometrically. RESULTS: Anti-IgE concentrations of 40-40,000 U/ml dose-dependently released histamine, significant histamine release being demonstrated with anti-IgE concentrations of 400 U/ml and greater. The kinetics of histamine release showed peak values 2-8 min after the injection. Great individual...

  3. Histamine H3 receptor-mediated inhibition of noradrenaline release in the human brain.

    Science.gov (United States)

    Schlicker, E; Werthwein, S; Zentner, J

    1999-01-01

    Stimulation-evoked 3H-noradrenaline release in human cerebrocortical slices was inhibited by histamine (in a manner sensitive to clobenpropit) and by imetit, suggesting H3 receptor-mediated inhibition of noradrenaline release in human brain.

  4. Time-dependent histamine release from stored human blood products

    DEFF Research Database (Denmark)

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

    1996-01-01

    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...... 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...... content at donation, and histamine concentration in samples drawn from the units on days 0, 2, 5, 9, 14, 21, 28 and 35 were analysed with an enzyme-linked immunosorbent assay. Median plasma histamine concentration was 4.8 (range 1.9-14.3) nmol/l (n = 18). Median total cell-bound histamine content was 417...

  5. Inhibition of histamine release from human mast cells by natural chymase inhibitors

    Institute of Scientific and Technical Information of China (English)

    Shao-heng HE; Hua XIE; Xiao-jun ZHANG; Xian-jie WANG

    2004-01-01

    AIM: To investigate the ability of natural chymase inhibitors to modulate histamine release from human mast cells.METHODS: Enzymatically dispersed cells from human lung, tonsil, and skin were challenged with anti-IgE or calcium ionophore A23187 in the absence or presence of the natural chymase inhibitors secretory leukocyte protease inhibitor (SLPI) and α1-antitrypsin, then histamine release was determined. RESULTS: IgE-dependent histamine release from lung, tonsil, and skin mast cells were inhibited by up to 70 %, 61%, and 62%, respectively following incubation with α1-antitrypsin (5000 nmol/L). SLPI 5000 nmol/L was also able to inhibit anti-IgEdependent histamine released from lung, tonsil and skin mast cells by up to approximately 72%, 67%, and 58%,respectively. While neither α1-antitrypsin nor SLPI by themselves altered histamine release from lung, tonsil and skin mast cells, they were able to inhibit calcium ionophore-induced histamine release from lung and tonsil mast cells. CONCLUSION: Both α1-antitrypsin and SLPI could potently inhibit IgE-dependent and calcium ionophoreinduced histamine release from dispersed human lung, tonsil, and skin mast cells in a concentration-dependent manner, which suggested that they were likely to play a protective role in mast cell associated diseases including allergy.

  6. 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

    Histamine release induced by Staphylococcus aureus was examined in cells obtained by bronchoalveolar lavage (BAL) in non-atopic individuals. Approximately half of the individuals responded with mediator release to the bacterium, and the release was found to be time- and concentration dependent....... No difference was found between the patients who responded and those who did not respond in regard to age, sex, smoker/non-smoker, % recovery of BAL-fluid, total cell count, differential cell counts, histamine content per mast cell, or diagnoses. Also stimulation of the BAL-cells with the calcium-ionophore A......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...

  7. Histamine release induced from rat mast cells by the ionophore A23187 in the absence of extracellular calcium

    DEFF Research Database (Denmark)

    Johansen, Torben

    1980-01-01

    Isolated rat mast cells were used to study whether ionophore A23187 could induce histamine release by mobilizing cellular calcium. The histamine release was a slow process which was completed after about 20 min incubation with A23187. The A23187-induced histamine release was inhibited after...... incubation of the cells with EDTA for 1 h in a 37 degrees C water bath in calcium-free medium. Reintroduction of calcium in excess of EDTA induced the release of histamine. The observations suggest that A23187 can induce histamine release by mobilizing a cellular pool of calcium....

  8. 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....

  9. The contribution of histamine release to bronchoconstriction provoked by inhaled benzalkonium chloride in asthma.

    Science.gov (United States)

    Miszkiel, K A; Beasley, R; Rafferty, P; Holgate, S T

    1988-01-01

    1. To investigate the possibility that benzalkonium chloride-induced bronchoconstriction results from the endogenous release of histamine, we examined the effect of the selective histamine antagonists terfenadine and astemizole, on the airways response to inhaled benzalkonium chloride and histamine in 12 asthmatic subjects. 2. Double-blind concentration- and time-course studies were undertaken, 3 h after treatment with terfenadine or matched placebo. 3. Benzalkonium chloride and histamine caused concentration-related falls in FEV1 in all subjects with benzalkonium chloride being 7.4 times less potent as a bronchoconstrictor agonist than histamine. Terfenadine displaced to the right the benzalkonium chloride and histamine concentration-response curves by 3.7 and 111 fold respectively. Terfenadine attenuated the initial (5 min) bronchoconstrictor response to benzalkonium chloride by 40%. However, over the whole 45 min period, the response was reduced by only 13% compared with 86% inhibition of the response to histamine. 4. In an open study, eight of the 12 subjects undertook a time course study with inhaled benzalkonium chloride after pretreatment with the chemically unrelated histamine antagonist astemizole. Astemizole inhibited benzalkonium chloride-induced bronchoconstriction to an almost identical degree as that achieved with terfenadine. 5. We conclude that the initial bronchoconstrictor effect of benzalkonium chloride is due, in part, to histamine release. However, the majority of the adverse effect relates to other, as yet unrecognised effects of this bacteriocidal substance. PMID:2451929

  10. Signaling transduction pathways involved in basophil adhesion and histamine release

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Background 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 β1 andβ2 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). Methods Basophils (purity of 10%-50%) were preincubated with anti-CD29 or anti-CD18 blocking antibodies before used for adhesion study. Basophils were preincubated with the pharmacological inhibitors wortmannin, PP1, PD98059 before used for adhesion and HR study. Cell adherence to bovine serum albumin (BSA) or fibronectin (Fn) was monitored using cell associated histamine as a basophil marker and the histamine was measured by the glass fiber assay.Results Basophil spontaneous adhesion to Fn was inhibited by anti-CD29. Interleukin (IL)-3, granulocyte/macrophage colony stimulating factor (GM-CSF) induced adhesion to BSA was inhibited by anti-CD18. Wortmannin at 1 μmol/L and PP1 at 20 μmol/L strongly interfered with, whereas PD98059 at 50 μmol/L weakly inhibited basophil spontaneous adhesion to Fn. One μmol/L wortmannin strongly inhibited IL-3, IL-5, GM-CSF and anti-IgE induced adhesion to BSA. PP1 at 20 μmol/L partly inhibited anti-IgE induced adhesion. Fifty μmol/L PD98059 marginally inhibited IL-5, weakly inhibited anti-IgE, partly inhibited GM-CSF induced adhesion. Wortmannin, PP1 and PD98059 inhibited anti-IgE (1:100 or 1:1000) induced basophil HR in a dose dependent manner. They inhibited calcium ionophore A23187 (10 μmol/L, 5 μmol/L) induced basophil HR in a dose dependent manner, but to different extend with PP1 being the most efficient.Conclusions Basophil spontaneous adhesion to Fn is mediated by β1-integrins whereas cytokine induced adhesion

  11. Membrane sialic acid influences basophil histamine release by interfering with calcium dependence

    DEFF Research Database (Denmark)

    Jensen, C; Norn, S; Skov, P S

    1987-01-01

    The influence of the cell membrane content of sialic acid on basophil histamine release was examined in vitro in allergic patients and normal controls. Enzymatical removal of sialic acid enhanced histamine release induced by allergen and anti-IgE, whereas an increase in membrane sialic acid content....... This difference, together with the previous finding that alterations in membrane sialic acid content is reflected in the cell sensitivity to extracellular calcium, suggest an interaction between membrane sialic acid and the calcium channels involved in basophil histamine release....

  12. 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...... 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...... be produced as the release of histamine takes place....

  13. Influence of nimodipine, verapamil and lanthanum on histamine release from human basophils

    DEFF Research Database (Denmark)

    Jensen, C B; Thastrup, Ole; Norn, S;

    1987-01-01

    Our previous studies suggest that the membrane content of sialic acid influences histamine release from human basophils by interfering with the transmembraneous calcium fluxes preceding histamine release. In this study we investigated a possible interaction between membrane sialic acid...... and the calcium channels, using the calcium antagonists nimodipine, verapamil and lanthanum. Anti-IgE-induced histamine release was inhibited by verapamil, nimodipine and lanthanum. When cells were pretreated with sialidase in order to remove sialic acid from the cell membrane, the inhibitory action of nimodipine...

  14. Orexin A promotes histamine, but not norepinephrine or serotonin, release in frontal cortex of mice

    Institute of Scientific and Technical Information of China (English)

    Zong-yuan HONG; Zhi-li HUANG; Wei-min QU; Naomi EGUCHI

    2005-01-01

    Aim: To investigate the effects of orexin A on release of histamine, norepinephrine, and serotonin in the frontal cortex of mice. Methods: Samples for measuring histamine, norepinephrine, and serotonin contents were collected by in vivo microdialysis of the frontal cortex of anesthetized mice. The histamine,noradrenaline, and serotonin content in dialysates were measured by HPLC techniques. Results: Intracrebroventricular injection of orexin A at doses of 12.5, 50, and 200 pmol per mouse promoted histamine release from the frontal cortex in a dose-dependent manner. At the highest dose given, 200 pmol, orexin A significantly induced histamine release, with the maximal magnitude being 230% over the mean basal release. The enhanced histamine release was sustained for 140 min, and then gradually returned to the basal level. However, no change in nore pinephrine or serotonin release was observed under application of the same dose of orexin A. Conclusion: These results suggest that the arousal effect of orexin A is mainly mediated by histamine, not by norepinephrine or serotonin.

  15. 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

    We previously observed that human, recombinant interleukin-2 in a pharmacologic dose (200 u/ml) induced histamine release from monocyte-depleted peripheral blood mononuclear cells in vitro. Therefore, we studied the role of various pharmacologic doses of rIL-2 on in vitro histamine release....... Peripheral blood mononuclear cells (5 x 10(6) cells/ml), which also contain basophils, from 13 patients scheduled for elective colorectal cancer surgery and 10 age and sex matched healthy volunteers were stimulated with rIL-2 in concentrations of 0, 50, 100, 200, 450, 900, 1,800 and 3,600 u/ml, respectively......, for 1, 24 and 48 hours under standard conditions. Histamine was analysed in supernatants using the glass fiber method. Simultaneously, total cell-bound histamine was analysed in lysate from 5 x 10(6) mononuclear cells from all patients and volunteers, thus allowing determination of percent histamine...

  16. 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

    was found to release histamine from cells from 7 of the 13 individuals and influenza A virus in 3 of 5 persons. Furthermore, Staph, aureus stimulated the BAL-cells to release leukotriene B4 in 7 of 11 subjects, whereas no release was found by influenza A virus in 7 examined persons. When cells from 4...... 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...

  17. Experimental Researches on Inhibitory Effect of Huoxiang Zhengqi Liquid(藿香正气水) on Histamine Release

    Institute of Scientific and Technical Information of China (English)

    余传星; 朱玲

    2003-01-01

    Objective: To observe the blocking effect of Huoxiang Zhengqi liquid (藿香正气水,HXZQL) on histamine release of basophils. Methods: The study was conducted using HXZQL to neutralize and block IgE and antagonize the effect of IL-3 induced enhancing histamine release of bosaphils. Concentration and percentage of histamine release of bosaphils were tested by the basophil histamine release test. Results: The HXZQL drug-serum had obvious inhibitive effect on degranulation of bosaphils induced by IgE antigen-antibody complex (P<0.05) and can successfully weaken the histamine release of basophils stimulated by IL-3. When compared with those in the untreated group, it showed P<0.01. Conclusion: HXZQL drug-serum may neutralize and block IgE and has inhibitive effects on degranulation of cells when resensitized by antigens. It can also block allergic response type Ⅰ by antagonizing the effect of IL-3 induced enhancing histamine release.

  18. Modulation of histamine release from human colon mast cells by protease inhibitors

    Institute of Scientific and Technical Information of China (English)

    Shao-Heng He; Hua Xie

    2004-01-01

    AIM: To investigate the ability of protease inhibitors to modulate histamine release from human colon mast cells.METHODS: Enzymatically dispersed cells from human colon were challenged with anti-IgE or calcium ionophore A23187 in the absence or presence of tryptase and chymase inhibitors, and histamine release was determined.RESULTS: IgE dependent histamine release from colon mast cells was inhibited by up to approximately 37%, 26% and 36.8% by chymase inhibitors Z-Ile-Glu-Pro-Phe-CO2Me (ZIGPFM), N-Tosyl-L-phenylalanyl-chloromethyl ketone (TPCK), and α1-antitrypsin, respectively. Similarly, inhibitors of tryptase leupeptin, N-tosyl-L-lysine chloromethyl ketone (TLCK), lactoferrin and protamine were also able to inhibit anti-IgE induced histamine release by a maximum of some 48%, 37%, 40% and 34%, respectively. Preincubation of these inhibitors with cells for 20 min before challenged with anti-IgE had small effect on the inhibitory actions of these inhibitors on colon mast cells. A specific inhibitor of aminopeptidase amastatin had no effect on anti-IgE induced histamine release. The significant inhibition of calcium ionophore induced histamine release was also observed with the inhibitors of tryptase and chymase examined. Apart from leupeptin and protamine, the inhibitors tested by themselves did not stimulate colon mast cells.CONCLUSION: It was demonstrated that both tryptase and chymase inhibitors could inhibit IgE dependent and calcium ionophore induced histamine release from dispersed colon mast cells in a concentration dependent of manner, which suggest that they are likely to be developed as a novel class of anti-inflammatory drugs to treat chronic of colitis in man.

  19. Modulation of histamine release by fatty acids. A new in vitro model investigating adverse drug reactions in various species

    OpenAIRE

    Ennis, M.; Lorenz, Wilfried

    1985-01-01

    Histamine release caused by drugs and/or their solvents is a well known phenomenon. In this study, both in vivo (anaesthetized and conscious dogs) and in vitro (isolated rat peritoneal, human and guinea-pig lung mast cells) models were used. Cremophor E1 and six derivatives of 12-hydroxystearic acid were compared for their histamine releasing abilities. Although the three types of isolated mast cells responded similarly, histamine release being observed with DH (the diester of 12-hydroxystear...

  20. 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...... of histamine release from mast cells incubated in glucose-free solution than in complete Tyrode solution (dose-ratio = 20). Like antimycin A (L MICRONMOL/L), PAPAVERINE (3 MICRONMOL/L) CAUSED A DEPLETION OF MAST CELL ATP that was greater in the absence (85%) than in the presence (25%) of extracellular glucose....... 4 These results suggest that dicumarol, like doxantrazole and theophylline, inhibits histamine release without affecting mast cell energy metabolism. In contrast, papaverine probably inhibits release by depleting ATP that is required for exocytosis. 5 Inhibition of histamine release by dibutyryl...

  1. The effect of hardness of food on amygdalar histamine release in rats.

    Science.gov (United States)

    Ishizuka, Tomoko; Sako, Noritaka; Murotani, Tomotaka; Morimoto, Aya; Yamatodani, Atsushi; Ohura, Kiyoshi

    2010-02-01

    When animals eat food, the oral cavity receives a variety of sensory information from food. The hardness of food, which elicits somatic sensation, is thought to affect feeding behavior, however, the details of neuronal mechanism are unclear. The histaminergic system is known to be involved in feeding behavior, and our previous studies indicated that gustatory information activates the histaminergic system, and that palatability of tastants influences its activity. From these findings, we hypothesized that the hardness of food may affect the histaminergic system. Thus, in the present study, we examined the effect of the hardness of food on histamine release in the central nucleus of amygdala when rats consumed either of two types of pellets composed of similar ingredients but having different degrees of hardness: hard and soft pellets. Histamine release was significantly increased in the rat fed with hard pellets. By contrast, histamine release was not enhanced in soft pellets-fed rats. There were no significant differences between the hard and soft pellet intakes during the experimental period. When rats acquired a conditioned aversion to soft pellets, histamine release was increased during feeding, in sharp contrast to no change of histamine release pattern seen during unconditioned soft pellet intake. These observations indicate that the amygdalar histaminergic system is modulated by oral somatic sensation from food, and by palatability of food texture.

  2. A histamine release assay to identify sensitization to Culicoides allergens in horses with skin hypersensitivity.

    Science.gov (United States)

    Wagner, Bettina; Childs, Bronwen A; Erb, Hollis N

    2008-12-15

    Skin hypersensitivity is an allergic disease induced in horses by allergens of Culicoides midges. The condition is typically diagnosed by clinical signs and in some horses in combination with allergy testing such as intradermal skin testing or serological allergen-specific IgE determination. Here, we describe an alternative method for allergy testing: a histamine release assay (HRA) that combines the functional aspects of skin testing with the convenience of submitting a blood sample. The assay is based on the principle that crosslinking of allergen-specific IgE bound via high-affinity IgE receptors to the surfaces of mast cells and basophils induces the release of inflammatory mediators. One of these mediators is histamine. The histamine was then detected by a colorimetric enzyme-linked immunosorbent assay. The histamine assay was used to test 33 horses with skin hypersensitivity and 20 clinically healthy control animals for histamine release from their peripheral blood basophils after stimulation with Culicoides allergen extract or monoclonal anti-IgE antibody. An increased histamine release was observed in the horses with skin hypersensitivity compared to the control group after allergen-specific stimulation with Culicoides extract (p=0.023). In contrast, stimulation with anti-IgE induced similar amounts of released histamine in both groups (p=0.46). For further evaluation of the HRA, we prepared a receiver operating-characteristic (ROC) curve and performed a likelihood-ratio analysis for assay interpretation. Our results suggested that the assay is a valuable diagnostic tool to identify sensitization to Culicoides allergens in horses. Because some of the clinically healthy horses also showed sensitization to Culicoides extract, the assay cannot be used to distinguish allergic from non-allergic animals. The observation that sensitization is sometimes detectable in non-affected animals suggested that clinically healthy horses use immune mechanisms to control the

  3. 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...

  4. Effects of intracerebroventricular injection of histamine and related compounds on corticosterone release in rats.

    Science.gov (United States)

    Tsujimoto, S; Okumura, Y; Kamei, C; Tasaka, K

    1993-07-01

    1. The effects of intracerebroventricular (i.c.v.) injection of histamine and related compounds on plasma adrenocorticotrophic hormone (ACTH) and corticosterone concentrations were studied in conscious rats. 2. Histamine at doses of 5-20 micrograms kg-1 rapidly increased plasma ACTH and corticosterone concentrations almost simultaneously, and subsequent courses were also similar to each other. However, in the case of CRF-41 (i.v.), the plasma ACTH concentration first increased followed by an increase in plasma corticosterone concentration. Even in hypophysectomized rats, a significant increase in plasma corticosterone concentration was induced by histamine at doses of 20 and 50 micrograms kg-1. 3. Histamine at doses of 10 and 20 micrograms kg-1 elicited an increase in the amplitude of adrenal nerve activity, and electrical stimulation to the adrenal nerves resulted in an increase in plasma corticosterone concentration. 4. Both H1-agonist (2-methylhistamine) and H2-agonists (4-methylhistamine and impromidine) also induced similar effects to those of histamine. Pretreatment with pyrilamine caused an inhibition of histamine-induced increase in plasma ACTH and corticosterone concentrations, while both cimetidine and ranitidine failed to inhibit this effect. However, both H2-blockers were effective in inhibiting the 4-methylhistamine-induced elevation of plasma ACTH and corticosterone concentrations. 5. Neither (R)-alpha-methylhistamine nor thioperamide had a significant effect, indicating that the H3-receptor is not involved in the histamine-induced increase in plasma ACTH and corticosterone concentrations. 6. From these findings, it was concluded that (1) electrical signals transmitted from the brain to the adrenal gland through the neurones may be involved in the rapid corticosterone release induced by histamine, and (2) not only H1- but also H2-receptors are implicated in histamine-induced hormone secretions in rats, though the contribution of the H2-receptor is

  5. Inhibition by adenosine of histamine and leukotriene release from human basophils.

    Science.gov (United States)

    Peachell, P T; Lichtenstein, L M; Schleimer, R P

    1989-06-01

    Adenosine inhibited the release of histamine and leukotriene C4 (LTC4) from immunologically-activated basophils in a dose-dependent manner. Structural congeners of adenosine also attenuated the elaboration of these two mediators from stimulated basophils and a rank order of potency for the inhibition was observed following the sequence 2-chloroadenosine greater than or equal to N-ethylcarboxamidoadenosine (NECA) greater than adenosine greater than or equal to R-phenylisopropyladenosine (R-PIA) greater than or equal to S-PIA. These same nucleosides modulated the generation of LTC4 more potently than the release of histamine. A number of methylxanthines, which are antagonists of cell surface adenosine receptors, reversed the inhibition by adenosine and its congeners of the release of both histamine and LTC4 to varying extents. Dipyridamole and nitrobenzylthioinosine (NBTI), agents that block the intracellular uptake of adenosine, antagonized the inhibition of histamine release by adenosine (and 2-chloroadenosine) but failed to reverse the attenuation of LTC4 generation by the nucleoside. These same uptake blockers were unable to antagonize the inhibitory effects of NECA on either histamine or LTC4 release. In purified basophils, NECA and R-PIA, and in that order of decreasing reactivity, increased total cell cyclic adenosine monophosphate (cAMP) levels and inhibited the stimulated release of mediators. In total, these results suggest that the basophil possesses a cell surface adenosine receptor which, on the basis of both pharmacological and biochemical criteria, most closely conforms to an A2/Ra-like receptor. However, in addition to an interaction at the cell surface, studies with agents that block the intracellular uptake of adenosine suggest that the nucleoside may also exert intracellular effects when countering the release of histamine (but not LTC4).

  6. Effects of cannabinoid receptor agonists on immunologically induced histamine release from rat peritoneal mast cells.

    Science.gov (United States)

    Lau, Alaster H Y; Chow, Sharron S M

    2003-03-19

    Immunologic activation of mast cells through the cross-linking of high affinity IgE receptors results in the release of inflammatory mediators which are important in the pathogenesis of allergic reactions. Early studies investigating the effects of palmitoylethanolamide on animal models of inflammation and on rat mast cells led to the hypothesis that endogenous cannabinoids might act as local autacoids which suppressed inflammation by reducing the activation of mast cells. However, more recent studies produced contradicting results. In order to evaluate if cannabinoid receptors are present in mast cells, we studied the effects of endocannabinoids (anandamide and palmitoylethanolamide) and synthetic cannabimimetics (CP 55,940, WIN 55,212-2 and HU-210) on histamine release from rat peritoneal mast cells. When incubated with mast cells alone, only anandamide could induce significant level of histamine release at concentrations higher than 10(-6) M. When mast cells were activated with anti-IgE, the histamine release induced was not affected by anandamide, palmitoylethanolamide and CP 55,940. In contrast, both WIN 55,212-2 and HU-210 enhanced anti-IgE-induced histamine release at 10(-5) M and preincubation did not increase the potency. The histamine releasing action of anandamide and the enhancing effects of WIN 55,212-2 and HU-210 on anti-IgE-induced histamine release were not reduced by the cannabinoid receptor antagonists, AM 281 and AM 630. In conclusion, the present study does not support the hypothesis that cannabinoids suppress mast cell activation. Instead, some of the cannabinoid receptor-directed ligands tested enhanced mast cell activation. However, the high concentrations required and the failure of cannabinoid receptor antagonists to reverse such effects also question the existence of functional cannabinoid receptors in mast cells.

  7. Induction of histamine release in parasitized individuals by somatic and cuticular antigens from Onchocerca volvulus.

    Science.gov (United States)

    González-Muñoz, M; Gárate, T; Puente, S; Subirats, M; Moneo, I

    1999-06-01

    The host immune response in onchocerciasis is believed to contribute to the clinical manifestations of infection. Mazzotti and chronic inflammatory reactions might be mediated by mechanisms involving specific IgE and reactivity of mast cells and basophils to the parasite antigens. In this report, we show that Onchocerca volvulus antigens are capable of inducing histamine release. Three types of extracts were prepared from the parasite: soluble total, surface, and cuticular collagen. Soluble extracts released histamine in all individuals with onchocerciasis at significantly higher levels (P < 0.05) than those found in endemic controls, but similar levels to those found in patients with mansonellosis. However, cuticular collagen induced significantly (P < 0.01) higher histamine release in patients with onchocerciasis than in those with mansonellosis. No reactivity against human type IV collagen was observed. Implications derived from the presence of sensitized basophils in the pathogenesis of onchocerciasis are discussed.

  8. Centrally injected histamine increases posterior hypothalamic acetylcholine release in hemorrhage-hypotensive rats.

    Science.gov (United States)

    Altinbas, Burcin; Yilmaz, Mustafa S; Savci, Vahide; Jochem, Jerzy; Yalcin, Murat

    2015-01-01

    Histamine, acting centrally as a neurotransmitter, evokes a reversal of hemorrhagic hypotension in rats due to the activation of the sympathetic and the renin-angiotensin systems as well as the release of arginine vasopressin and proopiomelanocortin-derived peptides. We demonstrated previously that central nicotinic cholinergic receptors are involved in the pressor effect of histamine. The aim of the present study was to examine influences of centrally administrated histamine on acetylcholine (ACh) release at the posterior hypothalamus-a region characterized by location of histaminergic and cholinergic neurons involved in the regulation of the sympathetic activity in the cardiovascular system-in hemorrhage-hypotensive anesthetized rats. Hemodynamic and microdialysis studies were carried out in Sprague-Dawley rats. Hemorrhagic hypotension was induced by withdrawal of a volume of 1.5 ml blood/100 g body weight over a period of 10 min. Acute hemorrhage led to a severe and long-lasting decrease in mean arterial pressure (MAP), heart rate (HR), and an increase in extracellular posterior hypothalamic ACh and choline (Ch) levels by 56% and 59%, respectively. Intracerebroventricularly (i.c.v.) administered histamine (50, 100, and 200 nmol) dose- and time-dependently increased MAP and HR and caused an additional rise in extracellular posterior hypothalamic ACh and Ch levels at the most by 102%, as compared to the control saline-treated group. Histamine H1 receptor antagonist chlorpheniramine (50 nmol; i.c.v.) completely blocked histamine-evoked hemodynamic and extracellular posterior hypothalamic ACh and Ch changes, whereas H2 and H3/H4 receptor blockers ranitidine (50 nmol; i.c.v.) and thioperamide (50 nmol; i.c.v.) had no effect. In conclusion, centrally administered histamine, acting via H1 receptors, increases ACh release at the posterior hypothalamus and causes a pressor and tachycardic response in hemorrhage-hypotensive anesthetized rats.

  9. Enhancement of mite antigen-induced histamine release by deuterium oxide from leucocytes of chronic urticarial patients

    Energy Technology Data Exchange (ETDEWEB)

    Numata, T.; Yamamoto, S.; Yamura, T.

    1981-09-01

    The mite antigen-induced histamine release from leucocytes of chronic urticarial patients was enhanced in the presence of deuterium oxide, which stabilizes microtubules. This enhancing effect of deuterium oxide on the histamine release from leucocytes may provide a useful means for the detection of allergens in vitro in chronic urticaria.

  10. Kinetic analysis of histamine release due to covalently linked IgE dimers

    Energy Technology Data Exchange (ETDEWEB)

    Dembo, M. (Los Alamos Scientific Lab., NM); Kagey-Sobotka, A.; Lichtenstein, L.M.; Goldstein, B.

    1982-01-01

    We present a kinetic model of histamine release from human basophils due to covalently linked IgE dimers. Comparison of theory with experiment shows that the model gives a good description of histamine release by IgE dimers and allows a number of the parameters of the model to be determined. Comparison with previous models of release by conventional antigens indicates that despite their covalent structure, IgE dimers are subject to the same laws governing inactivation as are antigen produced crosslinks. In addition, the kinetic equation which relates the rate of histamine release to the number of crosslinked Fc/sub e/ receptors per cell is the same for crosslinks formed by IgE dimers as for antigen induced crosslinks. Quantitative fitting of histamine release data also yields a value for the rate constant for crosslink formation by IgE dimer on the cell surface (r/sub x/ approx. = to 5 x 10/sup -10/ cm/sup 2//sec). This rate constant is remarkably high and indicates that the reaction is diffusion controlled.

  11. 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 macroscopi......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...... 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...... secretagogues. Thus, mast cells released 0.4 (0.0-2.0) (median (range)) ng histamine per sample at anti-IgE challenge, and basophils were also anti-IgE responsive. In contrast, mast cells did not respond to FMLP but the corresponding basophils did. Gut mast cells released 0.3 (0.0-1.0) (median (range)) ng...

  12. Histamine-releasing and allergenic properties of opioid analgesic drugs: resolving the two.

    Science.gov (United States)

    Baldo, B A; Pham, N H

    2012-03-01

    Opioid analgesics are amongst the most commonly administered drugs in hospitals. Whether natural or synthetic, they show some common structural features, morphine-like pharmacological action and binding specificity for complementary opioid receptors. Tramadol differs from the other opioid analgesics in possessing monoaminergic activity in addition to its affinity for the µ opioid receptor. Many opioids are potent histamine releasers producing a variety of haemodynamic changes and anaphylactoid reactions, but the relationship of the appearance of these effects to the histamine plasma concentration is complex and there is no direct and invariable relationship between the two. Studies of the histamine-releasing effects, chiefly centred on morphine, reveal variable findings and conclusions often due to a range of factors including differences in technical measurements, dose, mode of administration, site of injection, the anatomical distribution of histamine receptors and heterogeneity of patient responses. Morphine itself has multiple direct effects on the vasculature and other haemodynamically-active mediators released along with histamine contribute to the variable responses to opioid drug administration. Despite their heavy use and occasional apparent anaphylactic-like side-effects, immunoglobulin E antibody-mediated immediate hypersensitivity reactions to the drugs are not often encountered. Uncertainties associated with skin testing with these known histamine-releasers, and the general unavailability of opioid drug-specific immunoglobulin E antibody tests contribute to the frequent failure to adequately investigate and establish underlying mechanisms of reactions by distinguishing anaphylactoid from true anaphylactic reactions. Clinical implications for diagnosis of reactions and some speculations on the rarity of true Type 1 allergies to these drugs are presented.

  13. Topical ophthalmic beta blockers may cause release of histamine through cytotoxic effects of inflammatory cells

    NARCIS (Netherlands)

    Beek, van L.M.; Mulder, M.; Haeringen, van N.J.; Kijlstra, A.

    2000-01-01

    Aim - To evaluate the effects of β blockers used in ophthalmology on the release of histamine from mixed cell preparations containing human leucocytes and basophils. Methods - A mixed leucocyte and basophil preparation was obtained from venous blood of healthy non-atopic volunteers. Cell preparation

  14. 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...

  15. Allergy to formaldehyde: basophil histamine-release test is useful for diagnosis.

    Science.gov (United States)

    Tanaka, Yusuke; Nakase, Yuko; Yamaguchi, Masao; Sugimoto, Naoya; Ohara, Kenshin; Nagase, Hiroyuki; Ohta, Ken

    2014-01-01

    We describe a case of formaldehyde-induced urticaria with a positive test result for serum IgE antibody against this substance. Formaldehyde's slow protein-binding property may explain why basophil histamine-release tests using fresh formaldehyde solutions are not diagnostic, whereas the tests are useful if formaldehyde that had been stored with albumin is used.

  16. Inhibition of Morganella morganii Histidine Decarboxylase Activity and Histamine Accumulation in Mackerel Muscle Derived from Filipendula ulumaria Extracts.

    Science.gov (United States)

    Nitta, Yoko; Yasukata, Fumiko; Kitamoto, Noritoshi; Ito, Mikiko; Sakaue, Motoyoshi; Kikuzaki, Hiroe; Ueno, Hiroshi

    2016-03-01

    Filipendula ulmaria, also known as meadowsweet, is an herb; its extract was examined for the prevention of histamine production, primarily that caused by contaminated fish. The efficacy of meadowsweet was assessed using two parameters: inhibition of Morganella morganii histidine decarboxylase (HDC) and inhibition of histamine accumulation in mackerel. Ellagitannins from F. ulmaria (rugosin D, rugosin A methyl ester, tellimagrandin II, and rugosin A) were previously shown to be potent inhibitors of human HDC; and in the present work, these compounds inhibited M. morganii HDC, with half maximal inhibitory concentration values of 1.5, 4.4, 6.1, and 6.8 μM, respectively. Application of the extracts (at 2 wt%) to mackerel meat yielded significantly decreased histamine accumulation compared with treatment with phosphate-buffered saline as a control. Hence, F. ulmaria exhibits inhibitory activity against bacterial HDC and might be effective for preventing food poisoning caused by histamine.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Effects of inoculation of commercial starter cultures on the quality and histamine accumulation in fermented sausages.

    Science.gov (United States)

    Wang, Xinhui; Ren, Hongyang; Wang, Wei; Zhang, Yin; Bai, Ting; Li, Junxia; Zhu, Wenyou

    2015-02-01

    To meet the requirements of high-quality safe products, starter cultures are used to produce fermented sausages. The effects of 3 commercial starter cultures, namely SM-194, T-SPX, and SM-181, on histamine accumulation and quality parameters including microbial quality, pH, water activity, and total volatile base nitrogen, as well as the color and texture properties, were evaluated during the fermentation and ripening of fermented sausages. Although initial counts of Escherichia coli, Enterobacteriaceae, and Pseudomonas were similar in the 4 batches, the growth of these microorganisms was significantly inhibited (P fermentation and ripening period. The counts of E. coli, Enterobacteriaceae, and Pseudomonas increased to maximum levels of 3.89, 4.41, and 5.15 log10 colony forming units/g in the control sausages, respectively. At the end of ripening, the levels of histamine were 8.85, 0.32, 7.82, and 3.18 mg/kg for batches C, SM-194, T-SPX, and SM-181, respectively. The results revealed that commercial starter cultures, particularly starter cultures SM-194 and SM-181, made a great contribution to histamine reduction. In addition, batches inoculated with starter cultures showed a stronger acidification and lower level of total volatile base nitrogen than the control sample during production (P fermented sausages.

  19. Local histamine release increases leukocyte rolling in the cerebral microcirculation of the mouse.

    Science.gov (United States)

    Yong, T; Zheng, M Q; Linthicum, D S

    1997-10-01

    Histamine-mediated induction of leukocyte rolling and adhesion in the cerebral microcirculation was examined in two inbred strains of mice (SJL/J and BALB/c). A cranial window was surgically prepared for the visualization of the cerebral microcirculation using intra-vital microscopy. Leukocyte rolling and adhesion to pial venular walls were assessed during off-line video playback analyses. The surgical preparation of the cranial windows was found to trigger 'spontaneous' leukocyte rolling, and this was attributed to disruption of dural mast cells and localized release of vasoactive histamine. This spontaneous leukocyte rolling was observed only in the SJL/J strain of mice, and could be prevented by presurgical treatment with the mast cell stabilizer sodium cromoglycate. BALB/c mice did not show 'spontaneous' leukocyte rolling or adhesion; this strain is known to have low numbers of CNS-associated mast cells. Exogenous histamine, applied topically to the cerebral microcirculation via the cranial window in mice pretreated with sodium cromoglycate, produced significant dose-dependent increases in leukocyte rolling and adhesion to pial venules in SJL/J mice, but not in BALB/c mice. Diphenhydramine (H1 receptor antagonist), but not cimetidine (H2 receptor antagonist), abolished both 'spontaneous' and histamine-induced leukocyte rolling. Anti-P-selectin antibody was found efficiently to block both spontaneous and histamine-induced increases in leukocyte rolling, but not leukocyte adhesion.

  20. 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...

  1. Lack of the specific influence of histamine and histamine H1, H2 and H3 receptor ligands on the serotonin uptake and release in rat blood platelets.

    Science.gov (United States)

    Pawlak, D; Malinowska, B; Wollny, T; Godlewski, G; Buczko, W

    1996-01-01

    This work was designed to investigate the influence of histamine, and H1 receptor agonist 2-(2-thiazolyl)ethylamine, H2 receptor agonist dimaprit and H3 receptor agonist R-(-)-alpha-methylhistamine on the serotonin uptake and release in rat blood platelets. Histamine and R-(-)-alpha-methylhistamine (up to 1 mmol/l), 2-(2-thiazolyl)ethylamine (up to 10 mumol/l) and dimaprit (up to 1 mumol/l) failed to affect the serotonin uptake. The concentration-dependent inhibitory effects of higher concentrations of 2-(2-thiazolyl)ethylamine and dimaprit (up to 1 mmol/l) were not diminished by the H1 receptor antagonist dimetindene and the H2 receptor antagonist ranitidine (1 and 100 mumol/l each), respectively. Histamine, 2-(2-thiazolyl)ethylamine, dimaprit and R-(-)-alpha-methylhistamine (up to 10 mumol/l) did not change the serotonin release from rat blood platelets. Our results demonstrate that histamine and histamine H1, H2 and H3 receptor agonists do not affect in a specific manner the serotonin uptake and release in rat blood platelets.

  2. 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

    Endogenous histamine-releasing factors (HRFs) are involved in 30-60% of patients with chronic urticaria (CU). Evidence for their existence comes from in vivo studies of autoreactivity with the autologous serum skin test (ASST), in vitro immunoassays demonstrating autoantibodies against the immuno......Endogenous histamine-releasing factors (HRFs) are involved in 30-60% of patients with chronic urticaria (CU). Evidence for their existence comes from in vivo studies of autoreactivity with the autologous serum skin test (ASST), in vitro immunoassays demonstrating autoantibodies against...... 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...

  3. 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...

  4. Inhibition of noradrenaline release from the sympathetic nerves of the human saphenous vein by presynaptic histamine H3 receptors.

    Science.gov (United States)

    Molderings, G J; Weissenborn, G; Schlicker, E; Likungu, J; Göthert, M

    1992-07-01

    The human saphenous vein was used to examine whether presynaptic histamine receptors can modulate noradrenaline release and, if so, to determine their pharmacological characteristics. Strips of this blood vessel were incubated with [3H]noradrenaline and subsequently superfused with physiological salt solution containing desipramine and corticosterone. Electrically (2 Hz) evoked 3H overflow was inhibited by histamine and the H3 receptor agonist R-(-)-alpha-methylhistamine. Histamine-induced inhibition of electrically evoked tritium overflow was not affected by alpha 2-adrenoceptor blockade by rauwolscine. S-(+)-alpha-methylhistamine (up to 10 mumol/l) as well as the histamine H1 and H2 receptor agonists 2-(2-thiazolyl)ethylamine (up to 3 mumol/l) and dimaprit (up to 30 mumol/l), respectively, were ineffective. The selective histamine H3 receptor antagonist thioperamide abolished the inhibitory effect of histamine. The histamine H2 and H1 receptor antagonists ranitidine and pheniramine, respectively, did not affect the histamine-induced inhibition of evoked tritium overflow. The present results are compatible with the suggestion that the sympathetic nerves of the human saphenous vein are endowed with inhibitory presynaptic histamine receptors of the H3 class.

  5. Effect of subarachnoid hemorrhage on contractile responses and noradrenaline release evoked in cat cerebral arteries by histamine

    Energy Technology Data Exchange (ETDEWEB)

    Lobato, R.D.; Marin, J.; Salaices, M.; Rico, M.L.; Sanchez, C.F.

    1981-10-01

    This study analyzes the changes induced by subarachnoid hemorrhage (SAH) on the contractile responses and the noradrenaline release evoked in cat cerebral arteries by histamine. The dose-dependent vasoconstriction induced by histamine on the cerebral arteries of normal cats was significantly reduced by diphenhydramine and phentolamine. When SAH was produced 3 and 7 days before the experiment, the histamine-induced vasoconstriction also decreased. Thereafter, a tendency to normalization in the contractile vascular responses was observed such that in 15 days after the hemorrhage it was not significantly different from that found in controls animals. The decrease in the contractile responses to histamine provoked by SAH was similar to that seen after pretreatment with intracisternal injections of 6-hydroxydopamine. The amount of radioactivity released by histamine following preincubation with /sup 3/H-noradrenaline from the cerebral arteries of cats exposed to SAH 3, 7, and 15 days before the experiment was significantly reduced when compared with controls. Moreover, the basal level of tritium release and the radioactivity retained at the end of the experiment were also decreased after SAH. Results indicate histamine releases noradrenaline from cat cerebral arteries, and SAH produce a transient denervation of the perivascular adrenergic nerve endings, which explained by the impairment of the indirect adrenergic mechanism involved in the overall contractile response elicited by this amine in cerebral arteries. Histamine does not seem to play a significant role in the production of the cerebral vasospasm occurring after SAH.

  6. Possible participation of histamine H3 receptors in the modulation of noradrenaline release from rat spinal cord slices.

    Science.gov (United States)

    Celuch, S M

    1995-12-12

    Rat spinal cord slices prelabelled with [3H]noradrenaline were superfused with a medium containing 1 mu M desipramine plus 0.3 mu M phentolamine. Histamine (0.01-10 mu M) and the selective histamine H3 receptor agonist R-(-)-alpha-methylhistamine (0.001-10 mu M) caused a concentration-dependent decrease in the release of radioactivity evoked by electrical field stimulation (0.8 Hz, 20 mA, 2 min). The inhibitory effect of histamine was not modified by either pyrilamine (1 mu M) or ranitidine (10 mu M), but it was antagonized by burimamide (1 mu M). The inhibitory action of histamine (1 mu M) was attenuated by pertussis toxin (3 mu g/ml) and was abolished by N-ethylmaleimide (30 mu M). Neither forskolin (10 mu M) nor rolipram (100 mu M), nor the combination of both drugs, modified the inhibitory effect of histamine. Histamine (1 mu M) did not modify the overflow of tritium induced by electrical stimulation in the absence of phentolamine. The present results suggest that in the rat spinal cord the release of noradrenaline elicited by electrical stimulation is negatively modulated by histamine, probably through the activation of histamine H3 receptors. This modulatory mechanism is likely to involve the participation of regulatory Go/Gi proteins.

  7. Effect of allergen-specific immunotherapy on recombinant human interleukin 3-mediated amplification of allergen-induced basophil histamine release.

    Science.gov (United States)

    Kowal, Krzysztof; Nolte, Hendrik; Skov, Per Stahl; DuBuske, Lawrence M

    2005-01-01

    Decreased allergen-induced histamine release from peripheral blood basophils in allergic rhinitis patients treated with specific immunotherapy (SIT) correlates with clinical outcomes of SIT. The aim of this study was to investigate if decreased histamine release is a permanent effect of SIT. Fifty-one patients (mean age, 35.3 years) with allergic rhinitis, diagnosed based on clinical history and positive skin-prick test results to common aeroallergens, were studied. Twenty-three patients had never received SIT (group A), and 28 patients had been treated with inhalant allergen extracts (group B). Eleven patients from group A participated in a prospective part of this study. Basophil histamine release in these patients was evaluated before (TO) and after-1 year (TI) of SIT. Histamine release from peripheral blood with and without interleukin (IL)-3 pretreatment was performed using the glass-fiber-based histamine release test. Brief pretreatment of whole blood basophils with one of the four concentrations (0.01, 0.1, 1, or 10 ng/mL) of recombinant human IL(rhIL)-3, rhIL-5, or rh-granulocyte-macrophage colony-stimulating factor resulted in a significant amplification of allergen-induced basophil histamine release. The amplification using cytokines at the optimal concentrations was the greatest with rhIL-3 and the lowest with rhIL-5; therefore, for further studies rhIL-3 was used. Prospective analysis showed no significant difference in allergen-induced basophil histamine release on rhIL-3 pretreatment after 1 year of SIT (192.7 +/- 75.3 ng and 176.1 +/- 76.4 ng for T0 and T1, respectively; p = 0.18). Short-term SIT does not decrease rhIL-3-mediated amplification of allergen-induced histamine release from peripheral blood basophils.

  8. A Case of Anaphylactic Reaction Following Matsutake Mushroom Ingestion: Demonstration of Histamine Release Reaction of Basophils

    OpenAIRE

    Takako Toda; Masao Yamaguchi; Yuko Nakase; Naoya Sugimoto; Maho Suzukawa; Hiroyuki Nagase; Ken Ohta

    2010-01-01

    Background: Matsutake mushroom is not recognized as a common food allergen. However, several case reports have suggested that this mushroom can induce anaphylaxis on rare occasions. Case Summary: We report a woman with bronchial asthma, who experienced two episodes of Matsutake-induced anaphylaxis. Both the prick-to-prick test and basophil histamine release test showed positive reactions to this mushroom in this patient, but not in control subjects. Discussion: Matsutake mushroom can, o...

  9. Mechanism of histamine release from rat mast cells induced by the ionophore A23187: effects of calcium and temperature

    DEFF Research Database (Denmark)

    Johansen, Torben

    1978-01-01

    1 The mechanism of histamine release from a pure population of rat mast cells induced by the lipid soluble antibiotic, A23187, has been studied and compared with data for anaphylactic histamine release reported in the literature. 2 Histamine release induced by A23187 in the presence of calcium 10......(-3) mol/l was completed in 10 minutes. By preincubation of the mast cells with A23187 for 10 min in the absence of calcium the histamine release induced by calcium, 10(-3) mol/l or 5 x 10(-3) mol/l, was completed in 90 s and 45 s, respectively. 3 A23187-induced histamine release was maximal with calcium...... 10(-3) mol/l when the cells were incubated at 33 to 39 degrees C for 10 minutes. 4 The cellular mechanism, which was stimulated by A23187 and calcium for the release of histamine, was irreversibly inactivated by incubation at 45 degrees C. 5 An inhibition of energy metabolism was excluded...

  10. Colorectal mucosal histamine release by mucosa oxygenation in comparison with other established clinical tests in patients with gastrointestinally mediated allergy

    Institute of Scientific and Technical Information of China (English)

    M Raithel; M Weidenhiller; R Abel; HW Baenkler; EG Hahn

    2006-01-01

    AIM: This study evaluated colorectal mucosal histamine release in response to blinded food challenge-positive and -negative food antigens as a new diagnostic procedure.METHODS: 19 patients suffering from gastrointestinally mediated allergy confirmed by blinded oral provocation were investigated on grounds of their case history, skin prick tests, serum IgE detection and colorectal mucosal histamine release by ex vivo mucosa oxygenation.Intact tissue particles were incubated/stimulated in an oxygenated culture with different food antigens for 30 min. Specimens challenged with anti-human immunoglobulin E and without any stimulus served as positive and negative controls, respectively. Mucosal histamine release (% of total biopsy histamine content) was considered successful (positive), when the rate of histamine release from biopsies in response to antigens reached more than twice that of the spontaneous release. Histamine measurement was performed by radioimmunoassay.RESULTS: The median (range) of spontaneous histamine release from colorectal mucosa was found to be 3.2 (0.1%-25.8%) of the total biopsy histamine content. Food antigens tolerated by oral provocation did not elicit mast cell degranulation 3.4 (0.4%-20.7%, P = 0.4), while anti-IgE and causative food allergens induced a significant histamine release of 5.4 (1.1%-25.6%, P = 0.04) and 8.1 (1.5%-57.9%, P = 0.008), respectively.12 of 19 patients (63.1%) showed positive colorectal mucosal histamine release in accordance with the blinded oral challenge responding to the same antigen (s),while the specificity of the functional histamine release to accurately recognise tolerated foodstuffs was found to be 78.6%. In comparison with the outcome of blinded food challenge tests, sensitivity and specificity of history (30.8% and 57.1%), skin tests (47.4% and 78.6%) or antigen-specific serum IgE determinations (57.9% and 50%) were found to be of lower diagnostic accuracy in gastrointestinally mediated allergy

  11. Histamine H3A receptor-mediated inhibition of noradrenaline release in the mouse brain cortex.

    Science.gov (United States)

    Schlicker, E; Behling, A; Lümmen, G; Göthert, M

    1992-04-01

    Mouse brain cortex slices preincubated with 3H-noradrenaline were superfused with physiological salt solution containing desipramine plus a drug with alpha 2-adrenoceptor antagonist properties, and the effects of histamine receptor ligands on the electrically (0.3 Hz) evoked tritium overflow were studied. The evoked overflow (from slices superfused with phentolamine) was inhibited by histamine (pIC35 6.53), the H3 receptor agonist R-(-)-alpha-methylhistamine (7.47) and its S-(+)-enantiomer (5.82) but not influenced by the H1 receptor agonist 2-(2-thiazolyl)-ethylamine 3.2 mumol/l and the H2 receptor agonist dimaprit 10 mumol/l. The inhibitory effect of histamine was not affected by the H1 receptor antagonist dimetindene 1 mumol/l and the H2 receptor antagonist ranitidine 10 mumol/l. The concentration-response curve of histamine (determined in the presence of rauwolscine) was shifted to the right by the H3 receptor antagonists thioperamide (apparent pA2 8.67), impromidine (7.30) and burimamide (6.82) as well as by dimaprit (6.16). The pA2 values of the four drugs were compared with their affinities for H3A and H3B binding sites in rat brain membranes (West et al. 1990 Mol Pharmacol 38:610); a significant correlation was obtained for the H3A, but not for the H3B sites. The results suggest that noradrenaline release in the mouse brain cortex is inhibited by histamine via H3A receptors and that dimaprit is an H3 receptor antagonist of moderate potency.

  12. Detection of homocytotropic antibody in lambs infested with the louse, Bovicola ovis, using a basophil histamine-release assay.

    Science.gov (United States)

    Pfeffer, A; Phegan, M D; Bany, J

    1997-07-01

    The utility of a basophil histamine-release assay using washed whole blood cells was examined in lambs and was used to determine if homocytotropic antibody with specificity for Bovicola ovis was produced in response to infestation with the louse. Maximal histamine release in the assay in response to Concanavalin A, anti-ovine IgE monoclonal antibody and, in sensitized lambs, to B. ovis antigen ranged from 18 to 48%. Histamine release from blood cells in response to B. ovis antigen was significantly higher in louse-infested lambs than in louse-naive lambs and was significantly correlated with louse and cockle scores. Passive cutaneous anaphylaxis (PCA) tests were negative with sera obtained from the lambs at the same time as blood for the basophil histamine-release assay. Serum histamine levels also were significantly higher in the louse-infested lambs than in louse-naive lambs and were significantly correlated with louse and cockle scores. The present results support a role for B. ovis-specific homocytotropic antibody in the development of cockle and indicate that the basophil histamine-release assay is more sensitive than the PCA test.

  13. Histamine H3 receptor activation inhibits dopamine synthesis but not release or uptake in rat nucleus accumbens.

    Science.gov (United States)

    Aquino-Miranda, Guillermo; Escamilla-Sánchez, Juan; González-Pantoja, Raúl; Bueno-Nava, Antonio; Arias-Montaño, José-Antonio

    2016-07-01

    We studied the effect of activating histamine H3 receptors (H3Rs) on rat nucleus accumbens (rNAcc) dopaminergic transmission by analyzing [(3)H]-dopamine uptake by synaptosomes, and dopamine synthesis and depolarization-evoked [(3)H]-dopamine release in slices. The uptake of [(3)H]-dopamine by rNAcc synaptosomes was not affected by the H3R agonist RAMH (10(-10)-10(-6) M). In rNAcc slices perfusion with RAMH (1 μM) had no significant effect on [(3)H]-dopamine release evoked by depolarization with 30 mM K(+) (91.4 ± 4.5% of controls). The blockade of dopamine D2 autoreceptors with sulpiride (1 μM) enhanced K(+)-evoked [(3)H]-dopamine release (168.8 ± 15.5% of controls), but under this condition RAMH (1 μM) also failed to affect [(3)H]-dopamine release. Dopamine synthesis was evaluated in rNAcc slices incubated with the l-dihydroxyphenylalanine (DOPA) decarboxylase inhibitor NSD-1015 (1 mM). Forskolin-induced DOPA accumulation (220.1 ± 10.4% of controls) was significantly reduced by RAMH (41.1 ± 6.5% and 43.5 ± 9.1% inhibition at 100 nM and 1 μM, respectively), and this effect was prevented by the H3R antagonist ciproxifan (10 μM). DOPA accumulation induced by preventing cAMP degradation with IBMX (iso-butyl-methylxantine, 1 mM) or by activating receptors for the vasoactive intestinal peptide (VIP)/pituitary adenylate cyclase-activating peptide (PACAP) with PACAP-27 (1 μM) was reduced (IBMX) or prevented (PACAP-27) by RAMH (100 nM). In contrast, DOPA accumulation induced by 8-Bromo-cAMP (1 mM) was not affected by RAMH (100 nM). These results indicate that in rNAcc H3Rs do not modulate dopamine uptake or release, but regulate dopamine synthesis by inhibiting cAMP formation and thus PKA activation. This article is part of the Special Issue entitled 'Histamine Receptors'.

  14. Autologous serum skin test reactivity and basophil histamine release test in patients with nasal polyposis: preliminary results.

    Science.gov (United States)

    Zambetti, G; Ciofalo, A; Soldo, P; Fusconi, M; Romeo, R; Greco, A; Altissimi, G; Macri, G F; Marinelli, C; Pagliuca, G; De Vincentiis, M

    2010-01-01

    An eosinophilic inflammatory process is generally observed in patients suffering from nasal polyposis (NP), however its onset has not yet been defined. It has been suggested that immune activation of inflammatory cells may be the cause. The aim of this study is to verify whether autoantibodies and/or histamine-releasing factors are present in the serum of patients suffering from NP. In fact, we assume that autoantibodies and/or histamine-releasing factors, as already demonstrated in chronic idiopathic urticaria and asthma, may be involved in the pathogenesis of NP. In this case-control analytical study 40 patients with NP and 27 control subjects underwent the in vivo autologous serum skin test (ASST). The sera from 6 patients suffering from NP and 9 control group subjects, who had all been previously studied and randomly selected, underwent basophil histamine release assay from normal donor as a pilot study. The ASST showed positive results in 55% of patients suffering from NP versus 8% of the control group (p= .00006), the basophil histamine release test (BHRT) turned out positive in all patients tested and in 11% of the control group. We found a weak positive correlation between the percentage of histamine release and the wheal diameter. ASST reactivity is very frequent in patients suffering from NP, thus suggesting the presence of histamine-releasing factors in the blood stream. The BHRT was positive in the serum of all patients, thus suggesting the presence of anti-FcepsilonRI, anti-IgE autoantibodies and/or other histamine-releasing factors, the presence of which can play a role in triggering and maintaining the eosinophilic inflammatory process in NP.

  15. A positive serum basophil histamine release assay is a marker for ciclosporin-responsiveness in patients with chronic spontaneous urticaria

    DEFF Research Database (Denmark)

    Iqbal, Kamran; Bhargava, Kapil; Skov, Per Stahl;

    2012-01-01

    ABSTRACT: The electronic records of 398 patients with chronic spontaneous urticaria (CSU) who had had a serum basophil histamine release assay (BHRA) performed as a marker of functional autoantibodies were audited. The BHRA was positive in 105 patients (26.4%). Fifty eight were treated with ciclo...... with ciclosporin because they were H1 anti-histamine unresponsive. CSU patients with a positive BHRA were more likely to respond clinically (P...

  16. Histamine, histamine intoxication and intolerance.

    Science.gov (United States)

    Kovacova-Hanuskova, E; Buday, T; Gavliakova, S; Plevkova, J

    2015-01-01

    Excessive accumulation of histamine in the body leads to miscellaneous symptoms mediated by its bond to corresponding receptors (H1-H4). Increased concentration of histamine in blood can occur in healthy individuals after ingestion of foods with high contents of histamine, leading to histamine intoxication. In individuals with histamine intolerance (HIT) ingestion of food with normal contents of histamine causes histamine-mediated symptoms. HIT is a pathological process, in which the enzymatic activity of histamine-degrading enzymes is decreased or inhibited and they are insufficient to inactivate histamine from food and to prevent its passage to blood-stream. Diagnosis of HIT is difficult. Multi-faced, non-specific clinical symptoms provoked by certain kinds of foods, beverages and drugs are often attributed to different diseases, such as allergy and food intolerance, mastocytosis, psychosomatic diseases, anorexia nervosa or adverse drug reactions. Correct diagnosis of HIT followed by therapy based on histamine-free diet and supplementation of diamine oxidase can improve patient's quality of life.

  17. Potentiation of histamine release by Microfungal (1-->3)- and (1-->6)-beta-D-glucans

    DEFF Research Database (Denmark)

    Holck, Peter; Sletmoen, Marit; Stokke, Bjørn Torger

    2007-01-01

    : curdlan [a linear (1-->3)-beta-D-glucan], laminarin and scleroglucan, and furthermore with pustulan, a linear (1-->6)-beta-D-glucan. Histamine release was not observed on exposure to the glucans only, but in the presence of anti-immunoglobulin E (IgE) antibody or specific antigens, all the glucans...... investigated led to an enhancement of the IgE-mediated histamine release. The glucans induced a significant potentiation of the mediator release when present at concentrations in the range of 2-5 x 10(-5) M. These results suggest that (1-->3)-beta-D-glucan as well as (1-->6)-beta-D-glucan aggravates Ig......E-mediated histamine release. Knowledge concerning the effects of glucans on immune responses may be of importance for understanding and treating inflammatory and allergic diseases....

  18. 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 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.

  19. 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...

  20. The response of a human bronchial epithelial cell line to histamine: Intracellular calcium changes and extracellular release of inflammatory mediators

    Energy Technology Data Exchange (ETDEWEB)

    Noah, T.L.; Paradiso, A.M.; Madden, M.C.; McKinnon, K.P.; Devlin, R.B. (Department of Pediatrics, University of North Carolina School of Medicine, Chapel Hill (United States))

    1991-11-01

    Epithelial cells are likely to modulate inflammation and tissue repair in the airways, but the factors responsible for these processes remain unclear. Because human airway epithelia are infrequently available for in vitro studies, transformed epithelial cell lines are of interest as models. The authors therefore investigated the response of an SV-40/adenovirus-transformed human bronchial epithelial cell line (BEAS-2B) to histamine, a mediator with relevance for airway diseases. The intracellular calcium response to histamine (10(-4) M) was measured, using Fura-2 and microspectrofluorimetry. Histamine induced a transient increase in intracellular calcium that originated from intracellular sources; this effect was inhibited by the H1 receptor antagonist diphenhydramine, suggesting that BEAS cells retain functioning histamine receptors. BEAS cells were grown to confluence on microporous, collagen-coated filters, allowing measurement of vectorial release of soluble mediators. Monolayers exposed to histamine for 30 min released interleukin-6 and fibronectin in the apical direction, in a dose-dependent manner. Little eicosanoid production was induced by histamine, either in the apical or the basolateral direction, although BEAS cells constitutively produced small amounts of prostaglandin E2 and 15-HETE. However, these cells formed large amounts of eicosanoids in response to ozone exposure as a positive control. Comparison of their data with published reports for human airway epithelia in primary culture suggests that the BEAS cell line is, in a number of respects, a relevant model for the study of airway epithelial responses to a variety of stimuli.

  1. Evaluation of the correlation and reproducibility between histamine, IL-4, and IL-13 release from human basophils.

    Directory of Open Access Journals (Sweden)

    Nahid Eskandari

    2014-06-01

    Full Text Available Human basophils play a key role in allergic diseases such as asthma and in a variety of immunological disorders. The generation of IL-4 and IL-13 can be induced from basophil by IgE-mediated and non-IgE-mediated mechanisms. Time and stimulus-dependent differences in the regulation of these cytokines could have relevance to their biological effects. The aim of the present study was activation of basophils in order to evaluate the extent of histamine, IL-4, and IL-13 generations. Basophil-enriched suspensions were prepared by Percoll gradients. The release of histamine and cytokines was assessed after activation with either anti-human IgE (1/1000 or 1/10000, 4 h or 24 h or IL-3 (100 ng/ ml, 24 h. Results were analysed statistically, using ANOVA test. Using anti-IgE, there was no significant correlation between the extent of either IL-4 (r=0.24, p=0.35 or IL-13 (r=0.47, p=0.098 and histamine release. Using IL-3 as stimulator, results showed that the extent of IL-13 correlated with histamine release(r=0.44, p=0.036. There was no correlation between the extent of IL-4 and the degree of either histamine (r=0.077, p=0.72 or IL-13 (r=0.162, p=0.5. The reproducibility of cytokines isolated from the same donor (on different occasions indicated that the ability of anti-IgE to induce cytokines was consistently similar for a given donor. Our data showed that the pathways leading to IL-3-triggering histamine release and IL-13 generation show similarity. Donor-dependent differences may be responsible for this wide range in the extent of releasibility. The ability of IL-3 to release cytokines from basophils showed a wider range.

  2. Evaluation of the correlation and reproducibility between histamine, IL-4, and IL-13 release from human basophils.

    Science.gov (United States)

    Eskandari, Nahid; Bastan, Reza; Ahmadi, Maryam; Peachell, Peter T

    2014-06-01

    Human basophils play a key role in allergic diseases such as asthma and in a variety of immunological disorders. The generation of IL-4 and IL-13 can be induced from basophil by IgE-mediated and non-IgE-mediated mechanisms. Time and stimulus-dependent differences in the regulation of these cytokines could have relevance to their biological effects. The aim of the present study was activation of basophils in order to evaluate the extent of histamine, IL-4, and IL-13 generations. Basophil-enriched suspensions were prepared by Percoll gradients. The release of histamine and cytokines was assessed after activation with either anti-human IgE (1/1000 or 1/10000, 4 h or 24 h) or IL-3 (100 ng/ ml, 24 h). Results were analysed statistically, using ANOVA test. Using anti-IgE, there was no significant correlation between the extent of either IL-4 (r=0.24, p=0.35) or IL-13 (r=0.47, p=0.098) and histamine release. Using IL-3 as stimulator, results showed that the extent of IL-13 correlated with histamine release(r=0.44, p=0.036). There was no correlation between the extent of IL-4 and the degree of either histamine (r=0.077, p=0.72) or IL-13 (r=0.162, p=0.5). The reproducibility of cytokines isolated from the same donor (on different occasions) indicated that the ability of anti-IgE to induce cytokines was consistently similar for a given donor. Our data showed that the pathways leading to IL-3-triggering histamine release and IL-13 generation show similarity. Donor-dependent differences may be responsible for this wide range in the extent of releasibility. The ability of IL-3 to release cytokines from basophils showed a wider range.

  3. The effect of orexin-A and -B on the histamine release in the anterior hypothalamus in rats.

    Science.gov (United States)

    Ishizuka, Tomoko; Yamamoto, Yumiko; Yamatodani, Atsushi

    2002-04-26

    The neuropeptides orexin-A and -B have been reported to be appetite-stimulating peptides, but they are also known as important factors that control arousal state. We studied the effects of orexin-A and -B on the hypothalamic histamine release using in vivo microdialysis. A significant and sustained increase in histamine release was observed by intracerebroventricular injection of 1 nmol of orexin-A, but not by the same dose of orexin-B. An increased dose of orexin-B to 5 nmol facilitated histamine release, although this effect was much less potent than orexin-A. These findings suggest that both of the orexins play important roles in the regulation of waking through the activation of histaminergic system.

  4. Effects of methyl p-hydroxybenzoate (methyl paraben) on Ca2+ concentration and histamine release in rat peritoneal mast cells

    OpenAIRE

    Fukugasako, Sanae; Ito, Shinichi; Ikemoto, Yoshimi

    2003-01-01

    Mechanisms of methyl p-hydroxybenzoate (methyl paraben) action in allergic reactions were investigated by measuring the intracellular Ca2+ concentration ([Ca2+]i) and histamine release in rat peritoneal mast cells (RPMCs).In the presence or absence of extracellular Ca2+, methyl paraben (0.1–10 mM) increased [Ca2+]i, in a concentration-dependent manner. Under both the conditions, methyl paraben alone did not evoke histamine release.In RPMCs pretreated with a protein kinase C (PKC) activator (p...

  5. Ethacrynic acid inhibition of histamine release from rat mast cells: effect on cellular ATP levels and thiol groups

    DEFF Research Database (Denmark)

    Johansen, Torben

    1983-01-01

    The experiments concerned the effect of ethacrynic acid (0.5 mM) on the adenosine triphosphate (ATP) content of rat mast cells and the effect on histamine release induced by the ionophore A23187 (10 microM). Ethacrynic acid decreased the ATP level of the cells in presence of antimycin A and glucose...... as well as in presence of 2-deoxyglucose. A23187-induced histamine release was inhibited by ethacrynic acid, and this inhibition was completely reversed by dithiothreitol. These observations may indicate that ethacrynic acid inhibits glycolytic and respiratory energy production in rat mast cells...

  6. Radiation-Released Histamine in the Rhesus Monkey as Modified by Mast Cell Depletion and Antihistamine

    Science.gov (United States)

    1975-06-01

    mast cell histamine depleter, compound 48/80 (1mg/kg per day) for four consecutive days and then irradiated (4000 rads), histamine concentrations did not change significantly. When 48/80 was given 20 min after irradiation, histamine concentrations changed from 18 + or - 2 ng/ml to a maximum of 35 + or - 9 ng/ml after 48/80 injection.

  7. Different role of cAMP dependent protein kinase and CaMKII in H3 receptor regulation of histamine synthesis and release.

    Science.gov (United States)

    Moreno-Delgado, D; Gómez-Ramírez, J; Torrent-Moreno, A; González-Sepúlveda, M; Blanco, I; Ortiz, J

    2009-12-15

    Histamine H(3) autoreceptors induce a negative feedback on histamine synthesis and release. While it is known that cAMP/cAMP dependent protein kinase (PKA) and Ca(2+)/CaMKII transduction pathways mediate H(3) effects on histamine synthesis, the pathways regulating neuronal histamine release are poorly known. Given the potential use of H(3) ligands in cognitive diseases, we have developed a technique for the determination of H(3) effects on histamine synthesis and release in brain cortical miniprisms. Potassium-induced depolarization effects were impaired by blockade of calcium entry through N and P/Q channels, as well as of CaMKII, but release was not affected by activators or inhibitors of the cAMP/PKA pathway (1-methyl-3-isobutylxanthine (IBMX), N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate sodium salt (db-cAMP) or myristoyl PKA inhibitor peptide 14-22 (PKI(14-22)). In contrast, forskolin stimulated histamine release, although independently of PKA. Stimulation of histamine H(3) receptors with the agonist imetit markedly reduced the depolarization increase of histamine release, apparently through P/Q calcium channel inhibition. The H(3) antagonist/inverse agonist thioperamide modestly stimulated histamine release. Thioperamide effect on release was not modified by the PKA inhibitor PKI(14-22), but it was blocked by the CaMKII inhibitor KN-62. These results indicate that H(3) autoreceptors regulate neuronal histamine release (1) independently of the cAMP/PKA cascade, and (2) through modulation of calcium entry and CaMKII activation during depolarization.

  8. Antigen-induced and non-antigen-induced histamine release from rat mast cells sensitized with mouse antiserum.

    Directory of Open Access Journals (Sweden)

    Kurose,Masao

    1981-10-01

    Full Text Available Marked IgE-mediated histamine release from rat mast cells sensitized in vitro with mouse antiserum occurs in the presence of added Ca++ and phosphatidylserine (PS, although a considerable degree of antigen-induced histamine release which may utilize intracellular or cell-bound calcium is also observed. The decay in the responsiveness to Ca++ of the sensitized cells stimulated by antigen in Ca++-free medium in the presence of PS is relatively slow, and maximum release is produced by Ca++ added 1 min after antigen. Histamine release also occurs when Ca++ is added after PS in the absence of antigen to the sensitized cells suspended in Ca++-free medium. Unlike the antigen-induced release, the intensity of this non-antigen-induced release varies depending on both mast-cell and antiserum pools. A heat-labile factor(s, which is different from antigen-specific IgE antibody and is also contained in normal mouse serum, is involved in this reaction. In the antigen-nondependent (PS + Ca++-induced release, no decay in the responsiveness to Ca++ is observed after PS addition. Both the antigen-induced and non-antigen-induced release are completed fairly rapidly and are dependent of temperature, pH and energy.

  9. Are basophil histamine release and high affinity IgE receptor expression involved in asymptomatic skin sensitization?

    DEFF Research Database (Denmark)

    Jensen, Bettina Margrethe; Assing, K; Jensen, Lone Hummelshøj

    2006-01-01

    . However, a relationship between the AS status and FcepsilonRI has not been investigated. We aimed to characterize basophils from AS by looking at histamine release (HR) (sensitivity and reactivity) and the FcepsilonRI molecule, and compare it with nonatopic (NA) or allergic (A) persons....

  10. 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.

  11. 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...

  12. Suppression of basophil histamine release and other IgE-dependent responses in childhood Schistosoma mansoni/hookworm coinfection

    DEFF Research Database (Denmark)

    Pinot de Moira, Angela; Fitzsimmons, Colin M; Jones, Frances M;

    2014-01-01

    in Ugandan schoolchildren coinfected with Schistosoma mansoni and hookworm. METHODS: Skin prick test (SPT) sensitivity to house dust mite allergen (HDM) and current wheeze were assessed pre-anthelmintic treatment. Nonspecific (anti-IgE), helminth-specific, and HDM-allergen-specific basophil histamine release...

  13. Involvement of presynaptic H3 receptors in the inhibitory effect of histamine on serotonin release in the rat brain cortex.

    Science.gov (United States)

    Fink, K; Schlicker, E; Neise, A; Göthert, M

    1990-11-01

    Rat brain cortex slices or synaptosomes preincubated with 3H-serotonin were superfused with physiological salt solution (which, in the case of slices, contained citalopram, an inhibitor of serotonin uptake), and the effects of histamine and related drugs on the evoked tritium overflow were studied. The electrically (3 Hz) evoked tritium overflow from slices was inhibited by histamine and the H3 receptor agonists R-(-)-alpha-methylhistamine and N alpha-methylhistamine (pIC12.5 values: 6.41, 7.28 and 6.12, respectively), but not affected by the H1 receptor agonist 2-(2-thiazolyl)ethylamine and the H2 receptor agonist dimaprit (each at 10 mumol/l). The concentration-response curve for histamine was shifted to the right by the H3 receptor antagonists impromidine, burimamide and thioperamide (apparent pA2 values: 7.45, 5.97 and 7.88, respectively); the concentration-response curve of serotonin for its inhibitory effect on the electrically evoked overflow was not affected by the three drugs (apparent pA2 values: less than 5.5, less than 5.5 and less than 6.5). Given alone, impromidine, thioperamide and a low concentration of burimamide facilitated the electrically evoked overflow. In slices superfused with K(+)-rich, Ca2(+)-free solution containing tetrodotoxin throughout and in synaptosomes superfused with Ca2(+)-free solution, histamine inhibited the overflow evoked by introduction of Ca2+ (in synaptosomes, simultaneously with an increased amount of K+). In either tissue, the effect of histamine was counteracted by thioperamide. The results provide evidence that exogenous and probably also endogenous histamine inhibits serotonin release in the rat brain cortex via presynaptic histamine H3 receptors.

  14. Acute stress modulates the histamine content of mast cells in the gastrointestinal tract through interleukin-1 and corticotropin-releasing factor release in rats.

    Science.gov (United States)

    Eutamene, Helene; Theodorou, Vassilia; Fioramonti, Jean; Bueno, Lionel

    2003-12-15

    Stress results in activation of the hypothalamic pituitary adrenal axis and affects illnesses such as neuroinflammatory syndrome. In vivo acute stress (restraint stress) induces gastrointestinal function disturbances through colonic mast cell activation. This study investigated the effect of acute stress in histamine content of colonic mast cells, and the central role of interleukin-1 (IL-1) and corticotropin-releasing factor (CRF) in this effect. After a restraint stress session colonic segments were isolated and submitted to three protocols: (i) determination of histamine levels by radioimmunoassay (RIA) after incubation with 48/80 compound, (ii) evaluation by histology of mucosal mast cell (MMC) number and (iii) determination of histamine immunoreactivity of MMC. These procedures were conducted (1) in sham or stressed rats, (2) in stressed rats previously treated with intracerebroventricular (I.C.V.) IL-1ra or alpha-helical CRF9-41, (3) in naive rats pretreated with I.C.V. rhIL-1beta or CRF and (4) in rats treated with central IL-1beta and CRF plus alpha-helical CRF and IL-1ra, respectively (cross-antagonism reaction). Acute stress increases histamine content in colonic mast cells, without degranulation. I.C.V. pretreatment with IL-1ra or alpha-helical CRF9-41 blocked stress-induced mast cell histamine content increase. Both I.C.V. rhIL-1beta and CRF injections reproduced the stress-linked changes. I.C.V. treatment with CRF antagonist blocked I.C.V. rhIL-1beta-induced mast cell histamine content increase, whereas central IL-1ra did not affect stress events induced by I.C.V. CRF administration. These results suggest that in rats acute stress increases colonic mast cell histamine content. This effect is mediated by the release in cascade in the brain first of IL-1 and secondly of CRF.

  15. Histamine released from epidermal keratinocytes plays a role in α-melanocyte-stimulating hormone-induced itching in mice.

    Science.gov (United States)

    Shimizu, Kyoko; Andoh, Tsugunobu; Yoshihisa, Yoko; Shimizu, Tadamichi

    2015-11-01

    Sunburn, wound repair, and chronic renal failure with hemodialysis are usually accompanied by both pigmentation and itching. Proopiomelanocortin-derived α-melanocyte-stimulating hormone (α-MSH) is produced in response to external stimuli, such as UV irradiation, and is involved in cutaneous pigmentation. However, it is unclear whether α-MSH is also involved in the itching. We therefore investigated whether α-MSH elicited itch-related responses in mice. We found that an intradermal injection of α-MSH induced hind-paw scratching, an itch-related response, in mice. The α-MSH-induced scratching was inhibited by the μ-opioid receptor antagonist naltrexone and the H1 histamine receptor antagonist terfenadine. In mast cell-deficient mice, α-MSH also elicited scratching, which was inhibited by terfenadine. The immunoreactivity for l-histidine decarboxylase, a key enzyme required for the production of histamine, histamine, and the melanocortin 1 and 5 receptors were shown in not only mast cells but also keratinocytes in murine skin. In addition to the expression of l-histidine decarboxylase and melanocortin 1 and 5 receptors, the mouse keratinocyte cell lines (Pam212) also showed immunoreactivity for l-histidine decarboxylase, histamine, and melanocortin 1 and 5 receptors. The application of α-MSH induced the release of histamine from Pam212 cells. These findings indicate that α-MSH may play an important role in the itching associated with pigmented cutaneous lesions and that the histamine released from keratinocytes is involved in this α-MSH-induced itching.

  16. Evidence of NK1 and NK2 Tachykinin Receptors and their Involvement in Histamine Release in a Murine Mast Cell Line

    Science.gov (United States)

    1992-01-01

    Binding of 3H substance P (SP) and histamine release were examined using a cloned mouse mast cell line. SP binding was saturable and specific. In the...Although the results suggest the coexistence of functional NK1 and NK2 receptors, it appears that in this mast cell line neurokinin-induced histamine

  17. Histamine release from basophil leukocytes in asthma patients after in vitro provocation with various neuromuscular blocking drugs and intravenous anaesthetic agents

    DEFF Research Database (Denmark)

    Guldager, H; Søndergaard, I

    1987-01-01

    Basophil histamine release is a relatively new investigation technique, which can be used in the diagnosis of anaphylactoid reactions. Our aim in this investigation was to determine reference values for asthma patients and normal subjects. Blood from eight asthmatic patients and eight normal...... subjects was tested for histamine release after in vitro provocation with various neuromuscular blocking drugs and intravenous anaesthetic agents. There was significantly higher histamine release for asthmatic patients than for normal subjects, P less than 0.001 (analysis of variance). This had no effect...

  18. 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.

  19. 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

    The ATP content of rat peritoneal mast cells has been studied in relation to histamine release induced by compound 48/80 and antigen-antibody (anaphylactic) reaction in vitro. When the ATP content of actively sensitized mast cells was reduced to different levels by oligomycin, a good correlation...... was obtained between the ATP levels and the amounts of histamine released by the anaphylactic reaction. A similar linear relation has previously been demonstrated between the ATP levels of mast cells and histamine release induced by compound 48/80. The ATP content of mast cells was also studied at different...... intervals after the exposure of the cells to antigen or compound 48/80. No significant change in the ATP content was observed in untreated mast cells during the short period when histamine release occurs. If, however, the mast cells were preincubated with oligomycin or 2-deoxyglucose to reduce the rate...

  20. Histamine release-neutralization assay for sera of patients with atopic dermatitis and/or cholinergic urticaria is useful to screen type I hypersensitivity against sweat antigens.

    Science.gov (United States)

    Shindo, Hajime; Ishii, Kaori; Yanase, Yuhki; Suzuki, Hidenori; Hide, Michihiro

    2012-10-01

    We previously reported that about 80 % of patients with atopic dermatitis and 60 % with cholinergic urticaria revealed type I allergy against sweat, by means of skin test against autologous sweat and/or histamine-release test for peripheral blood basophils with semi-purified sweat antigen. In this study, we developed an assay for sera to neutralize histamine-releasing activity of semi-purified sweat antigen. The semi-purified sweat antigen was pre-incubated with serially diluted sera for 30 min at 37 °C and was subjected to histamine-release activity. Histamine release-neutralization (HRN) activities were calculated by measuring the amount of histamine release from basophils in the presence or absence of semi-purified sweat antigen. Of 62 subjects, 39 showed positive histamine release (≥5 %) from their basophils in response to semi-purified sweat antigen, and sera of 34 out of 39 subjects (87.2 %) were also positive in HRN activity (≥10 %). The specificity of the HRN assay was 0.522. Moreover, HRN activities in sera were largely correlated with degrees of histamine release from peripheral blood basophils of the same donors in response to sweat antigen. To identify the substance that neutralizes histamine-release activity, we removed IgE and IgG from the sera of HRN (+) subjects by column chromatography. The HRN activities in 30 out of 42 sera were largely reduced by the removal of IgG. On the other hand, sera of four subjects lost HRN activity by the removal of IgE, suggesting that the majority of HRN (+) subjects have serum IgG against the sweat antigen as well as IgE bound to peripheral basophils. Thus, the HRN assay maybe useful for the screening of type I allergy against sweat antigen.

  1. Effects of intracerebroventricular injection of histamine and related compounds on corticosterone release in rats.

    OpenAIRE

    Tsujimoto, S.; Okumura, Y.; Kamei, C.; Tasaka, K.

    1993-01-01

    1. The effects of intracerebroventricular (i.c.v.) injection of histamine and related compounds on plasma adrenocorticotrophic hormone (ACTH) and corticosterone concentrations were studied in conscious rats. 2. Histamine at doses of 5-20 micrograms kg-1 rapidly increased plasma ACTH and corticosterone concentrations almost simultaneously, and subsequent courses were also similar to each other. However, in the case of CRF-41 (i.v.), the plasma ACTH concentration first increased followed by an ...

  2. The molecular and biological analysis of ixodid ticks histamine release factors.

    Science.gov (United States)

    Mulenga, Albert; Azad, Abdu F

    2005-01-01

    We previously described a Dermacentor varibialis (DV) cDNA that encodes a ubiquitously expressed and tick saliva-secreted functional histamine release factor (HRF) homolog. In this study gene specific primers based on DVHRF open reading frame nucleotide sequence were utilized to amplify three orthologs, from the wood tick, D. andersoni (DA), the black legged tick, the southern cattle tick, Boophilus microplus (BM) and the lone star tick, Amblyomma americanum (AA). At nucleotide level, sequence comparisons revealed 98 89 and 84% similarity to DVHRF for DAHRF, AAHRF and BMHRF, respectively, while predicted polypeptide comparisons revealed 98, 96 and 91% similarity for DAHRF, AAHRF and BMHRF respectively. Phylogenetically, the tick HRF clade, while distinct (100% bootstrap value), is closely related to other arthropods, but distantly related to vertebrate and protozoan clades. Consistent with sequence similarity analysis, a DVHRF-specific northern blotting probe hybridized a approximately 900 base pair (bp) mRNA band on all RNA blots. Likewise a mouse polyclonal antibody to E. coli-expressed recombinant (r) DVHRF, cross-reacted baculovirus-expressed non-fusion rAAHRF, rDAHRF, and rBMHRF. As revealed by northern blotting analysis of larvae and nymph RNA, DVHRF mRNA is expressed in both immature and mature ticks indicating that its transcription is not developmentally regulated. Unlike rHRF/TCTP proteins of other organisms, the calcium-binding function may not be conserved for tick HRF homologs as revealed by the 45CaCl2+ overlay assay. Apparent global expression of DVHRF and its orthologs make this protein family an ideal target antigen for development of novel tick control strategies targeting multiple tick species.

  3. Tick saliva increases production of three chemokines including monocyte chemoattractant protein-1, a histamine-releasing cytokine.

    Science.gov (United States)

    Langhansová, H; Bopp, T; Schmitt, E; Kopecký, J

    2015-02-01

    The effect of Ixodes ricinus tick saliva on the production of various cytokines and chemokines by mouse splenocytes was tested by a cytokine array. We demonstrated a strong upregulation of three chemokines, monocyte chemoattractant protein-1 (MCP-1), thymus-derived chemotactic agent 3 (TCA-3) and macrophage inflammatory protein 2 (MIP-2). MCP-1 could be induced by tick saliva itself. While TCA-3 and MIP-2 are engaged in Th2 polarization of the host immune response associated with tick feeding, MCP-1 may act as a histamine release factor, increasing blood flow into the feeding lesion thus facilitating tick engorgement in the late, rapid feeding phase.

  4. Inhibition by amiloride and by Na-depletion of A23187-stimulated arachidonic acid and histamine release from rat mast cells

    DEFF Research Database (Denmark)

    Linnebjerg, H.; Hansen, Harald S.; Jensen, B.

    1988-01-01

    Rat peritoneal mast cells, labelled with [C]arachidonic acid, released histamine and [C]arachidonic acid upon the addition of A23187. The release induced by low concentrations of A23187 was suppressed by removal of extracellular Na and by addition of the Na/H exchange inhibitor, amiloride. Addition...

  5. Synergism between thapsigargin and the phorbol ester 12-O-tetradecanoylphorbol 13-acetate on the release of [C]arachidonic acid and histamine from rat peritoneal mast cells

    DEFF Research Database (Denmark)

    Jacobsen, S.; Hansen, Harald S.; Jensen, B.

    1987-01-01

    Thapsigargin is a potent skin irritating sesquiterpene lactone isolated from the roots of Thapsia garganica L. (Apiaceae). In rat peritoneal mast cells thapsigargin induced a calcium-dependent non-cytotoxic [C]arachidonic acid and histamine release. A minor amount of the released [C...

  6. [Cerebral ischemia and histamine].

    Science.gov (United States)

    Adachi, Naoto

    2002-10-01

    Cerebral ischemia induces excess release of glutamate and an increase in the intracellular Ca2+ concentration, which provoke catastrophic enzymatic processes leading to irreversible neuronal injury. Histamine plays the role of neurotransmitter in the central nervous system, and histaminergic fibers are widely distributed in the brain. In cerebral ischemia, release of histamine from nerve endings has been shown to be enhanced by facilitation of its activity. An inhibition of the histaminergic activity in ischemia aggravates the histologic outcome. In contrast, intracerebroventricular administration of histamine improves the aggravation, whereas blockade of histamine H2 receptors aggravates ischemic injury. Furthermore, H2 blockade enhances ischemic release of glutamate and dopamine. These findings suggest that central histamine provides beneficial effects against ischemic neuronal damage by suppressing release of excitatory neurotransmitters. However, histaminergic H2 action facilitates the permeability of the blood-brain barrier and shows deleterious effects on cerebral edema.

  7. Development and validation of a liquid-chromatography tandem mass spectrometry method to determine in vitro and in vivo histamine release.

    Science.gov (United States)

    Chimalakonda, Krishna C; Pang, Eric; Weaver, James L; Howard, Kristina E; Patel, Vikram; Boyne, Michael T

    2015-01-01

    Histamine is an important biogenic amine involved in regulating numerous physiological and pathophysiological processes in humans and animals. To date, there have been very few studies focused on developing and validating sensitive liquid-chromatography-tandem mass spectrometric (LC-MS/MS) assays capable of quantitative trace level histamine analysis in biological matrices. In the present study, a rapid and sensitive LC-MS/MS assay, amenable to high throughput analysis was developed and validated to characterize in vitro and in vivo histamine release. The LC-MS/MS procedure incorporating deuterium labeled internal standards provides rapid resolution of histamine with excellent sensitivity, precision, and accuracy. Histamine eluted at 1.5 min and was well separated from endogenous plasma peaks. The total run time of the assay was 8.0 min. A linear (r(2) ≥ 0.99) instrument response over the entire concentration range of 1.0-1000 ng/mL was observed. Excellent accuracy (error ± 3.4%) and precision (CV ± 10%) of the assay was demonstrated, with the lower limit of quantitation (LLOQ) at 15.6 ng/mL. The validated LC-MS/MS assay was applied to determine histamine release in both in vitro and in vivo models. Peritoneal mast cells treated with prototypical degranulating agents (Compound 48/80 and Teicoplanin) showed that the two chemicals caused approximately 40% histamine release. In rats, using this assay, basal histamine plasma levels were typically under 100 ng/mL. Treatment with an agent suspected of causing anaphylactic type reactions resulted in plasma histamine levels to increase above 3000 ng/mL. The LC-MS/MS assay presented in this study can be applied to further characterize the physiological and pathophysiological role of histamine release in complex in vitro and in vivo models. Importantly, the LC-MS/MS assay may be useful in assessing active pharmaceutical ingredient-mediated degranulation and anaphylaxis as part of either a pre-market or a post

  8. Effects of palmitoylethanolamide on immunologically induced histamine, PGD2 and TNFalpha release from canine skin mast cells.

    Science.gov (United States)

    Cerrato, S; Brazis, P; della Valle, M F; Miolo, A; Puigdemont, A

    2010-01-15

    Palmitoylethanolamide (PEA) is an endocannabinoid-like compound and the parent molecule of the aliamide family, a group of fatty acid amides able to act through the down-regulation of mast cell degranulation. PEA has been proven to exert both analgesic and anti-inflammatory activity, and recent studies have shown its ability in reducing clinical symptoms of inflammatory skin diseases, both in humans and in animals. Although its pharmacological efficacy is well known, the mechanism of action of this family of compounds is still unclear. To better understand the cellular effects of aliamides in dogs, canine mast cells freshly isolated from skin biopsies were incubated with IgE-rich serum and were challenged with anti-canine IgE. Histamine, prostaglandin D(2) (PGD(2)) and tumour necrosis factor-alpha (TNFalpha) release was measured in the presence and absence of increasing concentrations of PEA, ranging from 10(-8)M to 10(-5)M. Histamine, PGD(2) and TNFalpha release, immunologically induced by canine anti-IgE, were significantly inhibited in the presence of PEA. The maximum inhibitory effect on histamine release was observed at 3x10(-6)M PEA concentration achieving an inhibition of 54.3+/-5.2%. PGD(2) release was significantly inhibited at 10(-5)M and 10(-6)M PEA concentrations with 25.5+/-10.2% and 14.6+/-5.6% of inhibition, respectively. Finally, PEA inhibited TNFalpha release to 29.2+/-2.0% and 22.1+/-7.2%, at concentrations of 10(-5)M and 3x10(-6)M, respectively. The results obtained in the present study showed the ability of the aliamide PEA to down-modulate skin mast cell activation. Therefore, our findings suggest that the beneficial effect of PEA, observed in inflammation and pain clinical studies, could be due, at least in part, to its ability to inhibit the release of both preformed and newly synthesised mast cell mediators.

  9. The Effects of a Chactoid Scorpion Venom and Its Purified Toxins on Rat Blood Pressure and Mast Cells Histamine Release

    Directory of Open Access Journals (Sweden)

    Philip Lazarovici

    2013-07-01

    Full Text Available The effect of the venom of the Chactoid family of scorpions on blood pressure was scantly investigated and was addressed in the present study using the venom of the Israeli scorpion, Scorpio maurus palmatus. Blood pressure in rats was monitored via cannulated femoral artery, while venom and toxins were introduced into femoral vein. Venom injection elicited a biphasic effect, expressed first by a fast and transient hypotensive response, which lasted up to 10 min, followed by a hypertensive response, which lasted up to one hour. It was found that these effects resulted from different venom components. Phospholipase A2 produced the hypotensive effect, while a non-enzymatic neurotoxic polypeptide fraction produced the hypertensive effect. Surprisingly, the main neurotoxic polypeptide to mice had no effect on blood pressure. In vitro experiments indicated that the hypertensive factors caused histamine release from the peritoneal mast cells, but this effect is assumed to be not relevant to their in vivo effect. In spite of the cytotoxic activity of phospholipase A2, it did not release histamine. These findings suggest that the effects of venom and isolated fractions on blood pressure parameters are mediated by different mechanisms, which deserve further pharmacological investigation.

  10. The effects of a chactoid scorpion venom and its purified toxins on rat blood pressure and mast cells histamine release.

    Science.gov (United States)

    Ettinger, Keren; Cohen, Gadi; Momic, Tatjana; Lazarovici, Philip

    2013-07-29

    The effect of the venom of the Chactoid family of scorpions on blood pressure was scantly investigated and was addressed in the present study using the venom of the Israeli scorpion, Scorpio maurus palmatus. Blood pressure in rats was monitored via cannulated femoral artery, while venom and toxins were introduced into femoral vein. Venom injection elicited a biphasic effect, expressed first by a fast and transient hypotensive response, which lasted up to 10 min, followed by a hypertensive response, which lasted up to one hour. It was found that these effects resulted from different venom components. Phospholipase A₂ produced the hypotensive effect, while a non-enzymatic neurotoxic polypeptide fraction produced the hypertensive effect. Surprisingly, the main neurotoxic polypeptide to mice had no effect on blood pressure. In vitro experiments indicated that the hypertensive factors caused histamine release from the peritoneal mast cells, but this effect is assumed to be not relevant to their in vivo effect. In spite of the cytotoxic activity of phospholipase A₂, it did not release histamine. These findings suggest that the effects of venom and isolated fractions on blood pressure parameters are mediated by different mechanisms, which deserve further pharmacological investigation.

  11. Use of a new glass microfibre histamine release method to study the modulation of the host response in human schistosomiasis mansoni. Individuals with different degrees of exposure to the disease show differing antibody biological function

    DEFF Research Database (Denmark)

    Satti, M.Z.; Ebbesen, F.; Vennervald, B.;

    1996-01-01

    A new glass microfibre histamine release method was used to study the modulation of the host response in human schistosomiasis mansoni to improve our understanding of the role of basophils in the development of immunity in schistosomiasis mansoni. The histamine release from umbilical cord blood b...... basophils sensitized with sera from Sudanese individuals infected with Schistosoma mansoni was measured. Schistosomiasis sera (n=113) were able to passively sensitize basophils and induce a positive histamine release in response to whole worm homogenate (WWH)(chi(2)=40.5, P......A new glass microfibre histamine release method was used to study the modulation of the host response in human schistosomiasis mansoni to improve our understanding of the role of basophils in the development of immunity in schistosomiasis mansoni. The histamine release from umbilical cord blood...

  12. Neuronal histamine decreases fat accumulation and up-regulates UCP family in db/db obese mice

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    To examine anti-obesity and-diabetic effects of neuronal histamine especially in leptin resistant states, we investigated the effects of chronic central treatment with histamine on lipid, glucose and energy metabolism of db/db obese mice, which are genetically leptin receptor mutated mice. Chronic centrally treatment with histamine (0.05 μmol*g-1 body weight*d-1 for 7 days) decreased body weight, food intake in db/db obese mice, and decreased body fat weight, serum concentration of glucose compared with pair-fed db/db obese mice. Neuronal histamine also suppressed ob mRNA in the white adipose tissue (WAT), serum leptin and increased UCPs mRNA expression in brown adipose tissue (BAT) and in WAT compared with pair-fed controls. These above effects of the histamine were attenuated in these mice with combination of targeted disruption of the histamine H1 receptor gene. In conclusion, neuronal histamine can regulate body fat deposition, serum glucose, leptin, BAT and WAT UCPs expression even in leptin insensitive db/db obese mice.

  13. Changes in IgE- and Antigen-dependent histamine-release in peripheral blood of Schistosoma mansoni-infected Ugandan fishermen after treatment with praziquantel

    Directory of Open Access Journals (Sweden)

    Kazibwe Francis

    2004-04-01

    Full Text Available Abstract Background Parasite-specific IgE levels correlate with human resistance to reinfection with Schistosoma spp. after chemotherapy. Although the role of eosinophils in schistosomiasis has been the focus of a great deal of important research, the involvement of other Fcε receptor-bearing cells, such as mast cells and basophils, has not been investigated in relation to human immunity to schistosomes. Chemotherapy with praziquantel (PZQ kills schistosomes living in an in vivo blood environment rich in IgE, eosinophils and basophils. This releases parasite Ags that have the potential to cross-link cell-bound IgE. However, systemic hypersensitivity reactions are not induced by treatment. Here, we describe the effects of schistosomiasis, and its treatment, on human basophil function by following changes in total cellular histamine and in vitro histamine-release induced by schistosome Ags or anti-IgE, in blood samples from infected Ugandan fishermen, who are continuously exposed to S. mansoni infection, before and 1-day and 21-days after PZQ treatment. Results There was a significant increase in the total cellular histamine in blood samples at 1-day post-treatment, followed by a very significant further increase by 21-days post-treatment. In vitro histamine-release induced by S. mansoni egg (SEA or worm (SWA Ags or anti-IgE antibody, was significantly reduced 1-day post-treatment. The degree of this reduction correlated with pre-treatment infection intensity. Twenty-1-days post-treatment, SEA-induced histamine-release was still significantly lower than at pretreatment. Histamine-release was not correlated to plasma concentrations of total or parasite-specific IgE, nor to specific IgG4 plasma concentrations. Conclusion The biology of human blood basophils is modulated by S. mansoni infection and praziquantel treatment. Infection intensity-dependent suppression of basophil histamine-release, histamine-dependent resistance to infection, and

  14. Central infusion of histamine reduces fat accumulation and upregulates UCP family in leptin-resistant obese mice.

    Science.gov (United States)

    Masaki, T; Yoshimatsu, H; Chiba, S; Watanabe, T; Sakata, T

    2001-02-01

    Leptin resistance has recently been confirmed not only in animal obese models but in human obesity. Evidence is rapidly emerging that suggests that activation of histamine signaling in the hypothalamus may have substantial anti-obesity and antidiabetic actions, particularly in leptin-resistant states. To address this issue, effects of central, chronic treatment with histamine on food intake, adiposity, and energy expenditure were examined using leptin-resistant obese and diabetic mice. Infusion of histamine (0.05 pmol x g body wt(-1) x day(-1)) into the lateral cerebroventricle (i.c.v.) for 7 successive days reduced food intake and body weight significantly in both diet-induced obesity (DIO) and db/db mice. Histamine treatment reduced body fat weight, ob gene expression, and serum leptin concentration more in the model mice than in pair-fed controls. The suppressive effect on fat deposition was significant in visceral fat but not in subcutaneous fat. Serum concentrations of glucose and/or insulin were reduced, and tests for glucose and insulin tolerance showed improvement of insulin sensitivity in those mice treated with histamine compared with pair-fed controls. On the other hand, gene expression of uncoupling protein (UCP)-1 in brown adipose tissue and UCP-3 expression in white adipose tissue were upregulated more in mice with i.c.v. histamine infusion than in the pair-fed controls. These upregulating effects of histamine were attenuated by targeted disruption of the H1-receptor in DIO and db/db mice. Sustained i.c.v. treatment with histamine thus makes it possible to partially restore the distorted energy intake and expenditure in leptin-resistant mice. Together, i.c.v. treatment with histamine contributes to improvement of energy balance even in leptin-resistant DIO and db/db mice.

  15. Histamine H3 receptor-mediated inhibition of noradrenaline release in pig retina discs.

    Science.gov (United States)

    Schlicker, E; Schunack, W; Göthert, M

    1990-11-01

    Discs of pig retina were preincubated with 3H-noradrenaline, 3H-dopamine or 3H-serotonin and then superfused. Electrical field stimulation increased the outflow of tritium from discs preincubated with 3H-noradrenaline or 3H-dopamine, but no from discs preincubated with 3H-serotonin. The tritium content at the end of superfusion was similar in discs preincubated with 3H-noradrenaline or 3H-dopamine but about tenfold lower in discs preincubated with 3H-serotonin. The tritium content in discs preincubated with 3H-noradrenaline was markedly reduced when desipramine was present during preincubation but was not affected by selective inhibitors of dopamine and serotonin uptake. The tritium content in discs preincubated with 3H-dopamine and 3H-serotonin, in contrast, was reduced or tended to be reduced by a selective dopamine and serotonin uptake inhibitor, respectively. The electrically evoked overflow of tritium from discs preincubated with 3H-noradrenaline was abolished by tetrodotoxin or omission of Ca2+. In discs superfused with desipramine, the electrically evoked overflow was enhanced by phentolamine but not affected by histamine. When both desipramine and phentolamine were present in the superfusion medium, histamine inhibited the evoked overflow (pIC15 6.85). This effect was mimicked by the histamine H3 receptor agonist R-(-)-alpha-methylhistamine as well as by its S-(+)-enantiomer (pIC15 7.85 and 5.30, respectively) but not by the H1 receptor agonist 2-(2-thiazolyl)ethylamine and the H2 receptor agonist dimaprit (each 10 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Porcine mast cells infected with H1N1 influenza virus release histamine and inflammatory cytokines and chemokines.

    Science.gov (United States)

    Lee, In Hong; Kim, Hyun Soo; Seo, Sang Heui

    2017-04-01

    Mast cells reside in many tissues, including the lungs, and might play a role in enhancing influenza virus infections in animals. In this study, we cultured porcine mast cells from porcine bone marrow cells with IL-3 and stem cell factor to study the infectivity and activation of the 2009 pandemic H1N1 influenza virus of swine origin. Porcine mast cells were infected with H1N1 influenza virus, without the subsequent production of infectious viruses but were activated, as indicated by the release of histamines. Inflammatory cytokine- and chemokine-encoding genes, including IL-1α, IL-6, CXCL9, CXCL10, and CXCL11, were upregulated in the infected porcine mast cells. Our results suggest that mast cells could be involved in enhancing influenza-virus-mediated disease in infected animals.

  17. Studies on the release of leukotrienes and histamine by human lung parenchymal and bronchial fragments upon immunologic and nonimmunologic stimulation. Effects of nordihydroguaiaretic acid, aspirin, and sodium cromoglycate

    Science.gov (United States)

    1985-01-01

    Fragments of human lung parenchyma or bronchi were studied by high performance liquid chromatography, gas chromatography-mass spectrometry, and bioassay for the biosynthesis of 5-lipoxygenase metabolites of arachidonic acid, and by radioenzymatic assay for the release of histamine, upon immunologic and nonimmunologic stimulation. Human lung parenchyma were passively sensitized with serum from timothy- positive allergic patients (radioallergosorbent test, 30-40%) and challenged with 0.5 microgram/ml of timothy allergen. Analysis of the incubation media showed the presence of LTB4, LTC4, LTD4, LTE4, and histamine. Maximum release of LTB4 and LTD4 was observed after 15 min of challenge (92.8 +/- 21, and 67.8 +/- 14 pmol/g tissue wet weight, respectively; mean +/- SEM) whereas maximum release of LTC4 was observed after 5 min of challenge (25 +/- 7.1 pmol). In parallel to leukotriene formation, histamine was released rapidly and reached a maximum after approximately 15 min of challenge (2.85 +/- 0.76 nmol/g tissue). When fragments of human lung parenchyma were stimulated with ionophore A23187 (4 microM), we observed a profile of leukotriene and histamine release similar to that seen in response to the allergen. Ionophore A23187 stimulated the release of two- to fivefold greater amounts of leukotrienes and histamine than did the allergen. Release of LTC4 and histamine was maximal after 5 min of stimulation (83 +/- 22.2 and 5.2 +/- 0.95 nmol/g tissue, respectively), whereas LTB4 and LTD4 release reached a maximum after 15 min (438 +/- 66.6 and 205 +/- 68 nmol/g tissue, respectively). In addition, human lung parenchyma metabolized LTB4 into omega-OH-LTB4 and omega-COOH-LTB4. This tissue also released 5-hydroxy-eicosatetraenoic acid (5-Hete), 12-Hete, and 15- Hete. Fragments of human lung bronchi also released a similar profile of leukotrienes (except LTC4) and histamine when challenged with the allergen or ionophore A23187. Maximum release of LTB4 and LTD4 by allergen or

  18. Radiation-released histamine in the rhesus monkey as modified by mast cell depletion and antihistamine. Scientific report

    Energy Technology Data Exchange (ETDEWEB)

    Doyle, T.F.; Strike, T.A.

    1975-06-01

    Changes in blood histamine concentrations of rhesus monkeys were measured after a 4000-rad dose of mixed gamma-neutron radiation. All animals were pretreated with amino-guanidine to retard histamine catabolism. Histamine concentrations increased from 26 + or - 13.5 to 235 + or - 16 ng/ml after irradiation. When the animals were pretreated with an antihistamine, chlorpheniramine (3 mg/kg), histamine concentrations changed from 25.7 + or - 13.5 to 462 + or - 226 ng/ml after irradiation. When the monkeys were pretreated with a specific mast cell histamine depleter, compound 48/80 (1mg/kg per day) for four consecutive days and then irradiated (4000 rads), histamine concentrations did not change significantly. When 48/80 was given 20 min after irradiation, histamine concentrations changed from 18 + or - 2 ng/ml to a maximum of 35 + or - 9 ng/ml after 48/80 injection. (Author) (GRA)

  19. Analysis of the effect of a 60 Hz AC field on histamine release by rat peritoneal mast cells.

    Science.gov (United States)

    Price, J A; Strattan, R D

    1998-01-01

    Reports have indicated effects of electromagnetic fields on inflammatory processes in vivo. To begin a systematic approach toward separating and examining the many components of such responses, we created and tested a temperature-controlled device to develop 5 mT 60 Hz magnetic fields for studies of the effects of fields on mast cells, a key component in acute inflammatory responses. Such fields have been reported to modulate cell activity, including changes in membrane function, in various systems. The magnetic field was generated using a solenoid and calibrated with an induction probe. Tests of mast cell function were determined by histamine release response to stimulation by compound 48/80, using both an "expose then test" and a "test during exposure" protocol. Aliquots not treated with 48/80 were used to evaluate field treatment effects on spontaneous histamine release. Freshly harvested rat peritoneal mast cells were exposed to the magnetic field for periods of 30 min to 2 h at 37 degrees C. They showed no significant degranulation during treatment, nor did they show reduced sensitivity to the degranulating agent 48/80. These observations are consistent with a model in which such processes are exclusively reflexive by the cells using field-independent membrane systems. This observation is very useful and was needed before examining longer term exposures in which gene expression in the cells might be influenced; this is the first such report of in vitro exposure of purified mast cells under these conditions and will further the study of the effects of electromagnetic fields on cell types active in acute inflammation.

  20. Controlled-release formulation of antihistamine based on cetirizine zinc-layered hydroxide nanocomposites and its effect on histamine release from basophilic leukemia (RBL-2H3 cells

    Directory of Open Access Journals (Sweden)

    Hussein Al Ali SH

    2012-07-01

    Full Text Available Samer Hasan Hussein Al Ali,1 Mothanna Al-Qubaisi,2 Mohd Zobir Hussein,1,3 Maznah Ismail,2,4 Zulkarnain Zainal,1 Muhammad Nazrul Hakim51Department of Chemistry, Faculty of Science, 2Laboratory of Molecular Biomedicine, Institute of Bioscience, 3Advanced Materials and Nanotechnology Laboratory, Institute of Advanced Technology (ITMA, 4Department of Nutrition and Dietetics, Faculty of Medicine and Health Science, Universiti Putra, Malaysia; 5Department of Biomedical Science, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Selangor, MalaysiaAbstract: A controlled-release formulation of an antihistamine, cetirizine, was synthesized using zinc-layered hydroxide as the host and cetirizine as the guest. The resulting well-ordered nanolayered structure, a cetirizine nanocomposite "CETN," had a basal spacing of 33.9 Å, averaged from six harmonics observed from X-ray diffraction. The guest, cetirizine, was arranged in a horizontal bilayer between the zinc-layered hydroxide (ZLH inorganic interlayers. Fourier transform infrared spectroscopy studies indicated that the intercalation takes place without major change in the structure of the guest and that the thermal stability of the guest in the nanocomposites is markedly enhanced. The loading of the guest in the nanocomposites was estimated to be about 49.4% (w/w. The release study showed that about 96% of the guest could be released in 80 hours by phosphate buffer solution at pH 7.4 compared with about 97% in 73 hours at pH 4.8. It was found that release was governed by pseudo-second order kinetics. Release of histamine from rat basophilic leukemia cells was found to be more sensitive to the intercalated cetirizine in the CETN compared with its free counterpart, with inhibition of 56% and 29%, respectively, at 62.5 ng/mL. The cytotoxicity assay toward Chang liver cells line show the IC50 for CETN and ZLH are 617 and 670 µg/mL, respectively.Keywords: cetirizine hydrochloric acid

  1. In vitro histamine release from basophils of asthmatic and atopic individuals in D/sub 2/O

    Energy Technology Data Exchange (ETDEWEB)

    Tung, R.; Lichtenstein, L.M.

    1982-05-01

    It was found that spontaneous histamine release from human basophils in H/sub 2/O-based buffers is negligible; in D/sub 2/O-based buffers, however, release is observed with the cells of some donors. Analysis of this phenomenon revealed release from the basophils of 1 of 22 control individuals (5%), 15 of 47 patients with allergic rhinitis (32%), and 14 of 20 asthmatic patients (70%). The difference between both patient groups and controls and between atopics and asthmatics was highly significant. That D/sub 2/O release was not cytotoxic is suggested by the finding that 37/sup 0/ was optimal, with inhibition at 4/sup 0/C or 46/sup 0/C as well as by EDTA, 2-deoxyglucose, and dibromoacetophenone, an inhibitor of phospholipase A/sub 2/. The release mechanism was unusual in that dibutyryl cAMP and agonists that cause an increase in cAMP lead to no inhibition. No correlation was noted between the total serum IgE level (and thus the number of IgE receptors on the basophil surface) and the magnitude of D/sub 2/O release. No increase in D/sub 2/O release was observed in 17 ragweed-sensitive patients through a ragweed season. A unique property of D/sub 2/O release was the loss of reactivity by preincubating cells at 37/sup 0/C for 30 min before adding D/sub 2/O. Non-D/sub 2/O-reactive cells could be ''converted'' to D/sub 2/O-reactive cells by incubation with antigen in the whole blood phase during leukocyte isolation; these cells showed the same loss of releaseability at 37/sup 0/C and an inhibitor profile similar to D/sub 2/O-responsive cells from ragweed allergic or asthmatic patients. We suggest that D/sub 2/O-based buffers reveal, in atopic and asthmatic patients, in vivo basophil activation; whether this is due to IgE cross-links, to C split products, or to other stimuli is not yet clear.

  2. Anti-allergic cromones inhibit histamine and eicosanoid release from activated human and murine mast cells by releasing Annexin A1.

    Directory of Open Access Journals (Sweden)

    Samia Yazid

    Full Text Available BACKGROUND AND PURPOSE: Although the 'cromones' (di-sodium cromoglycate and sodium nedocromil are used to treat allergy and asthma, their 'mast cell stabilising' mechanism of pharmacological action has never been convincingly explained. Here, we investigate the hypothesis that these drugs act by stimulating the release of the anti-inflammatory protein Annexin-A1 (Anx-A1 from mast cells. EXPERIMENTAL APPROACH: We used biochemical and immuno-neutralisation techniques to investigate the mechanism by which cromones suppress histamine and eicosanoid release from cord-derived human mast cells (CDMCs or murine bone marrow-derived mast cells (BMDMCs from wild type and Anx-A1 null mice. KEY RESULTS: CDMCs activated by IgE-FcRε1 crosslinking, released histamine and prostaglandin (PG D2, which were inhibited (30-65% by 5 min pre-treatment with cromoglycate (10 nM or nedocromil (10 nM, as well as dexamethasone (2 nM and human recombinant Anx-A1 (1-10 nM. In CDMCs cromones potentiated (2-5 fold protein kinase C (PKC phosphorylation and Anx-A1 phosphorylation and secretion (3-5 fold. Incubation of CDMCs with a neutralising anti-Anx-A1 monoclonal antibody reversed the cromone inhibitory effect. Nedocromil (10 nM also inhibited (40-60% the release of mediators from murine bone marrow derived-mast cells from wild type mice activated by compound 48/80 and IgE-FcRε1 cross-linking, but were inactive in such cells when these were prepared from Anx-A1 null mice or when the neutralising anti-Anx-A1 antibody was present. CONCLUSIONS AND IMPLICATIONS: We conclude that stimulation of phosphorylation and secretion of Anx-A1 is an important component of inhibitory cromone actions on mast cells, which could explain their acute pharmacological actions in allergy. These findings also highlight a new pathway for reducing mediator release from these cells.

  3. Histamine release factor from Dermanyssus gallinae (De Geer): characterization and in vitro assessment as a protective antigen.

    Science.gov (United States)

    Bartley, Kathryn; Nisbet, Alasdair J; Offer, Jill E; Sparks, Nicholas H C; Wright, Harry W; Huntley, John F

    2009-03-01

    A cDNA encoding a 174-amino-acid orthologue of a tick histamine release factor (HRF) was identified from the haematophagous poultry red mite Dermanyssus gallinae. The predicted D. gallinae HRF protein (Dg-HRF-1) sequence is highly conserved with the tick HRFs (identity 52-54%) and to a lesser degree with translationally controlled tumour proteins (TCTP) from mammals and other invertebrates (range 38-47%). Phylogenetically, Dg-HRF-1 partitions with the tick HRF clade suggesting a shared linage and potentially similar function(s). A recombinant Dg-HRF-1 protein (rDg-HRF-1) was produced and shown to induce degranulation of rat peritoneal mast cells in vitro, confirming conservation of the histamine-releasing function in D. gallinae. Polyclonal antibodies were generated in rabbits and hens to rDg-HRF-1. Western blotting demonstrated that native Dg-HRF is a soluble protein and immunohistochemical staining of mite sections revealed that the distribution of Dg-HRF, although ubiquitous, is more common in mite reproductive, digestive and synganglion tissues. A survey of hens housed continuously in a mite-infested commercial poultry unit failed to identify IgY specific for recombinant or native Dg-HRF, indicating that Dg-HRF is not exposed to the host during infestation/feeding and may therefore have potential as a vaccine using the concealed antigen approach. To test the protective capability of rDg-HRF-1, fresh heparinised chicken blood was enriched with yolk-derived anti-Dg-HRF IgY antibodies and fed to semi-starved mites using an in vitro feeding system. A statistically significant increase in mortality was shown (P=0.004) in mites fed with anti-Dg-HRF IgY after just one blood meal. The work presented here demonstrates, to our knowledge for the first time, the feasibility of vaccinating hens with recombinant D. gallinae antigens to control mite infestation and the potential of rDg-HRF-1 as a vaccine antigen.

  4. Further observations on the utilization of adenosine triphosphate in rat mast cells during histamine release induced by the ionophore A23187

    DEFF Research Database (Denmark)

    Johansen, Torben

    1980-01-01

    1 The relation between A23187-induced histamine release and the energy metabolism of the rat mast cells has been studied. 2 Ethacrynic acid was used as an inhibitor of calcium-induced histamine release from mast cells primed with the ionophore A23187, and to study calcium-induced changes...... in the adenosine triphosphate (ATP) content and the rate of lactate production of A23187-primed mast cells. 3 Ethacrynic acid by itself decreased the rate of glycolytic ATP production. 4 By measurement of the ATP content and the lactate production of mast cells with or without secretory activity, the increased...... demand of energy for exocytosis was estimated to be equivalent to 0.14 pmol of ATP pr 10(3) mast cells....

  5. 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...

  6. Structure-activity relationship of a series of 17 parabens and related compounds for histamine release in rat peritoneal mast cells and skin allergic reaction in guinea pigs.

    Science.gov (United States)

    Uramaru, Naoto; Inoue, Toshio; Watanabe, Yoko; Shigematsu, Hidenari; Ohta, Shigeru; Kitamura, Shigeyuki

    2014-02-01

    Parabens, which are a homologous series of esters of p-hydroxybenzoic acid, have been used as preservatives in cosmetics, medicines and foods because of their antimicrobial activity. However, parabens in cosmetics have been suspected to cause allergic contact dermatitis. In this study, we examined paraben-induced histamine release from rat peritoneal mast cells and skin reaction in guinea pigs using a series of 17 parabens with different alcohol side chains, ranging from methylparaben to dodecylparaben. Octylparaben showed the greatest histamine release-inducing activity from mast cells, and the activity was decreased in shorter- and longer-side-chain parabens. Octyl benzoate, octyl o-hydroxybenzoate and phenyloctane caused no significant degranulation of mast cells, whereas octyl m-hydroxybenzoate, octyl p-hydroxybenzoate and octyl phenol induced concentration-related degranulation. Metabolites of these parabens (p-hydroxybenzoic acid and alcohols) did not show histamine release-inducing activity. In the guinea pig skin reaction test, heptylparaben induced a typical strong skin reaction, while butylparaben induced a typical weak skin reaction, and methylparaben and dodecylparaben were inactive. Metabolites of parabens (p-hydroxybenzoic acid and alcohols) were also inactive. These results indicate that interaction of parabens with rat mast cells requires a minimum length and adequate lipophilicity of the alkyl side chain. Since metabolites of parabens were inactive, parabens appear to be direct-acting allergens.

  7. Suppression of Basophil Histamine Release and Other IgE-dependent Responses in Childhood Schistosoma mansoni/hookworm Coinfection

    Science.gov (United States)

    Pinot de Moira, Angela; Fitzsimmons, Colin M.; Jones, Frances M.; Wilson, Shona; Cahen, Pierre; Tukahebwa, Edridah; Mpairwe, Harriet; Mwatha, Joseph K.; Bethony, Jeffrey M.; Skov, Per S.; Kabatereine, Narcis B.; Dunne, David W.

    2014-01-01

    Background. The poor correlation between allergen-specific immunoglobulin E (asIgE) and clinical signs of allergy in helminth infected populations suggests that helminth infections could protect against allergy by uncoupling asIgE from its effector mechanisms. We investigated this hypothesis in Ugandan schoolchildren coinfected with Schistosoma mansoni and hookworm. Methods. Skin prick test (SPT) sensitivity to house dust mite allergen (HDM) and current wheeze were assessed pre-anthelmintic treatment. Nonspecific (anti-IgE), helminth-specific, and HDM-allergen-specific basophil histamine release (HR), plus helminth- and HDM-specific IgE and IgG4 responses were measured pre- and post-treatment. Results. Nonspecific- and helminth-specific-HR, and associations between helminth-specific IgE and helminth-specific HR increased post-treatment. Hookworm infection appeared to modify the relationship between circulating levels of HDM-IgE and HR: a significant positive association was observed among children without detectable hookworm infection, but no association was observed among infected children. In addition, hookworm infection was associated with a significantly reduced risk of wheeze, and IgG4 to somatic adult hookworm antigen with a reduced risk of HDM-SPT sensitivity. There was no evidence for S. mansoni infection having a similar suppressive effect on HDM-HR or symptoms of allergy. Conclusions. Basophil responsiveness appears suppressed during chronic helminth infection; at least in hookworm infection, this suppression may protect against allergy. PMID:24782451

  8. Aeroallergen analyses and their clinical relevance. I. Immunochemical quantification of allergens by RAST-inhibition, Mab-ELISA, basophil histamine release, and counter current immuno electrophoresis

    DEFF Research Database (Denmark)

    Johnsen, C R; Abrahamsen, L; Stahl Skov, P;

    1991-01-01

    The aim was to compare IgE and IgG4 RAST-inhibition assay (RI), monoclonal antibody ELISA (Mab-ELISA), counter current immuno electrophoresis (CCIE) and histamine release from basophil leukocytes (HR) for allergen quantification with special reference to aeroallergen detection. As components...... and Derm. pter. (10-10(2) SQ-U/ml), and 10(2)-10(3) SQ-U/ML for dog. Because of cross-reactivity, a minor degree of interference was observed in the IgE-RI and the HR test for the highest concentration of cat and dog allergens....

  9. CALCIUM RELEASE FROM SEPARATE RECEPTOR-SPECIFIC INTRACELLULAR STORES INDUCED BY HISTAMINE AND ATP IN A HAMSTER-CELL LINE

    NARCIS (Netherlands)

    DENHERTOG, A; HOITING, B; MOLLEMAN, A; VANDENAKKER, J; DUIN, M; NELEMANS, A

    1992-01-01

    1. The specificity of intracellular Ca2+ stores to Ca2+-mobilizing agonists was studied in DDT1 MF-2 vas deferens cells of the Syrian hamster. 2. Application of histamine (100-mu-M or ATP (100-mu-m) to the DDT, MF-2 cells caused an initial increase of intracellular Ca2+ followed by a lower phase as

  10. Histamine H3 receptor activation counteracts adenosine A2A receptor-mediated enhancement of depolarization-evoked [3H]-GABA release from rat globus pallidus synaptosomes.

    Science.gov (United States)

    Morales-Figueroa, Guadalupe-Elide; Márquez-Gómez, Ricardo; González-Pantoja, Raúl; Escamilla-Sánchez, Juan; Arias-Montaño, José-Antonio

    2014-08-20

    High levels of histamine H3 receptors (H3Rs) are found in the globus pallidus (GP), a neuronal nucleus in the basal ganglia involved in the control of motor behavior. By using rat GP isolated nerve terminals (synaptosomes), we studied whether H3R activation modified the previously reported enhancing action of adenosine A2A receptor (A2AR) stimulation on depolarization-evoked [(3)H]-GABA release. At 3 and 10 nM, the A2AR agonist CGS-21680 enhanced [(3)H]-GABA release induced by high K(+) (20 mM) and the effect of 3 nM CGS-21680 was prevented by the A2AR antagonist ZM-241385 (100 nM). The presence of presynaptic H3Rs was confirmed by the specific binding of N-α-[methyl-(3)H]-histamine to membranes from GP synaptosomes (maximum binding, Bmax, 1327 ± 79 fmol/mg protein; dissociation constant, Kd, 0.74 nM), which was inhibited by the H3R ligands immepip, clobenpropit, and A-331440 (inhibition constants, Ki, 0.28, 8.53, and 316 nM, respectively). Perfusion of synaptosomes with the H3R agonist immepip (100 nM) had no effect on K(+)-evoked [(3)H]-GABA release, but inhibited the stimulatory action of A2AR activation. In turn, the effect of immepip was blocked by the H3R antagonist clobenpropit, which had no significant effect of its own on K(+)-induced [(3)H]-GABA release. These data indicate that H3R activation selectively counteracts the facilitatory action of A2AR stimulation on GABA release from striato-pallidal projections.

  11. Diagnostic value of scratch-chamber test, skin prick test, histamine release and specific IgE in birch-allergic patients with oral allergy syndrome to apple

    DEFF Research Database (Denmark)

    Osterballe, M; Scheller, R; Stahl Skov, P;

    2003-01-01

    BACKGROUND: The aim of the study was to examine the diagnostic value of skin prick test (SPT), scratch-chamber test (SCT), histamine release (HR) and specific immunoglobulin E (IgE) in birch-allergic patients with oral allergy syndrome to apple. METHODS: Ten birch-allergic patients with oral alle...... a detailed case history about symptoms of oral allergy syndrome combined with a SPT with fresh apple peel or A72 will be useful.......BACKGROUND: The aim of the study was to examine the diagnostic value of skin prick test (SPT), scratch-chamber test (SCT), histamine release (HR) and specific immunoglobulin E (IgE) in birch-allergic patients with oral allergy syndrome to apple. METHODS: Ten birch-allergic patients with oral...... allergy syndrome to apple and 10 control subjects were included. All were tested with SPT, SCT, HR and specific IgE [CAP, Pharmacia, Sweden and Magic Lite (ML), ALK-ABELLO, Denmark]. RESULTS: The SPT with apple, acetone extract of apple (A72) and commercial apple extract showed sensitivities of 0.80, 0...

  12. Limited influence of aspirin intake on mast cell activation in patients with food-dependent exercise-induced anaphylaxis: comparison using skin prick and histamine release tests.

    Science.gov (United States)

    Fukunaga, Atsushi; Shimizu, Hideki; Tanaka, Mami; Kikuzawa, Ayuko; Tsujimoto, Mariko; Sekimukai, Akiko; Yamashita, Junji; Horikawa, Tatsuya; Nishigori, Chikako

    2012-09-01

    Food-dependent exercise-induced anaphylaxis (FDEIA) is a severe systemic syndrome induced by physical exercise after ingesting causative food. Aspirin is a well-known trigger for anaphylaxis in patients with FDEIA. Possible mechanisms by which symptoms are aggravated by aspirin include enhanced antigen absorption and mast cell activation. The aim of this study was to determine whether aspirin intake has an influence on mast cell/basophil activation in patients with FDEIA. Provocation tests revealed that adding aspirin to the causative food challenge in 7 of 9 (77.8%) patients with FDEIA provoked symptoms. In most cases, pretreatment with aspirin did not enhance skin tests (71.4%) or histamine release tests (88.9%) with food allergen challenges. The study confirms that histamine release and skin prick tests can be adjunctive tools for diagnosing FDEIA. In addition, our results suggest that exacerbation of FDEIA symptoms by aspirin is not mediated by direct effects of aspirin on mast cell/basophil activation.

  13. Histamine immunocytochemistry

    DEFF Research Database (Denmark)

    Jacobi, H H; Johansson, O; Liang, Y

    2000-01-01

    We report that basophils in peripheral blood can be stained using histamine immunocytochemistry. The staining is based on the fixation of leucocytes with 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (CDI) and the subsequent incubation of these cells with antisera raised against histamine...... conjugated to different carrier proteins using CDI. The staining appears to be specific for basophils and stained cells can be examined using both fluorescence microscopy and flow cytometry. In addition, histamine immunocytochemistry can be combined with conventional immunocytochemistry by incubating...... leucocytes with antibodies to cell surface antigens prior to or following fixation of the cells with CDI. Thus, histamine immunocytochemistry may be a valuable tool in future studies of human basophils....

  14. In Vitro Inhibition of Histamine Release Behavior of Cetirizine Intercalated into Zn/Al- and Mg/Al-Layered Double Hydroxides

    Directory of Open Access Journals (Sweden)

    Muhammad Nazrul Hakim

    2012-05-01

    Full Text Available The intercalation of cetirizine into two types of layered double hydroxides, Zn/Al and Mg/Al, has been investigated by the ion exchange method to form CTZAN and CTMAN nanocomposites, respectively. The basal spacing of the nanocomposites were expanded to 31.9 Å for CTZAN and 31.2 Å for CTMAN, suggesting that cetirizine anion was intercalated into Layered double hydroxides (LDHs and arranged in a tilted bilayer fashion. A Fourier transform infrared spectroscopy (FTIR study supported the formation of both the nanocomposites, and the intercalated cetirizine is thermally more stable than its counterpart in free state. The loading of cetirizine in the nanocomposite was estimated to be about 57.2% for CTZAN and 60.7% CTMAN. The cetirizine release from the nanocomposites show sustained release manner and the release rate of cetirizine from CTZAN and CTMAN nanocomposites at pH 7.4 is remarkably lower than that at pH 4.8, presumably due to the different release mechanism. The inhibition of histamine release from RBL2H3 cells by the free cetirizine is higher than the intercalated cetirizine both in CTZAN and CTMAN nanocomposites. The viability in human Chang liver cells at 1000 μg/mL for CTZAN and CTMAN nanocomposites are 74.5 and 91.9%, respectively.

  15. Evaluation of the correlation and reproducibility between histamine, IL-4, and IL-13 release from human basophils.

    OpenAIRE

    Nahid Eskandari; Reza Bastan; Maryam Ahmadi; Peachell, Peter T

    2014-01-01

    Human basophils play a key role in allergic diseases such as asthma and in a variety of immunological disorders. The generation of IL-4 and IL-13 can be induced from basophil by IgE-mediated and non-IgE-mediated mechanisms. Time and stimulus-dependent differences in the regulation of these cytokines could have relevance to their biological effects. The aim of the present study was activation of basophils in order to evaluate the extent of histamine, IL-4, and IL-13 generations. Basophil-enric...

  16. Histamine H3 receptor activation prevents dopamine D1 receptor-mediated inhibition of dopamine release in the rat striatum: a microdialysis study.

    Science.gov (United States)

    Alfaro-Rodriguez, Alfonso; Alonso-Spilsbury, María; Arch-Tirado, Emilio; Gonzalez-Pina, Rigoberto; Arias-Montaño, José-Antonio; Bueno-Nava, Antonio

    2013-09-27

    Histamine H3 receptors (H3Rs) co-localize with dopamine (DA) D1 receptors (D1Rs) on striatal medium spiny neurons and functionally antagonize D1R-mediated responses. The intra-striatal administration of D1R agonists reduces DA release whereas D1R antagonists have the opposite effect. In this work, a microdialysis method was used to study the effect of co-activating D1 and H3 receptors on the release of DA from the rat dorsal striatum. Infusion of the D1R agonist SKF-38393 (0.5 and 1 μM) significantly reduced DA release (26-58%), and this effect was prevented by co-administration of the H3R agonist immepip (10 μM). In turn, the effect of immepip was blocked by the H3R antagonist thioperamide (10 μM). Our results indicate that co-stimulation of post-synaptic D1 and H3 receptors may indirectly regulate basal DA release in the rat striatum and provide in vivo evidence for a functional interaction between D1 and H3 receptors in the basal ganglia.

  17. Histamine receptors in isolated bovine oviductal arteries.

    Science.gov (United States)

    Martínez, A C; Novella, S; Raposo, R; Recio, P; Labadía, A; Costa, G; Garcia-Sacristán, A; Benedito, S

    1997-05-20

    dilatation was practically abolished by mepyramine and also by indomethacin. The L-arginine analogue, N(omega)-nitro-L-arginine methyl ester (L-NAME) inhibited the effect of histamine and basal production of nitric oxide. L-Arginine, which on its own induced significant endothelium-dependent vasodilatation, reversed the effect of L-NAME on histamine relaxation. Indomethacin only caused a slight modification of the sensitivity of the vessels to histamine, suggesting that prostacyclin or other cyclo-oxygenase products did not make a significant contribution to the model. The absence of the endothelium did not modify the contractile effect of histamine. The results suggest that the relaxant response of isolated oviductal arteries to histamine is dependent on the functional integrity of the endothelium and is mainly mediated by histamine H1 receptors. These receptors may mask a minority presence of histamine H3 contractile receptors located on smooth muscle. The main relaxing factor released from the endothelium by mediation of histamine is nitric oxide, which may also exert an effect on vascular tone.

  18. Gender-Related Effects of Sex Steroids on Histamine Release and FcεRI Expression in Rat Peritoneal Mast Cells

    Directory of Open Access Journals (Sweden)

    Samira Muñoz-Cruz

    2015-01-01

    Full Text Available Mast cells (MCs are versatile effector and regulatory cells in various physiologic, immunologic, and pathologic processes. In addition to the well-characterized IgE/FcεRI-mediated degranulation, a variety of biological substances can induce MCs activation and release of their granule content. Sex steroids, mainly estradiol and progesterone, have been demonstrated to elicit MCs activation. Most published studies have been conducted on MCs lines or freshly isolated peritoneal and bone marrow-derived MC without addressing gender impact on MC response. Our goal was to investigate if the effect of estradiol, progesterone, testosterone, and dihydrotestosterone (DHT on MCs may differ depending on whether female or male rats are used as MCs donors. Our results demonstrated that effect of sex steroids on MCs histamine release is dose- and gender-dependent and can be direct, synergistic, or inhibitory depending on whether hormones are used alone or to pretreat MCs followed by substance P-stimulation or upon IgE-mediated stimulation. In contrast, sex steroids did not have effect on the MC expression of the IgE high affinity receptor, FcεRI, no matter female or male rats were used. In conclusion, MCs degranulation is modulated by sex hormones in a gender-selective fashion, with MC from females being more susceptible than MC from males to the effects of sex steroids.

  19. Histamine in the regulation of wakefulness.

    Science.gov (United States)

    Thakkar, Mahesh M

    2011-02-01

    The histaminergic system is exclusively localized within the posterior hypothalamus with projection to almost all the major regions of the central nervous system. Strong and consistent evidence exist to suggest that histamine, acting via H₁ and/or H₃ receptor has a pivotal role in the regulation of sleep-wakefulness. Administration of histamine or H₁ receptor agonists induces wakefulness, whereas administration of H₁ receptor antagonists promotes sleep. The H₃ receptor functions as an auto-receptor and regulates the synthesis and release of histamine. Activation of H₃ receptor reduces histamine release and promotes sleep. Conversely, blockade of H₃ receptor promotes wakefulness. Histamine release in the hypothalamus and other target regions is highest during wakefulness. The histaminergic neurons display maximal activity during the state of high vigilance, and cease their activity during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. The cerebrospinal levels of histamine are reduced in diseased states where hypersomnolence is a major symptom. The histamine deficient L-histidine decarboxylase knockout (HDC KO) mice display sleep fragmentation and increased REM sleep during the light period along with profound wakefulness deficit at dark onset, and in novel environment. Similar results have been obtained when histamine neurons are lesioned. These studies strongly implicate the histaminergic neurons of the TMN to play a critical role in the maintenance of high vigilance state during wakefulness.

  20. Rabbit IgG directed to a synthetic C-terminal peptide of the major grass pollen allergen Lol p I inhibits human basophil histamine release induced by natural Lol p I.

    Science.gov (United States)

    van Ree, R; Aalberse, R C

    1995-03-01

    The potential role of allergen-specific IgG antibodies as 'blocking' antibodies in allergen-induced human basophil histamine release was investigated. This was studied in a model with the major grass pollen allergen Lol p I and polyclonal rabbit antisera directed against this allergen and against a synthetic peptide of its C terminus. When allergen and antibodies were allowed to preincubate, Lol p I induced histamine release was inhibited up to 85% by the antiserum against Lol p I. By omitting preincubation, and thereby more closely mimicking an in vivo situation, up to 55% inhibition was realized. This indicates that allergen-specific IgG can act as 'blocking' antibody without preincubation. Immunization of rabbits with a synthetic C-terminal peptide of Lol p I resulted in antibodies reactive with natural Lol p I. Despite their 100-fold lower avidity for Lol p I (as compared with antinatural Lol p I), these antibodies had the capacity to inhibit Lol p I induced histamine release for > 90% (up to 50% without preincubation). This indicates that it is possible to block histamine release induced by a major allergen with low-avidity IgG antibodies directed against a minor proportion of the allergen (25 amino acids). IgE antibodies from the donors studied were unreactive with this synthetic peptide, indicating that for blocking activity identical epitope specificity of IgE and IgG is not essential. This opens interesting perspectives for application of synthetic peptides in immunotherapy, distinct from their effects on T cell reactivity.

  1. Accumulation of radioactive cesium released from Fukushima Daiichi Nuclear Power Plant in terrestrial cyanobacteria Nostoc commune.

    Science.gov (United States)

    Sasaki, Hideaki; Shirato, Susumu; Tahara, Tomoya; Sato, Kenji; Takenaka, Hiroyuki

    2013-01-01

    The Fukushima Daiichi Nuclear Power Plant accident released large amounts of radioactive substances into the environment and contaminated the soil of Tohoku and Kanto districts in Japan. Removal of radioactive material from the environment is an urgent problem, and soil purification using plants is being considered. In this study, we investigated the ability of 12 seed plant species and a cyanobacterium to accumulate radioactive material. The plants did not accumulate radioactive material at high levels, but high accumulation was observed in the terrestrial cyanobacterium Nostoc commune. In Nihonmatsu City, Fukushima Prefecture, N. commune accumulated 415,000 Bq/kg dry weight (134)Cs and 607,000 Bq kg(-1) dry weight (137)Cs. The concentration of cesium in N. commune tended to be high in areas where soil radioactivity was high. A cultivation experiment confirmed that N. commune absorbed radioactive cesium from polluted soil. These data demonstrated that radiological absorption using N. commune might be suitable for decontaminating polluted soil.

  2. Ciproxifan, a histamine H3 receptor antagonist and inverse agonist, presynaptically inhibits glutamate release in rat hippocampus.

    Science.gov (United States)

    Lu, Cheng-Wei; Lin, Tzu-Yu; Chang, Chia-Ying; Huang, Shu-Kuei; Wang, Su-Jane

    2017-03-15

    Ciproxifan is an H3 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(2+)-dependent glutamate release and cytosolic Ca(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 Cav2.2 (N-type) and Cav2.1 (P/Q-type) channel blocker ω-conotoxin MVIIC, but was not affected by the intracellular Ca(2+)-release inhibitors dantrolene and CGP37157. Furthermore, the phospholipase A2 (PLA2) inhibitor OBAA, prostaglandin E2 (PGE2), PGE2 subtype 2 (EP2) 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 H3 receptors present on hippocampal nerve terminals, reduces voltage-dependent Ca(2+) entry by diminishing PLA2/PGE2/EP2 receptor pathway, which subsequently suppresses the ERK/synapsin I cascade to decrease the evoked glutamate release.

  3. Time- and dose-dependent responses of brain histamine to intracerebroventricular and intraperitoneal administrations of growth hormone-releasing factor (GRF1-44).

    Science.gov (United States)

    Cacabelos, R; Yamatodani, A; Fukui, H; Niigawa, H; Miyake, A; Watanabe, T; Nishimura, T; Wada, H

    1987-04-01

    Changes in the level of histamine (HA) in rat brain induced by intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) administrations of growth hormone-releasing factor (GRF1-44) were studied. HA was determined by high-performance liquid chromatography (HPLC) in the anterior hypothalamic region, posterior hypothalamic region, median eminence, adenohypophysis, neurohypophysis, hippocampus and prefrontal cortex. GRF1-44 (1-10 micrograms, i.c.v.) induced significant time- and dose-dependent increases in the concentration of HA in the hypothalamo-hypophyseal system and time-dependent decrease of HA in the hippocampus. In contrast, after i.p. administration of GRF1-44 (10 micrograms) the level of HA in the hypothalamus tended to decrease but the total amount of H-1 receptors in the hypothalamo-hypophyseal system did not change. Circadian variations in the GRF-induced HA and growth hormone responses were also observed, responses being lower in the evening than in the morning. It is concluded that GRF interacts with HA at the central level to optimize the function of the somatotropinergic system.

  4. Cold urticaria patients exhibit normal skin levels of functional mast cells and histamine after tolerance induction

    DEFF Research Database (Denmark)

    Kring Tannert, Line; Stahl Skov, Per; Bjerremann Jensen, Louise

    2012-01-01

    to cold can be beneficial. The aim was to investigate whether desensitization can lower temperature thresholds and reduce release of histamine in the skin. Cold urticaria patients were subjected to desensitization and assessed for skin responses to cold stimulation and codeine before and after. Histamine...... prevented histamine release after skin exposure to cold. Surprisingly, skin histamine levels and release after codeine injection were found to be normal in desensitized patients....

  5. Histamine and histamine type-2 receptor antagonists in psoriasis. Mechanisms and speculations

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen

    1991-01-01

    The findings that the immunosuppressant cyclosporine A (CsA) improves psoriasis raise the possibility that cellular immune processes may play a major role in the pathogenesis of this disease. It is broadly agreed that histamine released by mast cells is one of the molecules involved...... in the pathogenesis. This is supported by the findings that CsA and methotrexate (Mxt) reduce formation and release of histamine. However, the well known side-effects of CsA and Mxt may argue potential use of other agents acting on formation and action of histamine. Such agents may be the histamine-2 receptor...... antagonists, previously reported to have a clinical effect on psoriasis. But randomised short-term studies have disclosed that these drugs have no beneficial or even an aggravating effect on the disease. This article reports on recent findings of improvement in psoriasis using high doses of the histamine-2...

  6. Histamine in regulation of bone remodeling processes

    Directory of Open Access Journals (Sweden)

    Marek Wiercigroch

    2013-08-01

    Full Text Available Bone remodeling is under autocrine, paracrine, endocrine and central nervous system control. One of the potential endogenous factors affecting bone remodeling is histamine, an endogenous amine which acts as a mediator of allergic reactions and neuromediator, and induces production of gastric acid. Histamine H1 receptor antagonists are widely used in the treatment of allergic conditions, H2 receptor antagonists in peptic ulcer disease, and betahistine (an H3 receptor antagonist and H1 receptor agonist is used in the treatment of Ménière’s disease.Excess histamine release in mastocytosis and allergic diseases may lead to development of osteoporosis. Clinical and population-based studies on the effects of histamine receptor antagonists on the skeletal system have not delivered unequivocal results.Expression of mRNA of histamine receptors has been discovered in bone cells (osteoblasts and osteoclasts. Histamine synthesis has been demonstrated in osteoclast precursors. Histamine increases bone resorption both by direct effects on osteoclast precursors and osteoclasts, and indirectly, by increasing the expression of RANKL in osteoblasts. In in vivo studies, H1 and H2 receptor antagonists exerted protective effects on the bone tissue, although not in all experimental models. In the present article, in vitro and in vivo studies conducted so far, concerning the effects of histamine and drugs modifying its activity on the skeletal system, have been reviewed.

  7. Histamine regulates the inflammatory response of the tunicate Styela plicata.

    Science.gov (United States)

    García-García, Erick; Gómez-González, Nuria E; Meseguer, José; García-Ayala, Alfonsa; Mulero, Victoriano

    2014-10-01

    Histamine is stored inside hemocytes of the tunicate Styela plicata (Chordata, Tunicata, Ascidiacea), but no evidence on its role in the regulation of the immune response of this species has been reported. We examined whether histamine participated in the regulation of inflammation and host defense in S. plicata. The presence of histamine inside S. plicata hemocytes was confirmed by flow cytometry, and histamine release was detected by ELISA, after in vitro hemocyte stimulation with different PAMPs. In vitro hemocyte treatment with histamine, or specific histamine-receptor agonists, reduced their phagocytic ability. Injection of histamine into the tunic recruited hemocytes to the site of injection. Systemic injection of histamine, or the histamine-releasing agent compound 48/80, decreased the phagocytic ability of hemocytes. Histamine promoted the constriction of tunic hemolymph vessels in vivo, having a direct effect on vasoconstriction in tunic explants. These results provide for the first time clear evidence for the involvement of histamine in the regulation of inflammation and host defense in tunicates.

  8. Neuronal histamine and expression of corticotropin-releasing hormone, vasopressin and oxytocin in the hypothalamus: relative importance of H1 and H2 receptors.

    Science.gov (United States)

    Kjaer, A; Larsen, P J; Knigge, U; Jørgensen, H; Warberg, J

    1998-08-01

    Centrally administered histamine (HA) stimulates the secretion of the pro-opiomelanocortin-derived peptides ACTH and beta-endorphin as well as prolactin. The effect of HA on secretion of these adenohypophysial hormones is indirect and may involve activation of hypothalamic neurons containing corticotropin-releasing hormone (CRH), arginine-vasopressin (AVP) or oxytocin (OT). We studied the effect of activating central HA receptors by central infusion of HA, HA agonists or antagonists on expression of CRH, AVP and OT mRNA in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. Intracerebroventricular infusion of HA (270 nmol), the H1-receptor agonist 2-thiazolylethylamine or the H2-receptor agonist 4-methylhistamine increased the level of CRH mRNA in the PVN, and OT mRNA in the SON. In contrast, none of these compounds had any effect on expression of AVP mRNA in the PVN or SON. Administration of the H1-receptor antagonist mepyramine or the H2-receptor antagonist cimetidine had no effect on basal expression of CRH, AVP or OT mRNA in the PVN and/or SON except for a slight inhibitory effect of cimetidine on CRH mRNA expression in the PVN. Pretreatment with mepyramine or cimetidine before HA administration inhibited the HA-induced increase in OT mRNA levels but had no effect on the HA-induced increase in CRH mRNA levels in the PVN. We conclude that HA stimulates hypothalamic CRH and OT neurons by increasing mRNA levels, and this effect seems to be mediated via activation of both HA H1 and H2 receptors.

  9. Aeroallergen analyses and their clinical relevance. I. Immunochemical quantification of allergens by RAST-inhibition, Mab-ELISA, basophil histamine release, and counter current immuno electrophoresis.

    Science.gov (United States)

    Johnsen, C R; Abrahamsen, L; Stahl Skov, P; Johansen, N; Poulsen, L K

    1991-10-01

    The aim was to compare IgE and IgG4 RAST-inhibition assay (RI), monoclonal antibody ELISA (Mab-ELISA), counter current immuno electrophoresis (CCIE) and histamine release from basophil leukocytes (HR) for allergen quantification with special reference to aeroallergen detection. As components of indoor aeroallergens, cat, dog, and Derm. pter. allergen extracts were selected for the experiments. To evaluate unspecific interference, these allergens were compared mutually and with Cladosporium herbarum. Allergen extracts in varying dilutions were mixed with crushed glass fibre filter materials, eluted, recovered by centrifugation, and allergen concentration quantified by the assays. Equal sensitivity was found for both IgE- and IgG4-RI assaying cat allergen (in the range 5-50 SQ-U/ml) and dog allergen (in the range 10(2)-10(3) SQ-U/ml). The IgG4-RI assaying Derm. pter. was more sensitive (50 SQ-U/ml) than IgE-RI (2*10(3) SQ-U/ml). The ranges of allergen detection limits for the Mab-ELISA were equal for cat and Derm. pter. (10-10(2) SQ-U/ml). The range of allergen detection limits for CCIE, assaying dog were 10(4)-10(5) SQ-U/ml. The ranges of allergen detection limits for HR were equal for cat and Derm. pter. (10-10(2) SQ-U/ml), and 10(2)-10(3) SQ-U/ML for dog. Because of cross-reactivity, a minor degree of interference was observed in the IgE-RI and the HR test for the highest concentration of cat and dog allergens.

  10. Inhibition of histamine release by local and intracerebroventricular infusion of galanin in hypothalamus, hippocampus and prefrontal cortex of awake rat: A microdialysis study.

    Science.gov (United States)

    Yoshitake, Shimako; Ijiri, Soichiro; Kehr, Jan; Yoshitake, Takashi

    2013-02-08

    The neuropeptide galanin is co-localized with histamine in subpopulations of neurons in the tuberomammillary nucleus suggesting its involvement in modulating histaminergic neurotransmission. The purpose of the present study was to investigate, by use of microdialysis, the effects of local intraparenchymal (combined infusion and microdialysis probe), and intracerebroventricular (i.c.v.) infusions of galanin on extracellular levels of histamine in its major projecting areas, ventromedial hypothalamic nucleus ventrolateral part (VMHVL), CA3 area of ventral hippocampus (vHipp) and medial prefrontal cortex (mPFC) in separate groups (n=5 rats/each) of freely moving rats. Galanin (0.5nmol and 1.5nmol) dose-dependently decreased the basal histamine levels in the VMHVL to 77.1% (i.c.v.) at 40min and to 82.1% (intra-VMHVL infusion) already at 20min, of the control group (32.6±3.5fmol/10μl), whereas only 1.5nmol i.c.v. galanin and not the local infusions deceased the histamine levels in the vHipp (8.4±0.6fmol/10μl) to 82.8% and in mPFC (9.8±0.9fmol/10μl) to 87.5%. It is concluded that central administration of galanin decreased the basal extracellular histamine levels in major histamine projecting areas, however, these effects were less prominent than those observed for 5-HT (Kehr et al., 2002 [12]) and ACh (Yoshitake et al., 2011 [38]) in the ventral hippocampus following i.c.v. and/or local galanin infusions.

  11. Modelling for Forest Fire Evolution Based on the Energy Accumulation and Release

    Directory of Open Access Journals (Sweden)

    Fan Yang

    2015-09-01

    Full Text Available Forest fire evolution plays an important role in the decision-making of controlling the forest fire. This paper aims to simulate the dynamics of the forest fire spread using a cellular automaton approach. Having analyzed the characteristics and evolution of forest fires, a simulation model for the forest fire evolution based on the energy accumulation and release is proposed. And, taking Australia's catastrophic forest fire in 2009 as an example, the fire’s evolution closely to the reality is simulated. The results of the experiments are shown that if forest energy is released in a small scale before or during the fire, the fire would be better controlled even if it does not occur. Improving the efficiency of the fire extinguishing procedures and reducing the speed of the fire spread are also effective for controlling the forest fire.

  12. Cellulose conjugated FITC-labelled mesoporous silica nanoparticles: intracellular accumulation and stimuli responsive doxorubicin release

    Science.gov (United States)

    Hakeem, Abdul; Zahid, Fouzia; Duan, Ruixue; Asif, Muhammad; Zhang, Tianchi; Zhang, Zhenyu; Cheng, Yong; Lou, Xiaoding; Xia, Fan

    2016-02-01

    Herein, we design novel cellulose conjugated mesoporous silica nanoparticle (CLS-MSP) based nanotherapeutics for stimuli responsive intracellular doxorubicin (DOX) delivery. DOX molecules are entrapped in pores of the fabricated mesoporous silica nanoparticles (MSPs) while cellulose is used as an encapsulating material through esterification on the outlet of the pores of the MSPs to avoid premature DOX release under physiological conditions. In in vitro studies, stimuli responsive DOX release is successfully achieved from DOX loaded cellulose conjugated mesoporous silica nanoparticles (DOX/CLS-MSPs) by pH and cellulase triggers. Intracellular accumulation of DOX/CLS-MSPs in human liver cancer cells (HepG2 cells) is investigated through confocal microscope magnification. Cell viability of HepG2 cells is determined as the percentage of the cells incubated with DOX/CLS-MSPs compared with that of non-incubated cells through an MTT assay.Herein, we design novel cellulose conjugated mesoporous silica nanoparticle (CLS-MSP) based nanotherapeutics for stimuli responsive intracellular doxorubicin (DOX) delivery. DOX molecules are entrapped in pores of the fabricated mesoporous silica nanoparticles (MSPs) while cellulose is used as an encapsulating material through esterification on the outlet of the pores of the MSPs to avoid premature DOX release under physiological conditions. In in vitro studies, stimuli responsive DOX release is successfully achieved from DOX loaded cellulose conjugated mesoporous silica nanoparticles (DOX/CLS-MSPs) by pH and cellulase triggers. Intracellular accumulation of DOX/CLS-MSPs in human liver cancer cells (HepG2 cells) is investigated through confocal microscope magnification. Cell viability of HepG2 cells is determined as the percentage of the cells incubated with DOX/CLS-MSPs compared with that of non-incubated cells through an MTT assay. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr08753h

  13. [Histamine intolerance--possible dermatologic sequences].

    Science.gov (United States)

    Lugović-Mihić, Liborija; Seserko, Ana; Duvancić, Tomislav; Situm, Mirna; Mihić, Josip

    2012-12-01

    Although histamine intolerance (HIT) is not very frequently encountered, it can have serious consequences. Food intolerance is a non allergic hypersensitivity to food that does not include the immune system even though the symptoms are similar to those of IgE-mediated allergic reactions. HIT apparently develops as a result of an impaired diamine oxidase (DAO) activity due to gastrointestinal disease or through DAO inhibition, as well as through a genetic predisposition which was proven in a number of patients. The intake of histamine-rich foods as well as alcohol or drugs which cause either the release of histamine or the blocking of DAO can lead to various disorders in many organs (gastrointestinal system, skin, lungs, cardiovascular system and brain), depending on the expression of histamine receptors. Dermatologic sequels can be rashes, itch, urticaria, angioedema, dermatitis, eczema and even acne, rosacea, psoriasis, and other. Recognizing the symptoms due to HIT is especially important in treating such patients. The significance of HIT in patients with atopic dermatitis in whom the benefit of a low histamine diet has been proven is becoming increasingly understood recently. Because of the possibility of symptoms affecting numerous organs, a detailed history of symptoms following the intake of histamine-rich foods or drugs that interfere with histamine metabolism is essential for making the diagnosis of HIT. Considering that such symptoms can be the result of multiple factors, the existence of HIT is usually underestimated, but considerable expectations are being made from future studies.

  14. Histamine and Skin Barrier: Are Histamine Antagonists Useful for the Prevention or Treatment of Atopic Dermatitis?

    Science.gov (United States)

    De Benedetto, Anna; Yoshida, Takeshi; Fridy, Sade; Park, Joo-Eun S; Kuo, I-Hsin; Beck, Lisa A

    2015-04-21

    Atopic Dermatitis (AD), the most common chronic inflammatory skin disease, is characterized by an overactive immune response to a host of environmental allergens and dry, itchy skin. Over the past decade important discoveries have demonstrated that AD develops in part from genetic and/or acquired defects in the skin barrier. Histamine is an aminergic neurotransmitter involved in physiologic and pathologic processes such as pruritus, inflammation, and vascular leak. Enhanced histamine release has been observed in the skin of patients with AD and antihistamines are often prescribed for their sedating and anti-itch properties. Recent evidence suggests that histamine also inhibits the terminal differentiation of keratinocytes and impairs the skin barrier, raising the question whether histamine might play a role in AD barrier impairment. This, coupled with the notion that histamine's effects mediated through the recently identified histamine receptor H4R, may be important in allergic inflammation, has renewed interest in this mediator in allergic diseases. In this paper we summarize the current knowledge on histamine and histamine receptor antagonists in AD and skin barrier function.

  15. TLR-induced activation of neutrophils promotes histamine production via a PI3 kinase dependent mechanism.

    Science.gov (United States)

    Smuda, Craig; Wechsler, Joshua B; Bryce, Paul J

    2011-12-30

    Histamine is a bioactive amine that exerts immunomodulatory functions, including many allergic symptoms. It is preformed and stored in mast cells and basophils but recent evidence suggests that other cell types produce histamine in an inducible fashion. During infection, it has been suggested that neutrophils may produce histamine. We also observed that histamine is released in a neutrophil-mediated LPS-induced model of acute lung injury. Therefore, we sought to examine whether innate signals promote histamine production by neutrophils. Bone marrow-derived neutrophils stimulated with a range of TLR agonists secreted histamine in response to LPS or R837, suggesting TLR4 or TLR7 are important. LPS-driven histamine was enhanced by coculture with GM-CSF and led to a transient release of histamine that peaked at 8h post stimulation. This was dependent upon de novo synthesis of histamine, since cells derived from histidine decarboxylase (HDC) deficient mice were unable to produce histamine but did generate reactive oxygen species upon stimulation. Using pharmacological inhibitors, we show that histamine production requires PI3 kinase, which has been shown to regulate other neutrophil functions, including activation and selective granule release. However, unlike mast cells, HDC deficiency did not alter the granule structure of neutrophils, suggesting that histamine does not participate in granule integrity in these cells. Consequently, our findings establish that neutrophils generate histamine in response to a select panel of innate immune triggers and that this might contribute to acute lung injury responses.

  16. Co-localization of histamine and norepinephrine in sympathetic ganglia and exocytosis of endogenous histamine from cardiac sympathetic nerve endings of macaca mulatto monkey

    Institute of Scientific and Technical Information of China (English)

    Ming-kaiLI; Xiao-xingLUO; Liang-weiCHEN; ZhongCHEN; JiaMENG; JingHU; Yu-meiWU; Jing-ruMENG; ZhengHOU; XueMA

    2005-01-01

    AIM To provide the evidence about localization, biosynthesis, metabolism and release of histamine from the cardiac sympathetic nerve terminals, and endogenous sympathetic histamine could inhibit itsel frelease from the nerve terminal through the presynaptic histamine H3 receptor. METHODS Using double-labeled immunohistochemistry to observe the co-localization of histamine and NE in the superior cer-vical ganglia (SCG) of macaca mulatto monkey; Different-speed centrifugation to obtain the cardiac sympathetic nerve terminal model (the cardiac synaptosomes), spectrofluorometer and ELISA techniques to detect the release of histamine from the cardiacsynaptosomes. RESULTS ( 1 ) The coexistence of histamine and norepinephrine immunoreactivities was identified in the same neuron within SCG of macaca mulatto monkey. (2) Depolarization of macaca mulatto monkey cardiac synaptosomes with 50 mmol/L potassium caused the release of endogenous histamine,

  17. 嗜碱粒细胞组胺释放试验检测抗高亲和力IgE抗体及其受体%Significance of basophil histamine release assays in chronic urticaria

    Institute of Scientific and Technical Information of China (English)

    刘荣卿; 孙仁山

    2001-01-01

    Objective To Investigate the pathogenesis of chronic idiopathic urticaria.Methods Basophil histamine release assay was utilized.Result 15 of 32 cases(46.9%)had increased serum histamine releasing activities. This implied that anti-FcεR1 and anti-IgE autoantibodies existed in the sera of some patients with chronic idiopathic urticaria.Conclusion It suggested that autoimmunity might take part in the occurrence of some patients with chronic idiopathic urticaria.%目的 探讨慢性荨麻疹的发生机制。方法 用嗜碱粒细胞组胺释放试验,检测慢性特发性荨麻疹患者的血清组胺释放活性。结果 32例中,有15例(46.9%)患者血清组胺释放活性增高,提示抗FcεR1或抗IgE自身抗体的存在。结论 部分慢性荨麻疹的发生与自身免疫机制有关。

  18. 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 proliferation and angiogenesis. Specific histamine receptors have been identified on the surface of bone marrow cells, immune competent cells, endothelial cells, fibroblasts, and also on malignant cells. This has prompted research in regulation by specific histamine receptor agonists and antagonists. Results...... from such studies are currently accumulating and suggest that the histamine-2 receptor antagonists have potential beneficial effects in the treatment of certain malignant, autoimmune and skin diseases, either alone or in combination with other drugs. The beneficial effect of histamine-2 receptor...

  19. Histamine and histamine intolerance%组胺及组胺不耐受

    Institute of Scientific and Technical Information of China (English)

    江凤; 王华

    2012-01-01

    组胺是一种具有多种生物学活性的化学介质,在体内主要由二胺氧化酶和组胺-N-甲基转移酶降解.各种原因导致的组胺代谢酶水平或活性降低及外源性组胺增加,均可引起体内组胺蓄积并产生组胺不耐受.组胺不耐受表现为一系列过敏反应样症状,涉及多个系统,食物和药物可诱发和加重这些症状.根据典型临床表现、摄入无组胺饮食或使用抗组胺药物后症状可改善、组胺双盲对照激发试验阳性、血清组胺浓度升高和二胺氧化酶活性降低可确诊组胺不耐受.%Histamine is a chemical mediator possessing multiple biological activities,which is degraded by diamine oxidase and histamine-N-methyltransferase in vivo.Either decreased levels or impaired activities of histamine-metabolizing enzymes and increased concentration of exogenous histamine can induce histamine accumulation and intolerance.Clinically,histamine intolerance mimics allergy with the involvement of multiple systems,which can be induced and aggravated by foods and drugs.Final diagnosis of histamine intolerance could be confirmed according to typical symptoms,improvement of symptoms by histamine-free diet and antihistamines,positive results yielded by histamine in double-blind,placebo-controlled provocation test,elevated serum histamine concentration and diminished diamine oxidase activity.

  20. Histamine and histamine type-2 receptor antagonists in psoriasis. Mechanisms and speculations

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen

    1991-01-01

    The findings that the immunosuppressant cyclosporine A (CsA) improves psoriasis raise the possibility that cellular immune processes may play a major role in the pathogenesis of this disease. It is broadly agreed that histamine released by mast cells is one of the molecules involved in the pathog......The findings that the immunosuppressant cyclosporine A (CsA) improves psoriasis raise the possibility that cellular immune processes may play a major role in the pathogenesis of this disease. It is broadly agreed that histamine released by mast cells is one of the molecules involved...... in the pathogenesis. This is supported by the findings that CsA and methotrexate (Mxt) reduce formation and release of histamine. However, the well known side-effects of CsA and Mxt may argue potential use of other agents acting on formation and action of histamine. Such agents may be the histamine-2 receptor...... antagonists, previously reported to have a clinical effect on psoriasis. But randomised short-term studies have disclosed that these drugs have no beneficial or even an aggravating effect on the disease. This article reports on recent findings of improvement in psoriasis using high doses of the histamine-2...

  1. Helicobacter pylori neutrophil-activating protein induces release of histamine and interleukin-6 through G protein-mediated MAPKs and PI3K/Akt pathways in HMC-1 cells.

    Science.gov (United States)

    Tsai, Chung-Che; Kuo, Ting-Yu; Hong, Zhi-Wei; Yeh, Ying-Chieh; Shih, Kuo-Shun; Du, Shin-Yi; Fu, Hua-Wen

    2015-01-01

    Helicobacter pylori neutrophil-activating protein (HP-NAP) activates several innate leukocytes including neutrophils, monocytes, and mast cells. It has been reported that HP-NAP induces degranulation and interleukin-6 (IL-6) secretion of rat peritoneal mast cells. However, the molecular mechanism is not very clear. Here, we show that HP-NAP activates human mast cell line-1 (HMC-1) cells to secrete histamine and IL-6. The secretion depends on pertussis toxin (PTX)-sensitive heterotrimeric G proteins but not on Toll-like receptor 2. Moreover, HP-NAP induces PTX-sensitive G protein-mediated activation of extracellular signal-regulated kinase 1/2 (ERK1/2), p38-mitogen-activated protein kinase (p38 MAPK), and Akt in HMC-1 cells. Inhibition of ERK1/2, p38 MAPK, or phosphatidylinositol 3-kinase (PI3K) suppresses HP-NAP-induced release of histamine and IL-6 from HMC-1 cells. Thus, the activation of HMC-1 cells by HP-NAP is through Gi-linked G protein-coupled receptor-mediated MAPKs and PI3K/Akt pathways.

  2. The seismicity research in the sub-regions of Chinese mainland using strain accumulating and releasing model

    Institute of Scientific and Technical Information of China (English)

    马宏生; 刘杰; 张国民; 李丽

    2002-01-01

    The sub-regions are divided for the seismicity of the Chinese mainland based on the hypothesis of the active crustal blocks and the division of the active boundaries. On this result, the seismicity of each active crustal blocks are studied by calculating the accumulated and released strain of the earthquakes based on strain accumulating and releasing model, and the different seismicity stages of the sub-regions are discussed basically. Finally we have discussed the premise of the model application and the potential problems of the model results.

  3. Possible role of histamine in pathogenesis of autoimmune diseases: implications for immunotherapy with histamine-2 receptor antagonists

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Hammer, J H

    1992-01-01

    disease activity. Histamine is suggested to be involved in the pathogenesis of psoriasis and the histamine-2 receptor antagonist ranitidine has been shown to be of value to reduce severe psoriatic disease. The finding that CsA and Mx efficiently reduce histamine formation and release raises...... the possibility, that histamine is one of the molecules involved in pathogenesis of autoimmune diseases. T cell mediated regulation and suppression of autoreactive T cells seem to be ineffective in controlling the enhanced immune reaction in patients where the discrimination between self and non-self is changed....... A consequence of this may be induction of interferon-gamma (IFN-g) production and release by cytotoxic T cells, subsequently leading to expression of MHC II molecules on non-immune tissues. As immunotherapy may be of value in some autoimmune diseases the use of histamine-2 receptor antagonists should...

  4. Histamine H3 receptor in primary mouse microglia inhibits chemotaxis, phagocytosis, and cytokine secretion.

    Science.gov (United States)

    Iida, Tomomitsu; Yoshikawa, Takeo; Matsuzawa, Takuro; Naganuma, Fumito; Nakamura, Tadaho; Miura, Yamato; Mohsen, Attayeb S; Harada, Ryuichi; Iwata, Ren; Yanai, Kazuhiko

    2015-07-01

    Histamine is a physiological amine which initiates a multitude of physiological responses by binding to four known G-protein coupled histamine receptor subtypes as follows: histamine H1 receptor (H1 R), H2 R, H3 R, and H4 R. Brain histamine elicits neuronal excitation and regulates a variety of physiological processes such as learning and memory, sleep-awake cycle and appetite regulation. Microglia, the resident macrophages in the brain, express histamine receptors; however, the effects of histamine on critical microglial functions such as chemotaxis, phagocytosis, and cytokine secretion have not been examined in primary cells. We demonstrated that mouse primary microglia express H2 R, H3 R, histidine decarboxylase, a histamine synthase, and histamine N-methyltransferase, a histamine metabolizing enzyme. Both forskolin-induced cAMP accumulation and ATP-induced intracellular Ca(2+) transients were reduced by the H3 R agonist imetit but not the H2 R agonist amthamine. H3 R activation on two ubiquitous second messenger signalling pathways suggests that H3 R can regulate various microglial functions. In fact, histamine and imetit dose-dependently inhibited microglial chemotaxis, phagocytosis, and lipopolysaccharide (LPS)-induced cytokine production. Furthermore, we confirmed that microglia produced histamine in the presence of LPS, suggesting that H3 R activation regulate microglial function by autocrine and/or paracrine signalling. In conclusion, we demonstrate the involvement of histamine in primary microglial functions, providing the novel insight into physiological roles of brain histamine.

  5. Release and systemic accumulation of heavy metals from preformed crowns used in restoration of primary teeth.

    Science.gov (United States)

    Kodaira, Hiroe; Ohno, Kohachiro; Fukase, Naoko; Kuroda, Midori; Adachi, Shiki; Kikuchi, Motohiro; Asada, Yoshinobu

    2013-01-01

    Preformed crowns for restoration of primary teeth are used in various treatments and are essential for restoring the crowns of primary molars. However, there are concerns that mechanical, chemical, and thermal stimulation may cause release of components of such crowns. We examined systemic accumulation of heavy metals associated with preformed crowns (3M Stainless Steel Primary Molar Crowns) used in primary tooth restoration. The participants were 37 children who had visited the Pediatric Dental Clinic of Tsurumi University Dental Hospital. They were divided into two groups: 22 participants without a history of being fitted with a preformed crown for primary tooth restoration (controls), and 15 participants with preformed crowns for primary tooth restoration. Analysis of hair samples showed a significant difference in the level of the trace element Cr - an important component of the preformed crowns - between children with and without preformed crowns, but no significant differences in Fe or Ni levels. Levels of the trace elements Ni, Cr, and Fe were within allowable ranges, indicating that these minerals were not likely to be harmful.

  6. Lipolytic responses induced by intracerebroventricular administration of histamine in the rat.

    Science.gov (United States)

    Bugajski, J; Janusz, Z

    1981-04-01

    Histamine (10-50 microgram) administered intraventricularly in conscious rats induced an increase in serum-free fatty acids. The maximum, significant increase appeared 30-60 min after administration. Histamine H1-receptor antagonists, mepyramine and chloropyramine, when injected 2 h prior to histamine, abolished considerably hyperlipaemic responses to histamine. H2-Receptor antagonists, metiamide and cimetidine, given i.c.v. only moderately diminished histamine-induced hyperlipaemia. Histamine injected i.c.v. also increased serum corticosterone levels considerably. This elevation was prevented significantly by the H1-receptor antagonist, mepyramine, but not by the H2-receptor blocker, cimetidine. It seems likely that histamine given i.c.v. induces lipolysis through the release of ACTH, one of the known lipid-mobilizing hormones. The central lipid-mobilizing mechanism after histamine depends more on activation of H1- than H2-receptors.

  7. 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......, 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...... and a significant increase in the levels of histamine and tryptase. The challenge of subjects not allergic to pollen produced no such response. Azelastine and cetirizine significantly reduced allergen-induced sneezing and the associated increase in histamine and tryptase levels. No significant differences were...

  8. Histamine and Nt-methylhistamine in the circulation during intravenous infusion of histamine in normal volunteers.

    Science.gov (United States)

    Sheinman, B D; Devalia, J L; Wylie, G; Davies, R J

    1988-12-01

    Plasma levels of histamine and Nt-methylhistamine were measured simultaneously by high performance liquid chromatography during the intravenous infusion of histamine acid phosphate in six normal volunteers. Progressive, dose-related increases in plasma histamine were noted, reaching a maximum value of 3.1 +/- 0.14 ng ml-1 corresponding to a maximum infusion rate of 180 ng kg-1 min-1 (means +/- SEM). Increases in plasma histamine were accompanied by a significant dose-related fall in mean diastolic blood pressure (baseline 74.0 +/- 4.4 mm Hg falling to 60.0 +/- 3.3 mm Hg at maximum infusion rate, p less than 0.001) and an increase in pulse rate (baseline 76.3 +/- 2.8 beats min-1 rising to 89.24 beats min-1 at maximum infusion rate, p less than 0.05). All subjects exhibited facial flushing, the threshold plasma histamine level for this effect being 1.3 +/- 0.15 ng ml-1 corresponding to an infusion rate of 60 ng kg-1 min-1. Elevation of plasma Nt-methylhistamine was seen in only one subject, who exhibited a level of 0.5 ng ml-1 at the highest infusion rate. These results suggest that measurements of plasma Nt-methylhistamine are unlikely to provide a useful index of histamine release into the circulation.

  9. [Histamine intolerance - are the criteria of an adverse reaction met?].

    Science.gov (United States)

    Reese, Imke

    2016-06-01

    Searching the internet for an explaination of recurring symptoms, many people come across the so-called histamine intolerance disorder. Also many practitioners like to diagnose this disorder without making sure that reproducibility, a prerequisite for an adverse reaction, is present. Consequently, presumably affected persons are often advised to follow a low-histamine diet. Depending on the source of information, these diets often avoid a huge variety of foods containing more or less histamine, which has a considerable impact on patient quality of life. While most persons benefit from such a diet in the beginning - this might be due to the change in dietary habits or the expectation of symptom improvement by dieting - in the long run the expected loss of symptoms will not happen. Underlying a diminished capacity for histamine degradation, the lack of partial or complete symptom improvement might be due to the fact that endogenous histamine release is responsible for reactions. The role of ingested histamine is discussed controversially. However, it is more than obvious that the histamine content of a certain food alone is not enough to predict its tolerance.If histamine intolerance is suspected, an individual diagnostic and therapeutic procedure is mandatory in order to minimize avoidance and to preserve a high quality of life. Ideally this is done in a close cooperation between allergologists and nutritionists/dieticians.

  10. On histamine and appetites

    Directory of Open Access Journals (Sweden)

    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.

  11. [Effects of controlled release nitrogen fertilizer application on dry matter accumulation and nitrogen balance of summer maize].

    Science.gov (United States)

    Si, Dong-Xia; Cui, Zhen-Ling; Chen, Xin-Ping; Lü, Fu-Tang

    2014-06-01

    Effects of four controlled release nitrogen (N) fertilizers, including two kinds of polyester coated urea (Ncau, CRU) and phosphate (NhnP) and humic acid (NhnF) coated urea on assimilates accumulation and nitrogen balance of summer maize were investigated in a mode of one-time fertilization at the regional N recommended rate. The results showed that the N release curves of the two controlled release fertilizers CRU and Ncau matched well with the summer maize N uptake. Compared with the regional N recommendation rate, CRU could increase maize yield by 4.2% and Ncau could maintain the same yield level. CRU significantly increased the dry matter accumulation rate after anthesis of summer maize, but Ncau markedly increased the dry matter accumulated ratio before anthesis. Meanwhile, CRU could reduce the apparent N losses by 19 kg N x hm(-2) in the case of large precipitation. However, NhnF and NhnP caused the yield losses by 0.1%-8.9%, and enhanced the apparent N losses. Therefore, both CRU and Ncau with one-time fertilization could be a simplified alternative to the "total control, staging regulation" fertilization technique at the regional N recommended rate for summer maize production.

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

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen

    1996-01-01

    from such studies are currently accumulating and suggest that the histamine-2 receptor antagonists have potential beneficial effects in the treatment of certain malignant, autoimmune and skin diseases, either alone or in combination with other drugs. The beneficial effect of histamine-2 receptor...... antagonists as adjuvant single drugs to reduce trauma-, blood transfusion- and sepsis-induced immunosuppression has led to research in combined treatment regimens in major surgery, particularly, of patients operated on for malignant diseases....

  13. MRI monitoring of nanocarrier accumulation and release using Gadolinium-SPIO co-labelled thermosensitive liposomes

    NARCIS (Netherlands)

    Lorenzato, Cyril; Oerlemans, Chris; van Elk, Merel; Geerts, Willie J C|info:eu-repo/dai/nl/149264399; Denis de Senneville, Baudouin; Moonen, Chrit; Bos, Clemens

    2016-01-01

    Encapsulation of anticancer drugs in triggerable nanocarriers can beneficially modify pharmacokinetics and biodistribution of chemotherapeutic drugs, and consequently increase tumor drug concentration and efficacy, while reducing side effects. Thermosensitive liposomes release their contents trigger

  14. Modulation of tryptase secretion from human colon mast cells by histamine

    Institute of Scientific and Technical Information of China (English)

    Shao-Heng He; Hua Xie

    2004-01-01

    AIM: To investigate the ability of histamine to modulate tryptase release from human colon mast cells and the potential mechanisms.METHODS: Enzymatically dispersed cells from human colons were challenged with histamine, anti-IgE or calcium ionophore A23187 (CI), and the cell supernatants after challenge were collected. Tryptase release was determined with a sandwich ELISA procedure.able to induce a "bell" shape dose related release of tryptase from colon mast cells. The maximum release of tryptase was approximately 3.5 fold more than spontaneous release. As little as 10 ng/mL histamine showed a similar potency to 10 μg/mL anti-IgE in induction of tryptase release. Histamine induced release of tryptase initiated at 10 s when histamine (100 ng/mL) was added to cells, gradually increased thereafter, and completed at 5 min, Both pertussis toxin or metabolic inhibitors were able to inhibit histamine induced tryptase release. When histamine and anti-IgE were added to colon mast cells at the same time, the quantity of tryptase released was similar to that induced by anti-IgE alone. The similar results were observed with CI. However, when various concentrations of histamine were incubated with cells for 20 min before adding anti-IgE or CI, the quantity of tryptase released was similar to that was induced by histamine alone.CONCLUSION: Histamine is a potent activator of human colon mast cells, which represents a novel and pivotal selfamplification mechanism of mast cell degranulation.

  15. Histamine content and secretion in basophils and mast cells.

    Science.gov (United States)

    Dvorak, A M

    1998-01-01

    Biochemical determinations of the histamine content and secretion from basophils and mast cells have been available for some time, and much of the complex anatomy of these cellular populations and their release reactions has been documented using the electron microscope. The ultrastructural analyses led to the description of vesicular transport between secretory granules and the plasma membrane as a mechanism for secretion from basophils and mast cells--a process termed piecemeal degranulation. Proof of concepts incorporated in a general degranulation model put forth in 1975 (DVORAK, H.F. and DVORAK, A.M.) requires high magnification imaging of a granule constituent in trafficking vesicles in the process of a stimulated release reaction in which the constituent release is monitored biochemically. Development and application of a new enzyme-affinity method to detect histamine at high magnifications in well-preserved ultrastructural samples have provided the necessary means to establish proof that appropriate secretagogues can stimulate the vesicular transport of histamine in basophils and mast cells during release reactions monitored biochemically. The background information necessary to the understanding of this result is presented here, as well as the development and verification of the diamine oxidase-gold method to image histamine in human mast cell granules as the test system. Also presented are applications using this technology to examine histamine stores and secretion in vitro, in vivo, and ex vivo in human basophils and mast cells and in mouse mast cells. Specifically examined are histamine stores developing in maturing mast cells induced to develop de novo from cultured human cord blood cells, secretagogue-stimulated release and recovery of histamine stores from isolated, purified human lung mast cells ex vivo, cytokine-stimulated degranulation of human skin mast cells and their histamine stores in vivo, piecemeal degranulation of human gut mast cells and

  16. Histamine Induces Vascular Hyperpermeability by Increasing Blood Flow and Endothelial Barrier Disruption In Vivo.

    Science.gov (United States)

    Ashina, Kohei; Tsubosaka, Yoshiki; Nakamura, Tatsuro; Omori, Keisuke; Kobayashi, Koji; Hori, Masatoshi; Ozaki, Hiroshi; Murata, Takahisa

    2015-01-01

    Histamine is a mediator of allergic inflammation released mainly from mast cells. Although histamine strongly increases vascular permeability, its precise mechanism under in vivo situation remains unknown. We here attempted to reveal how histamine induces vascular hyperpermeability focusing on the key regulators of vascular permeability, blood flow and endothelial barrier. Degranulation of mast cells by antigen-stimulation or histamine treatment induced vascular hyperpermeability and tissue swelling in mouse ears. These were abolished by histamine H1 receptor antagonism. Intravital imaging showed that histamine dilated vasculature, increased blood flow, while it induced hyperpermeability in venula. Whole-mount staining showed that histamine disrupted endothelial barrier formation of venula indicated by changes in vascular endothelial cadherin (VE-cadherin) localization at endothelial cell junction. Inhibition of nitric oxide synthesis (NOS) by L-NAME or vasoconstriction by phenylephrine strongly inhibited the histamine-induced blood flow increase and hyperpermeability without changing the VE-cadherin localization. In vitro, measurements of trans-endothelial electrical resistance of human dermal microvascular endothelial cells (HDMECs) showed that histamine disrupted endothelial barrier. Inhibition of protein kinase C (PKC) or Rho-associated protein kinase (ROCK), NOS attenuated the histamine-induced barrier disruption. These observations suggested that histamine increases vascular permeability mainly by nitric oxide (NO)-dependent vascular dilation and subsequent blood flow increase and maybe partially by PKC/ROCK/NO-dependent endothelial barrier disruption.

  17. Intracerebroventricular histamine, but not 48/80, causes posttraining memory facilitation in the rat.

    Science.gov (United States)

    de Almeida, M A; Izquierdo, I

    1988-01-01

    The immediate posttraining intracerebroventricular injection of histamine (1 or 10 ng/rat) facilitated memory both of a stepdown inhibitory avoidance task, and of the habituation of rearing responses to an open field. As previously shown for the avoidance task, the combination of cimetidine (1,000 ng/rat) plus prometazine (1,000 ng/rat), but not each drug on its own, blocked the effect of histamine in the habituation task. The effect of histamine was not shared by the intracerebroventricular administration of the mast cell histamine releaser, 48/80 (0.1 to 100 micrograms/rat). The present findings indicate that the memory facilitatory action of histamine might be general across tasks, and that 48/80-releasable, presumably mast cell, endogenous histamine is probably not involved in memory regulation.

  18. In vivo histamine voltammetry in the mouse premammillary nucleus.

    Science.gov (United States)

    Samaranayake, Srimal; Abdalla, Aya; Robke, Rhiannon; Wood, Kevin M; Zeqja, Anisa; Hashemi, Parastoo

    2015-06-07

    Histamine plays a major role in the mediation of allergic reactions such as peripheral inflammation. This classical monoamine is also a neurotransmitter involved in the central nervous system but its role in this context is poorly understood. Studying histamine neurotransmission is important due to its implications in many neurological disorders. The sensitivity, selectivity and high temporal resolution of fast scan cyclic voltammetry (FSCV) offer many advantages for studying electroactive neurotransmitters. Histamine has previously been studied with FSCV; however, the lack of a robust Faradaic electrochemical signal makes it difficult to selectively identify histamine in complex media, as found in vivo. In this work, we optimize an electrochemical waveform that provides a stimulation-locked and unique electrochemical signal towards histamine. We describe in vitro waveform optimization and a novel in vivo physiological model for stimulating histamine release in the mouse premammillary nucleus via stimulation of the medial forebrain bundle. We demonstrate that a robust signal can be used to effectively identify histamine and characterize its in vivo kinetics.

  19. Rat adipose tissue rapidly accumulates and slowly releases an orally-administered high vitamin D dose

    NARCIS (Netherlands)

    Brouwer, DAJ; van Beek, J; Ferwerda, H; Brugman, AM; van der Klis, FRM; Muskiet, FAJ

    1998-01-01

    We investigated the effect of oral high-dose cholecalciferol on plasma and adipose tissue cholecalciferol and its subsequent release, and on plasma 25-hydroxyvitamin D (25(OH)D). Female Wistar rats (n 126) received 37.5 mu g cholecalciferol/d for 14 d and were subsequently studied for a further 88 d

  20. Release of Periplasmic Nucleotidase Induced by Human Antimicrobial Peptide in E. coli Causes Accumulation of the Immunomodulator Adenosine.

    Directory of Open Access Journals (Sweden)

    Andreia Bergamo Estrela

    Full Text Available Previous work by our group described that human β-defensin-2 induces accumulation of extracellular adenosine (Ado in E. coli cultures through a non-lytic mechanism causing severe plasmolysis. Here, we investigate the presence of AMP as a direct precursor and the involvement of a bacterial enzyme in the generation of extracellular Ado by treated bacteria. Following hBD-2 treatment, metabolites were quantified in the supernatants using targeted HPLC-MS/MS analysis. Microbial growth was monitored by optical density and cell viability was determined by colony forming units counts. Phosphatase activity was measured using chromogenic substrate pNPP. The results demonstrate that defensin-treated E. coli strain W releases AMP in the extracellular space, where it is converted to Ado by a bacterial soluble factor. An increase in phosphatase activity in the supernatant was observed after peptide treatment, similar to the effect of sucrose-induced osmotic stress, suggesting that the periplasmic 5'nucleotidase (5'-NT is released following the plasmolysis event triggered by the peptide. Ado accumulation was enhanced in the presence of Co2+ ion and inhibited by EDTA, further supporting the involvement of a metallo-phosphatase such as 5'-NT in extracellular AMP conversion into Ado. The comparative analysis of hBD-induced Ado accumulation in different E. coli strains and in Pseudomonas aeruginosa revealed that the response is not correlated to the peptide's effect on cell viability, but indicates it might be dependent on the subcellular distribution of the nucleotidase. Taken together, these data shed light on a yet undescribed mechanism of host-microbial interaction: a human antimicrobial peptide inducing selective release of a bacterial enzyme (E. coli 5'-NT, leading to the formation of a potent immunomodulator metabolite (Ado.

  1. BIO-ACCUMULATION AND RELEASE OF MERCURY IN VIGNA MUNGO (L. HEPPER SEEDLINGS

    Directory of Open Access Journals (Sweden)

    Hussain. K

    2010-09-01

    Full Text Available Effect of mercury on the seedling of Vigna mungo seedlings was studied by culturing the seedlings in Hoagland medium artificially contaminated with 5 and 10mM Mercuric Chloride. Histochemical localization of the mercury in shoot and root tissues was done by staining with dithizone and quantitative analyses of mercury content accumulated in root, stem and leaf tissues were done using mercury analyser. Localization of mercury was observed as coloured masses in the cells of root and stem. Stem tissues of seedlings showed anatomical modification in the epidermal cells as trichomes. Patterns of bioaccumulation of mercury was root> stem> leaves revealing feeble translocation to the shoot system. A comparison of residual mercury content retained in the growth medium after sample harvesting and quantity accumulated in the plant body reveals that some quantity of mercury is lost presumably through the trichomes developed on the stem and/ or through stomata of the leaves.

  2. Mast cell-derived TNF-α and histamine modify IL-6 and IL-8 expression and release from cutaneous tumor cells

    DEFF Research Database (Denmark)

    Artuc, Metin; Guhl, Sven; Babina, Magda

    2011-01-01

    The coincidence of skin tumors and elevated mast cell (MC) numbers has been known for many years. However, it has remained controversial whether, in this context, MCs promote or inhibit tumor growth. Addressing this problem, different melanoma and squamous cell carcinoma cell lines were co-cultivated...... with primary, dermal MC for 24 h and gene or protein expression of cytokines tumor necrosis factor (TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL-8) estimated. Co-culture with MCs led to an increase in IL-8 gene expression and IL-8 protein release from melanoma cells and IL-6 and IL-8 gene expression...... and protein release from squamous cell carcinoma cells, respectively. Moreover induction of IL-6 and IL-8 was primarily regulated by MC-derived TNF-α. Our data suggest an interplay between MCs and tumor cells, which results in altered cytokine release and may, thus, have an impact on tumor growth, invasion...

  3. Integrated Codes for Estimating Environmental Accumulation and Individual Dose from Past Hanford Atmospheric Releases: Hanford Environmental Dose Reconstruction Project

    Energy Technology Data Exchange (ETDEWEB)

    Ikenberry, T. A.; Burnett, R. A.; Napier, B. A.; Reitz, N. A.; Shipler, D. B.

    1992-02-01

    Preliminary radiation doses were estimated and reported during Phase I of the Hanford Environmental Dose Reconstruction (HEDR) Project. As the project has progressed, additional information regarding the magnitude and timing of past radioactive releases has been developed, and the general scope of the required calculations has been enhanced. The overall HEDR computational model for computing doses attributable to atmospheric releases from Hanford Site operations is called HEDRIC (Hanford Environmental Dose Reconstruction Integrated Codes). It consists of four interrelated models: source term, atmospheric transport, environmental accumulation, and individual dose. The source term and atmospheric transport models are documented elsewhere. This report describes the initial implementation of the design specifications for the environmental accumulation model and computer code, called DESCARTES (Dynamic EStimates of Concentrations and Accumulated Radionuclides in Terrestrial Environments), and the individual dose model and computer code, called CIDER (Calculation of Individual Doses from Environmental Radionuclides). The computations required of these models and the design specifications for their codes were documented in Napier et al. (1992). Revisions to the original specifications and the basis for modeling decisions are explained. This report is not the final code documentation but gives the status of the model and code development to date. Final code documentation is scheduled to be completed in FY 1994 following additional code upgrades and refinements. The user's guide included in this report describes the operation of the environmental accumulation and individual dose codes and associated pre- and post-processor programs. A programmer's guide describes the logical structure of the programs and their input and output files.

  4. Histamine: a new immunomodulatory player in the neuron-glia crosstalk

    Directory of Open Access Journals (Sweden)

    Sandra M Rocha

    2014-04-01

    Full Text Available Histamine is an amine acting as a major peripheral inflammatory mediator. In the brain, histamine was initially viewed as a neurotransmitter, but new evidences support its involvement in the modulation of innate immune responses. Recently, we showed that histamine modulates microglial migration and cytokine release. Its pleiotropic actions, ranging from neurotransmission to inflammation, highlight histamine as a key player in a vast array of brain physiologic activities and also in the pathogenesis of several neurodegenerative diseases. Herein, we emphasize the role of histamine as a modulator of brain immune reactions, either by acting on invading peripheral immune cells and/or on resident microglial cells. We also unveil the putative involvement of histamine in the microglial-neuronal communication. We first show that histamine modulates the release of inflammatory mediators, namely nitric oxide, by microglia cells. Consequently, the microglia secretome released upon histamine stimulation fosters dopaminergic neuronal death. These data may reveal important new pharmacological applications on the use histamine and antihistamines, particularly in the context of Parkinson’s disease.

  5. Proposal for defining the relevance of drug accumulation derived from single dose study data for modified release dosage forms.

    Science.gov (United States)

    Scheerans, Christian; Heinig, Roland; Mueck, Wolfgang

    2015-03-01

    Recently, the European Medicines Agency (EMA) published the new draft guideline on the pharmacokinetic and clinical evaluation of modified release (MR) formulations. The draft guideline contains the new requirement of performing multiple dose (MD) bioequivalence studies, in the case when the MR formulation is expected to show 'relevant' drug accumulation at steady state (SS). This new requirement reveals three fundamental issues, which are discussed in the current work: first, measurement for the extent of drug accumulation (MEDA) predicted from single dose (SD) study data; second, its relationship with the percentage residual area under the plasma concentration-time curve (AUC) outside the dosing interval (τ) after SD administration, %AUC(τ-∞)SD ; and third, the rationale for a threshold of %AUC(τ-∞)SD that predicts 'relevant' drug accumulation at SS. This work revealed that the accumulation ratio RA,AUC , derived from the ratio of the time-averaged plasma concentrations during τ at SS and after SD administration, respectively, is the 'preferred' MEDA for MR formulations. A causal relationship was derived between %AUC(τ-∞)SD and RA,AUC , which is valid for any drug (product) that shows (dose- and time-) linear pharmacokinetics regardless of the shape of the plasma concentration-time curve. Considering AUC thresholds from other guidelines together with the causal relationship between %AUC(τ-∞)SD and RA,AUC indicates that values of %AUC(τ-∞)SD ≤ 20%, resulting in RA,AUC ≤ 1.25, can be considered as leading to non-relevant drug accumulation. Hence, the authors suggest that 20% for %AUC(τ-∞)SD is a reasonable threshold and selection criterion between SD or MD study designs for bioequivalence studies of new MR formulations.

  6. Accumulation of plutonium in mammalian wildlife tissues following dispersal by accidental-release tests.

    Science.gov (United States)

    Johansen, M P; Child, D P; Caffrey, E A; Davis, E; Harrison, J J; Hotchkis, M A C; Payne, T E; Ikeda-Ohno, A; Thiruvoth, S; Twining, J R; Beresford, N A

    2016-01-01

    We examined the distribution of plutonium (Pu) in the tissues of mammalian wildlife inhabiting the relatively undisturbed, semi-arid former Taranaki weapons test site, Maralinga, Australia. The accumulation of absorbed Pu was highest in the skeleton (83% ± 6%), followed by muscle (10% ± 9%), liver (6% ± 6%), kidneys (0.6% ± 0.4%), and blood (0.2%). Pu activity concentrations in lung tissues were elevated relative to the body average. Foetal transfer was higher in the wildlife data than in previous laboratory studies. The amount of Pu in the gastrointestinal tract was highly elevated relative to that absorbed within the body, potentially increasing transfer of Pu to wildlife and human consumers that may ingest gastrointestinal tract organs. The Pu distribution in the Maralinga mammalian wildlife generally aligns with previous studies related to environmental exposure (e.g. Pu in humans from worldwide fallout), but contrasts with the partitioning models that have traditionally been used for human worker-protection purposes (approximately equal deposition in bone and liver) which appear to under-predict the skeletal accumulation in environmental exposure conditions.

  7. Sensory responses of human skin to synthetic histamine analogues and histamine.

    OpenAIRE

    Davies, M. G.; Greaves, M W

    1980-01-01

    The potential for itch production in human skin of the synthetic analogues of histamine, 2-methyl histamine (an H1-receptor agonist) and 4-methyl histamine and dimaprit (H2-receptor agonists) has been studied in vivo and compared with histamine. Itch thresholds for 2-methyl histamine were consistently much higher than for histamine (P < 0.001). The H1-receptor antagonist chlorpheniramine raised the itch thresholds to 2-methyl histamine and histamine significantly (P < 0.001). Pruritus was not...

  8. Isolation and typification of histamine-producing Lactobacillus vaginalis strains from cheese.

    Science.gov (United States)

    Diaz, Maria; del Rio, Beatriz; Ladero, Victor; Redruello, Begoña; Fernández, María; Martin, Maria Cruz; Alvarez, Miguel A

    2015-12-23

    In food, the biogenic amine (BA) histamine is mainly produced by histidine decarboxylation catalysed by microbial histidine decarboxylase. The consumption of foods containing high concentrations of histamine can trigger adverse neurological, gastrointestinal and respiratory reactions. Indeed, histamine is one of the most toxic of all BAs, and is often detected in high concentration in cheese. However, little is known about the microorganisms responsible for its accumulation in this food. In the present work, 25 histamine-producing Lactobacillus vaginalis strains were isolated from a blue-veined cheese (the first time that histamine-producing strains of this species have been isolated from any food). The restriction profiles of their genomes were analysed by PFGE, and seven lineages identified. The presence of the histidine decarboxylase gene (hdcA) was confirmed by PCR. The nucleotide sequence and genetic organisation of the histamine biosynthesis gene cluster (HDC) and its flanking regions are described for a representative strain (L. vaginalis IPLA11050).

  9. Modulation of bradykinin-induced gastric-cardiovascular reflexes by histamine.

    Science.gov (United States)

    Stebbins, C L; Stahl, G L; Theodossy, S J; Longhurst, J C

    1992-01-01

    Both histamine and bradykinin induce gastric-cardiovascular reflexes and are released during several pathophysiological conditions. This study examined the possibility that histamine modulates the magnitude of the reflex response to stimulation by bradykinin. Thus in chloralose anesthetized cats, the cardiovascular response to stimulation of the gastric serosa with 1 microgram/ml bradykinin was monitored before and after topical application of 100 micrograms/ml histamine (n = 6) or 1 mg/ml diphenhydramine (H1-receptor antagonist) and histamine (n = 5). After application of histamine, bradykinin-induced increases in mean arterial pressure and left ventricular pressure were attenuated by 23 and 27%, respectively. Conversely, when the H1-receptors on the serosal surface of the stomach were blocked (n = 5) before application of histamine, the pressor response to bradykinin was augmented by 26%. To determine the afferents that might contribute to the attenuating effect of histamine, we recorded single unit activity in 14 A delta and 21 C visceral afferent fibers in response to bradykinin stimulation before and after histamine stimulation. We observed that the impulse activity of 10 of the A delta and 14 of the C fibers to bradykinin stimulation was reduced after treatment with histamine. These results suggest that histamine induces an inhibitory effect on the nerve endings of visceral A delta and C fibers to the action of bradykinin through an H1-receptor mechanism. This inhibitory effect attenuates the magnitude of the consequent cardiovascular reflex response.

  10. 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 histamine release. These observations support the view that microtubules may not be directly involved in secretion, but apparently an increased number of microfilaments is associated with a decreased capacity of the mast cells for histamine release. We suggest that microfilaments have to be depolymerized...

  11. Histamine H3 receptors regulate ACTH release by AtT-20 cel ls%组胺H3受体对垂体瘤AtT-20细胞分泌ACTH的调节作用

    Institute of Scientific and Technical Information of China (English)

    谢建军; 罗晓星; 赵德化

    2001-01-01

    AIM To investigate the signal transduction mechanism of histamine H3 r eceptor. METHODS The adrenocorticotropic hormone (ACTH) levels of supernatants on AtT- 20 cells from the pituitary gland tumor were measured by radioimmunoassa y at the given time after histamine agonists were administrated and the effects o f R-(α)-methylhistamine on the cells proliferation were observed. RES ULTS The H3 receptor specific agonist, R-(α)-methylhistamine incre ased the release of A CT H in time-dependent manner. It increased significantly after administrated r e agents 8 h which reached 1920 μg*L-1 compared to the control group 7 80 μg*L-1 . while the H1 receptor agonist 2-methylhistamine and the H2 agonist impro midine were significantly less potent. Furthermore, this response was blocked by thiop eramide, an H3 receptor specific antagonist, but not by the H1 and H2 anta gonist chlorpheniramine and cimetidine. R-(α)- methylhistamine had no significant i nf luence on cell proliferation within 24 h. Pretreatment with N-ethylmaleimide (N EM ) could abolish the effects of R-(α)-methylhistamine on the release of ACTH. CO NCLUSION Specific activation of H3 receptor could evoke the excitatio n-secreti on coupling process, and G protein might be involved in the signal transdu ction.%目的 观察组胺受体激动剂对AtT-20细胞分泌ACTH的影响,并探讨G蛋 白在组胺H3 受体信号转导机制中的作用. 方法 选用文献报道的高表达组胺H3受体 的垂体细胞瘤AtT-20 作为观察系统,用放免分析法测定给予组胺受体激动剂后各时间点细胞上清液中ACTH分泌量 的变化,并观察药物对细胞增殖的影响. 结果 组胺H3受体激动剂R- (α)- MeHA(0.1 μmol*L-1)作用8 h能明显促进ACTH的释放,释放量为1920 μg * L-1,与同时间对照组(780 μg*L-1)相比,明显增高(P<0.01);H 1和H2激动剂则无此作用. 且R-(α)-MeHA引起ACTH分泌 的效应能被H3受体特异

  12. 顺阿曲库铵的药效学及其对组胺释放的影响%Pharmacodynamics and histamine-me-releasing potency of cis-atracurium

    Institute of Scientific and Technical Information of China (English)

    吴新民; 李玲; 刘毓和; 张兰霞

    2010-01-01

    CIS1 than in group ATR.The maximal degree of N-M block was 100%and the intubation condition was excellent in group CIS1 and ATR.There wag no significant difference in the recovery index between group CIS1 and ATR.The onset time was significantly longer and duration of action shorter in group CIS2 than in group CIS1.There was no significant difference in recovery index between group CIS1 and CIS2.There was no significant change in plasma histamine concentration at T1-3 as compared with the baseline at T0 in group CIS1 but plasma histamine concentration was significantly increased at T2,3 in group ATR.MAP was significantly decreased after induction of anesthesia with propofol and remifentanil,but CIS and ATR did not significantly change MAP.Conclusion The onset time is longer and duration of action is shorter after cis-atracurium than afar atracurium.The N-M block induced by cis-atracurium is significantly attenuated if stored at the room temperature.Cis-atracurium does not cause histamine release.

  13. Activation of histamine H3 receptors in human nasal mucosa inhibits sympathetic vasoconstriction.

    Science.gov (United States)

    Varty, LoriAnn M; Gustafson, Eric; Laverty, Maureen; Hey, John A

    2004-01-19

    The peripheral histamine H3 receptor is a presynaptic heterologous receptor located on postganglionic sympathetic nerve fibers innervating sympathetic effector systems such as blood vessels and the heart. An extensive body of evidence shows that activation of the histamine H3 receptor attenuates sympathetic tone by presynaptic inhibition of noradrenaline release. It is proposed that this sympathoinhibitory action, in vivo, leads to reduced vasoconstriction, thereby eliciting a vasodilatory effect. In humans, the peripheral histamine H3 receptor has also been shown to exert a sympathoinhibitory function on specific peripheral autonomic effector systems. For example, human saphenous vein and heart possess functional presynaptic histamine H3 receptors on the sympathetic nerve terminals that upon activation decrease the sympathetic tone to these respective organs. The present studies were conducted to define the role of histamine H3 receptors on neurogenic sympathetic vasoconstrictor responses in human nasal turbinate mucosa. Contractility studies were conducted to evaluate the effect of histamine H3 receptor activation on sympathetic vasoconstriction in surgically isolated human nasal turbinate mucosa. We found that the histamine H3 receptor agonist, (R)-alpha-methylhistamine (30 and 300 nM), inhibited electrical field stimulation-induced (neurogenic) sympathetic vasoconstriction in a concentration-dependent fashion. Pretreatment with the selective histamine H3 receptor antagonist, clobenpropit (100 nM), blocked the sympathoinhibitory effect of (R)-alpha-methylhistamine on the neurogenic sympathetic vasoconstriction. In addition, analysis of Taqman mRNA expression studies showed a specific, high level of distribution of the histamine H3 receptor localized in the human nasal mucosa. Taken together, these studies indicate that histamine H3 receptors modulate vascular contractile responses in human nasal mucosa most likely by inhibiting noradrenaline release from

  14. Histamine and histamine receptor antagonists in cancer biology.

    Science.gov (United States)

    Blaya, Bruno; Nicolau-Galmés, Francesca; Jangi, Shawkat M; Ortega-Martínez, Idoia; Alonso-Tejerina, Erika; Burgos-Bretones, Juan; Pérez-Yarza, Gorka; Asumendi, Aintzane; Boyano, María D

    2010-07-01

    Histamine has been demonstrated to be involved in cell proliferation, embryonic development, and tumour growth. These various biological effects are mediated through the activation of specific histamine receptors (H1, H2, H3, and H4) that differ in their tissue expression patterns and functions. Although many in vitro and in vivo studies of the modulatory roles of histamine in tumour development and metastasis have been reported, the effect of histamine in the progression of some types of tumours remains controversial; however, recent findings on the role of histamine in the immune system have shed new light on this question. This review focuses on the recent advances in understanding the roles of histamine and its receptors in tumour biology. We report our recent observations of the anti-tumoural effect of H1 histamine antagonists on experimental and human melanomas. We have found that in spite of exogenous histamine stimulated human melanoma cell proliferation, clonogenic ability and migration activity in a dose-dependent manner, the melanoma tumour growth was not modulated by in vivo histamine treatment. On the contrary, terfenadine-treatment in vitro induced melanoma cell death by apoptosis and in vivo terfenadine treatment significantly inhibited tumour growth in murine models. These observations increase our understanding of cancer biology and may inspire novel anticancer therapeutic strategies.

  15. Contents, accumulation and release of energy in green, dead and decomposing plant materials in an upland grassland near Kamenicky, Czechoslovakia.

    Science.gov (United States)

    Ulehlová, B

    1980-01-01

    The energy content was studied in above-ground live plant material and in litter in a natural grassland ecosystem with dominant Nardus stricta L., defined phytosociologically as Polygalo-Nardetum strictae. PREISING 1950 corr. OBERDORFER 1957, and in two of its fertilized variants in the course of 1975 to 1977. Based on the determined production characteristics and data on decomposition processes, the amounts of energy accumulated by the green parts of the stands and the amount of energy released during decomposition from the litter were calculated. Changes in the energy content of litter in different stages of decomposition were determined. With progressing decomposition the energy content per gram ash-free decomposing plant litter increases.

  16. Histamine and substance P in synovial fluid of patients with temporomandibular disorders.

    Science.gov (United States)

    Li, W; Long, X; Jiang, S; Li, Y; Fang, W

    2015-05-01

    Although psychosocial factors and malocclusion are regarded as potential causes of temporomandibular disorders (TMD), the underlying pathogenesis is poorly understood. Recent studies suggest that substance P (SP), which has been associated with both psychosocial factors and malocclusion, and histamine, whose release can be induced by SP, may be implicated in the pathogenetic process. This study was designed to measure the concentration of histamine and SP in synovial fluid (SF) of both 38 patients with TMD and 11 healthy controls, and analyse the correlation between histamine and SP. Patients with TMD were divided into three subgroups: displaced disc with reduction (DDR), displaced disc without reduction (DDNR) and osteoarthritis (OA), with 10, 13, 15 subjects in every subgroup, respectively. After collecting SF samples, histamine and SP levels were measured by enzyme-linked immunosorbent assay analysis (ELISA) and calibrated by bicinchoninic acid (BCA)-quantified protein level in the samples. The results suggest that OA group presented a significantly higher level of both histamine and SP than DDNR, DDR and healthy control groups. Histamine or SP in DDR and DDNR groups tend to be higher than control group, but no significance was found. Painful TMJs show higher histamine and SP than painless TMJs. Correlation analysis reveals a significant correlation between histamine and SP concentrations. Collectively, this study showed the changes of histamine and SP in the SF from different stages of TMD and found a significant correlation between the two substances, suggesting their potential implication in the pathogenesis of TMD.

  17. Therapeutic potential of histamine H3 receptor agonist for the treatment of obesity and diabetes mellitus.

    Science.gov (United States)

    Yoshimoto, Ryo; Miyamoto, Yasuhisa; Shimamura, Ken; Ishihara, Akane; Takahashi, Kazuhiko; Kotani, Hidehito; Chen, Airu S; Chen, Howard Y; Macneil, Douglas J; Kanatani, Akio; Tokita, Shigeru

    2006-09-12

    Histamine H3 receptors (H3Rs) are located on the presynaptic membranes and cell soma of histamine neurons, where they negatively regulate the synthesis and release of histamine. In addition, H3Rs are also located on nonhistaminergic neurons, acting as heteroreceptors to regulate the releases of other amines such as dopamine, serotonin, and norepinephrine. The present study investigated the effects of H3R ligands on appetite and body-weight regulation by using WT and H3R-deficient mice (H3RKO), because brain histamine plays a pivotal role in energy homeostasis. The results showed that thioperamide, an H3R inverse agonist, increases, whereas imetit, an H3R agonist, decreases appetite and body weight in diet-induced obese (DiO) WT mice. Moreover, in DiO WT mice, but not in DiO H3RKO mice, imetit reduced fat mass, plasma concentrations of leptin and insulin, and hepatic triglyceride content. The anorexigenic effects of imetit were associated with a reduction in histamine release, but a comparable reduction in histamine release with alpha-fluoromethylhistidine, an inhibitor of histamine synthesis, increased appetite. Moreover, the anorexigenic effects of imetit were independent of the melanocortin system, because imetit comparably reduced appetite in melanocortin 3 and 4 receptor-deficient mice. The results provide roles of H3Rs in energy homeostasis and suggest a therapeutic potential for H3R agonists in the treatment of obesity and diabetes mellitus.

  18. Therapeutic potential of histamine H3 receptor agonist for the treatment of obesity and diabetes mellitus

    OpenAIRE

    YOSHIMOTO, Ryo; Miyamoto, Yasuhisa; Shimamura, Ken; Ishihara, Akane; Takahashi, Kazuhiko; Kotani, Hidehito; Chen, Airu S.; Chen, Howard Y.; MacNeil, Douglas J.; Kanatani, Akio; Tokita, Shigeru

    2006-01-01

    Histamine H3 receptors (H3Rs) are located on the presynaptic membranes and cell soma of histamine neurons, where they negatively regulate the synthesis and release of histamine. In addition, H3Rs are also located on nonhistaminergic neurons, acting as heteroreceptors to regulate the releases of other amines such as dopamine, serotonin, and norepinephrine. The present study investigated the effects of H3R ligands on appetite and body-weight regulation by using WT and H3R-deficient mice (H3RKO)...

  19. Histamine H3 receptor antagonist decreases cue-induced alcohol reinstatement in mice.

    Science.gov (United States)

    Nuutinen, Saara; Mäki, Tiia; Rozov, Stanislav; Bäckström, Pia; Hyytiä, Petri; Piepponen, Petteri; Panula, Pertti

    2016-07-01

    We have earlier found that the histamine H3 receptor (H3R) antagonism diminishes motivational aspects of alcohol reinforcement in mice. Here we studied the role of H3Rs in cue-induced reinstatement of alcohol seeking in C57BL/6J mice using two different H3R antagonists. Systemic administration of H3R antagonists attenuated cue-induced alcohol seeking suggesting that H3R antagonists may reduce alcohol craving. To understand how alcohol affects dopamine and histamine release, a microdialysis study was performed on C57BL/6J mice and the levels of histamine, dopamine and dopamine metabolites were measured in the nucleus accumbens. Alcohol administration was combined with an H3R antagonist pretreatment to reveal whether modulation of H3R affects the effects of alcohol on neurotransmitter release. Alcohol significantly increased the release of dopamine in the nucleus accumbens but did not affect histamine release. Pretreatment with H3R antagonist ciproxifan did not modify the effect of alcohol on dopamine release. However, histamine release was markedly increased with ciproxifan. In conclusion, our findings demonstrate that H3R antagonism attenuates cue-induced reinstatement of alcohol seeking in mice. Alcohol alone does not affect histamine release in the nucleus accumbens but H3R antagonist instead increases histamine release significantly suggesting that the mechanism by which H3R antagonist inhibits alcohol seeking found in the present study and the decreased alcohol reinforcement, reward and consumption found earlier might include alterations in the histaminergic neurotransmission in the nucleus accumbens. These findings imply that selective antagonists of H3Rs could be a therapeutic strategy to prevent relapse and possibly diminish craving to alcohol use. This article is part of the Special Issue entitled 'Histamine Receptors'.

  20. [Antibacterial activity of essential oil vapor for histamine-producing bacteria].

    Science.gov (United States)

    Kamii, Eri; Terada, Gaku; Akiyama, Junki; Isshiki, Kenji

    2011-01-01

    In this study, we evaluated the antibacterial activity of essential oil vapors against histamine-producing bacteria Morganella morganii NBRC3848 and Raultella planticola NBRC3317. We measured the minimum inhibitory dose (MID) of 14 essential oils towards these two strains. Allyl isothiocyanate (AIT) and salicylaldehyde (SA) vapors showed higher antibacterial activity than the other 12 essential oil vapors. Both AIT and SA vapors suppressed growth of total aerobic bacteria and histamine-producing bacteria in bigeye tuna and mackerel meat during storage at 12°C. These vapors also inhibited histamine accumulation in bigeye tuna meat and mackerel meat. Thus, application of AIT and SA vapors is effective for preventing increase of histamine-producing bacteria and histamine formation in fish meat.

  1. Modulation of ConA-induced inflammatory ascites by histamine - short communication.

    Science.gov (United States)

    Baintner, Károly

    2015-03-01

    The early phase of the ConA-induced inflammatory ascites was studied, with special reference to histamine. Concanavalin A (ConA), a cell-surface binding lectin was injected i.p. (25 mg/kg bw) to mice. After 1 h the animals were killed, the ascitic fluid collected and measured. Other agents were injected s.c., 10 min before the ConA-challenge. Exogenous histamine markedly inhibited the ConA-induced ascites. Release of endogenous vasoactive agents from the mast cells by Compound 48/80 had a similar, but slight effect. Cromolyn, a mast cell stabilizing agent, and chloropyramine, a histamine H1 receptor antagonist was ineffective. Although histamine increases endothelial permeability, it did not enhance the formation of ascitic fluid, on the contrary, it inhibited the ConA-induced ascites, presumably due to its known hypotonic effect. It is concluded that ConA-induced ascites is not mediated by mast cell histamine.

  2. The histamine H3 receptor and eating behavior.

    Science.gov (United States)

    Passani, Maria Beatrice; Blandina, Patrizio; Torrealba, Fernando

    2011-01-01

    Interest in the histaminergic system as a potential target for the treatment of feeding disorders is driven by the unsatisfactory history of the pharmacotherapy of obesity. Eating behavior is regulated by a complex interplay of central neurotransmitter systems, peripheral endocrine stimuli, the circadian rhythm, and environmental cues, all factors that change the behavioral state and alter homeostatic aspects of appetite and energy expenditure. Key factors driving eating behavior are appetite and satiety that are regulated through different mechanisms. Brain histamine has long been considered a satiety signal in the nervous system. Recent observations, however, indicate that histamine does not meet the criteria for being a satiety signal, because augmented histamine release accompanies the appetitive phase of feeding behavior rather than food consumption and satiety. The appetitive phase requires a high and yet optimal arousal state, and the histaminergic system is crucial for sustaining a high degree of arousal during motivated behavior. Histamine H(1) receptors in the brain are crucial for the regulation of the diurnal rhythm of food intake and the regulation of obesity; however, from a therapeutic standpoint, no brain-penetrating H(1) receptor agonists have been identified that would have antiobesity effects. Despite conflicting preclinical data, insights are emerging into the potential role of histamine H(3) receptors as a target of antiobesity therapeutics. The aim of this review is to outline the relevance of the histaminergic system in controlling feeding behavior and evaluate the potential therapeutic use of histaminergic ligands for the treatment of eating disorders.

  3. Histamine Neurons In The Tuberomamillary Nucleus: A Whole Center Or Distinct Subpopulations?

    Directory of Open Access Journals (Sweden)

    Patrizio eBlandina

    2012-05-01

    Full Text Available Histamine axons originate from a single source, the tuberomamillary nucleus of the posterior hypothalamus, to innervate almost all CNS regions. This feature, a compact cell group with widely distributed fibers, resembles that of other amines systems, such as noradrenaline or serotonin, and is consistent with a function for histamine over a host of physiological processes, including the regulation of the sleep-wake cycle, appetite, endocrine homeostasis, body temperature, pain perception, learning, memory and emotion. An important question is whether these diverse physiological roles are served by different histamine neuronal subpopulation. While the histamine system is generally regarded as one single functional unit that provides histamine throughout the brain, evidence is beginning to accumulate in favour of heterogeneity of the histamine neurons. The aim of this review is to summarize experimental evidence demonstrating that histamine neurons are heterogeneous, organized into functionally distinct circuits, impinging on different brain regions, and displaying selective control mechanisms. This could imply independent functions of subsets of histamine neurons according to their respective origin and terminal projections.

  4. Histamine in the locus coeruleus promotes descending noradrenergic inhibition of neuropathic hypersensitivity.

    Science.gov (United States)

    Wei, Hong; Jin, Cong-Yu; Viisanen, Hanna; You, Hao-Jun; Pertovaara, Antti

    2014-12-01

    Among brain structures receiving efferent projections from the histaminergic tuberomammillary nucleus is the pontine locus coeruleus (LC) involved in descending noradrenergic control of pain. Here we studied whether histamine in the LC is involved in descending regulation of neuropathic hypersensitivity. Peripheral neuropathy was induced by unilateral spinal nerve ligation in the rat with a chronic intracerebral and intrathecal catheter for drug administrations. Mechanical hypersensitivity in the injured limb was assessed by monofilaments. Heat nociception was assessed by determining radiant heat-induced paw flick. Histamine in the LC produced a dose-related (1-10μg) mechanical antihypersensitivity effect (maximum effect at 15min and duration of effect 30min), without influence on heat nociception. Pretreatment of LC with zolantidine (histamine H2 receptor antagonist), but not with pyrilamine (histamine H1 receptor antagonist), and spinal administration of atipamezole (an α2-adrenoceptor antagonist), prazosine (an α1-adrenoceptor antagonist) or bicuculline (a GABAA receptor antagonist) attenuated the antihypersensitivity effect of histamine. The histamine-induced antihypersensitivity effect was also reduced by pretreatment of LC with fadolmidine, an α2-adrenoceptor agonist inducing autoinhibition of noradrenergic cell bodies. Zolantidine or pyrilamine alone in the LC failed to influence pain behavior, while A-960656 (histamine H3 receptor antagonist) suppressed hypersensitivity. A plausible explanation for these findings is that histamine, due to excitatory action mediated by the histamine H2 receptor on noradrenergic cell bodies, promotes descending spinal α1/2-adrenoceptor-mediated inhibition of neuropathic hypersensitivity. Blocking the autoinhibitory histamine H3 receptor on histaminergic nerve terminals in the LC facilitates release of histamine and thereby, increases descending noradrenergic pain inhibition.

  5. Histamine 50-Skin-Prick Test: A Tool to Diagnose Histamine Intolerance

    OpenAIRE

    Lukas Kofler; Hanno Ulmer; Heinz Kofler

    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 ...

  6. Improgan antinociception does not require neuronal histamine or histamine receptors.

    Science.gov (United States)

    Izadi Mobarakeh, Jalal; Nalwalk, Julia W; Watanabe, Takeshi; Sakurada, Shinobu; Hoffman, Marcel; Leurs, Rob; Timmerman, Henk; Silos-Santiago, Immaculada; Yanai, Kazuhiko; Hough, Lindsay B

    2003-06-06

    Improgan, a chemical congener of the H(2) antagonist cimetidine, induces antinociception following intracerebroventricular (i.c.v.) administration in rodents, but the mechanism of action of this compound remains unknown. Because the chemical structure of improgan closely resembles those of histamine and certain histamine blockers, and because neuronal histamine is known to participate in pain-relieving responses, the antinociceptive actions of improgan were evaluated in mice containing null mutations in the genes for three histamine receptors (H(1), H(2), and H(3)) and also in the gene for histidine decarboxylase (the histamine biosynthetic enzyme). Similar to earlier findings in Swiss-Webster mice, improgan induced maximal, reversible, dose-related reductions in thermal nociceptive responses in ICR mice, but neither pre-improgan (baseline) nor post-improgan nociceptive latencies were changed in any of the mutant mice as compared with wild-type controls. Improgan also had weak inhibitory activity in vitro (pK(i)=4.7-4.9) on specific binding to three recently-discovered, recombinant isoforms of the rat H(3) receptor (H(3A), H(3B), and H(3C)). The present findings strongly support the hypothesis that neuronal histamine and its receptors fail to play a role in improgan-induced antinociception.

  7. Histamine production by Enterobacter aerogenes in chub mackerel (Scomber japonicus) at various storage temperatures

    OpenAIRE

    Zou, Yu; Hou, Xiyan

    2016-01-01

    Abstract Growth of Enterobacter aerogenes and accumulation of histamine in chub mackerel (Scomber japonicus) were investigated through measuring bacterial count, histidine decarboxylase (HDC) activity and histamine content in fish samples stored at various temperatures from 4 to 37 °C. Results showed that bacterial count and HDC activity rapidly increased in chub mackerel inoculated with E. aerogenes at storage temperature above 20 °C and reached the highest values (8.64 log CFU/g and 31.68 U...

  8. Histamine H3 receptor activation inhibits neurogenic sympathetic vasoconstriction in porcine nasal mucosa.

    Science.gov (United States)

    Varty, LoriAnn M; Hey, John A

    2002-10-11

    Histamine release from mast cells is a primary mediator of rhinorrhea, nasal mucosal swelling, increased secretion, sneezing, pruritus and congestion that occur in allergic rhinitis. It is well known that histamine H(1) receptor antagonists inhibit the itch and rhinorhea, but do not block the allergic nasal congestion. A growing body of evidence shows that in addition to histamine H(1) receptors, activation of H(3) receptors may contribute to the procongestant nasal actions of histamine. Activation of the prejunctional histamine H(3) receptor modulates sympathetic control of nasal vascular tone and resistance. The present study was conducted to further characterize the role of histamine H(3) receptors on neurogenic sympathetic vascular contractile responses in isolated porcine nasal turbinate mucosa. We presently found that the histamine H(3) receptor agonist, (R)-alpha-methylhistamine (10-1000 nM), inhibited electrical field stimulation-induced sympathetic vasomotor contractions in a concentration-dependent fashion. Pretreatment with either of the selective histamine H(3) receptor antagonists, thioperamide and clobenpropit, blocked the sympathoinhibitory effect of (R)-alpha-methylhistamine in porcine turbinate mucosa. The effect of compound 48/80, an agent that elicits the release of endogenous histamine from mast cells on nasal sympathetic contractile responses, was also tested. The action of compound 48/80 to release mast cell-derived histamine in the nose mimics many of the nasal responses associated with allergic rhinitis, extravascular leakage and decreased nasal patency. We presently found that compound 48/80 also inhibited the electrical field stimulation-induced sympathetic response. Pretreatment with the H(3) receptor antagonist clobenpropit blocked the sympathoinhibitory action of compound 48/80 on sympathetic contractile responses in nasal mucosa. Taken together, these studies indicate that histamine H(3) receptors modulate vascular contractile

  9. Increased brain histamine H3 receptor expression during hibernation in golden-mantled ground squirrels

    Directory of Open Access Journals (Sweden)

    Anichtchik Oleg V

    2003-09-01

    Full Text Available Abstract Background Hibernation is a state of extremely reduced physiological functions and a deep depression of CNS activity. We have previously shown that the histamine levels increase in the brain during hibernation, as does the ratio between histamine and its first metabolite, suggesting increased histamine turnover during this state. The inhibitory histamine H3 receptor has both auto- and heteroreceptor function, rendering it the most likely histamine receptor to be involved in regulating the activity of histamine as well as other neurotransmitters during hibernation. In view of accumulating evidence that there is a global depression of transcription and translation during hibernation, of all but a few proteins that are important for this physiological condition, we reasoned that an increase in histamine H3 receptor expression would clearly indicate an important hibernation-related function for the receptor. Results In this study we show, using in situ hybridization, that histamine H3 receptor mRNA increases in the cortex, caudate nucleus and putamen during hibernation, an increase that is accompanied by elevated receptor binding in the cerebral cortex, globus pallidus and substantia nigra. These results indicate that there is a hibernation-related increase in H3 receptor expression in cortical neurons and in striatopallidal and striatonigral GABAergic neurons. GTP-γ-S binding autoradiography shows that the H3 receptors in the globus pallidus and substantia nigra can be stimulated by histamine throughout the hibernation cycle, suggesting that they are functionally active during hibernation. Conclusions These results show that the histamine H3 receptor gene is one of the few with a transcript that increases during hibernation, indicating an important role for the receptor in regulating this state. Moreover, the receptor is functionally active in the basal ganglia, suggesting a function for it in regulating e.g. dopaminergic transmission

  10. Signaling mechanism underlying the histamine-modulated action of hypoglossal motoneurons.

    Science.gov (United States)

    Liu, Zi-Long; Wu, Xu; Luo, Yan-Jia; Wang, Lu; Qu, Wei-Min; Li, Shan-Qun; Huang, Zhi-Li

    2016-04-01

    Histamine, an important modulator of the arousal states of the central nervous system, has been reported to contribute an excitatory drive at the hypoglossal motor nucleus to the genioglossus (GG) muscle, which is involved in the pathogenesis of obstructive sleep apnea. However, the effect of histamine on hypoglossal motoneurons (HMNs) and the underlying signaling mechanisms have remained elusive. Here, whole-cell patch-clamp recordings were conducted using neonatal rat brain sections, which showed that histamine excited HMNs with an inward current under voltage-clamp and a depolarization membrane potential under current-clamp via histamine H1 receptors (H1Rs). The phospholipase C inhibitor U-73122 blocked H1Rs-mediated excitatory effects, but protein kinase A inhibitor and protein kinase C inhibitor did not, indicating that the signal transduction cascades underlying the excitatory action of histamine on HMNs were H1R/Gq/11 /phospholipase C/inositol-1,4,5-trisphosphate (IP3). The effects of histamine were also dependent on extracellular Na(+) and intracellular Ca(2+), which took place via activation of Na(+)-Ca(2+) exchangers. These results identify the signaling molecules associated with the regulatory effect of histamine on HMNs. The findings of this study may provide new insights into therapeutic approaches in obstructive sleep apnea. We proposed the post-synaptic mechanisms underlying the modulation effect of histamine on hypoglossal motoneuron. Histamine activates the H1Rs via PLC and IP3, increases Ca(2+) releases from intracellular stores, promotes Na(+) influx and Ca(2+) efflux via the NCXs, and then produces an inward current and depolarizes the neurons. Histamine modulates the excitability of HMNs with other neuromodulators, such as noradrenaline, serotonin and orexin. We think that these findings should provide an important new direction for drug development for the treatment of obstructive sleep apnea.

  11. Histamine from Brain Resident MAST Cells Promotes Wakefulness and Modulates Behavioral States

    OpenAIRE

    Sachiko Chikahisa; Tohru Kodama; Atsushi Soya; Yohei Sagawa; Yuji Ishimaru; Hiroyoshi Séi; Seiji Nishino

    2013-01-01

    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 espec...

  12. The histamine H3 receptor: from discovery to clinical trials with pitolisant

    OpenAIRE

    Schwartz, Jean-Charles

    2011-01-01

    The third histamine receptor was discovered in 1983 by a traditional pharmacological approach, consisting of assessing the inhibitory effect of histamine on its own release from depolarized rat brain slices. The same in vitro test was used to design, in 1987, the first highly selective and potent H3-autoreceptor ligands, the antagonist thioperamide and the agonist (R)alphamethylhistamine which enhances and inhibits, respectively, the activity of histaminergic neurons in brain. The use of thes...

  13. Influence of action of coal dust on metabolism of histamine and serotonin in the body (clinical and experimental study)

    Energy Technology Data Exchange (ETDEWEB)

    Gridneva, N.V.; Dainega, V.G.; Talakin, Yu.N.

    1982-04-01

    Because of the role assigned to the destruction of the metabolism of biogenic amines in the pathogenesis of pneumoconiosis in miners and lack of information on metabolism of histamine and serotonin in first contact with coal dust, it was considered expedient to study peculiarities of their metabolism in the development of dust-induced lung pathology. A table shows results of a clinical study of the changes in the indicators of histamine and serotonin metabolism in miners with pneumoconiosis, those with a long period of service and a healthy control group. Miners with various forms of pneumoconiosis all show a significant increase in the histamine level of blood which may be related to the development in the presence of dust-induced lung disease of autoimmune processes accompanied by the liberation of free histamine from cells. With the increase in histamine, an increase of serotonin appears in blood of diseased miners. Long exposure to dust inflow activates metabolism of serotonin. In addition to the clinical study of diseased miners, an experimental investigation was made of the content of serotonin and histamine in organs of white rats. Table 2 shows that after introduction of coal dust over 1-4 months, the accumulation of serotonin in lungs, brain, kidneys, liver, and small intestine increased and the accumulation of histamine in liver, kidneys and brain decreased. Inhalation of dust produces a greater change in content of serotonin in organs; the intratracheal introduction of dust changes content of histamine. Results of experiment confirm destruction of metabolism of histamine and serotonin by coal/rock dust which proves need to use antiserotonins to cure lung disease. High content of histamine in blood determines need for use of antihistamine preparations especially in the presence of bronchospasms caused by effect of histamine on smooth muscle of bronchi.

  14. Blood-brain barrier to peptides: (/sup 3/H)gonadotropin-releasing hormone accumulation by eighteen regions of the rat brain and by anterior pituitary

    Energy Technology Data Exchange (ETDEWEB)

    Ermisch, A.; Ruehle, H.J. (Karl-Marx-Universitaet, Leipzig (German Democratic Republic). Sektion Biowissenschaften); Klauschenz, E.; Kretzschmar, R. (Akademie der Wissenschaften der DDR, Berlin. Inst. fuer Wirkstofforschung)

    1984-01-01

    After intracarotid injection of (/sup 3/H)gonadotropin-releasing hormone ((/sup 3/H)GnRH) the mean accumulation of radioactivity per unit wet weight of 18 brain samples investigated and the anterior pituitary was 0.38 +- 0.11% g/sup -1/ of the injected tracer dose. This indicates a low but measurable brain uptake of the peptide. The brain uptake of (/sup 3/H)GnRH in blood-brain barrier (BBB)-protected regions is 5% of that of separately investigated (/sup 3/H)OH. In BBB-free regions the accumulation of radioactivity was more than 25-fold higher than in BBB-protected regions. The accumulation of (/sup 3/H)GnRH among regions with BBB varies less than among regions with leaky endothelia. The data presented for (/sup 3/H)GnRH are similar to those for other peptides so far investigated.

  15. Histamine production by Enterobacter aerogenes in sailfish and milkfish at various storage temperatures.

    Science.gov (United States)

    Tsai, Yung-Hsiang; Chang, Shiou-Chung; Kung, Hsien-Feng; Wei, Cheng-I; Hwang, Deng-Fwu

    2005-08-01

    Enterobacter aerogenes was studied for its growth and ability to promote the formation of total volatile base nitrogen (TVBN) and histamine in sailfish (Istiophorus platypterus) and milkfish (Chanos chanos) stored at various temperatures from -20 to 37 degrees C. The optimal temperature for bacterial growth in both fish species was 25 degrees C, whereas the optimal temperature for histamine formation was 37 degrees C. The two fish species inoculated with E. aerogenes, when not properly stored at low temperatures such as 15 degrees C for 36 h, formed histamine at above the U.S. Food and Drug Administration hazardous guideline level of 50 mg/100 g. Milkfish was a better substrate than sailfish for histamine formation by bacterial histidine decarboxylation at elevated temperatures (> 15 degrees C). Although higher contents of TVBN were detected in the spiked sailfish than milkfish during the same storage time at temperatures above 15 degrees C, the use of the 30-mg/100 g level of TVBN as a determination index for fish quality and decomposition was not a good criterion for assessing potential histamine hazard for both fish species. Bacterial growth was controlled by cold storage of the fish at 4 degrees C or below, but histamine formation was stopped only by frozen storage. Once the frozen fish samples were thawed and stored at 25 degrees C, histamine started to accumulate rapidly and reached levels greater than the hazardous action level in 36 h.

  16. Brain-derived mast cells could mediate histamine-induced inhibition of food intake in neonatal chicks.

    Science.gov (United States)

    Kawakami, S; Bungo, T; Ohgushi, A; Ando, R; Shimojo, M; Masuda, Y; Denbow, D M; Furuse, M

    2000-02-28

    In the present study, the effect of intracerebroventricular (i.c.v.) administration of histamine on food intake of neonatal chicks was examined over 2 h. Histamine (100, 200 or 400 nmol, respectively) was injected in the lateral ventricle of 2-day-old chicks, and cumulative food intakes were measured. i.c.v. injection of histamine significantly inhibited food intake in a dose-dependent manner. In addition, compound 48/80, which causes degranulation of mast cells and release of histamine, or thioperamide, which is an antagonist of the histamine H3 autoreceptor and increases histamine release from histaminergic nerve terminals, was injected i.c.v. to clarify whether mast cell- or neuron-derived histamine in the central nervous system of chicks is essential to the feeding inhibition. Central administration of compound 48/80 inhibited food intake with a dose-dependent manner, but thioperamide had no effect on feeding. An inhibitor of mast cell degranulation, sodium cromoglycate, somewhat attenuated food intake inhibited by compound 48/80. These results suggest that brain-derived mast cells could be a major source of histamine in the inhibition of food intake of neonatal chicks.

  17. Histamine 2 blocker potentiates the effects of histamine 1 blocker in suppressing histamine-induced wheal

    Directory of Open Access Journals (Sweden)

    Dhanya N

    2008-01-01

    Full Text Available Background : Histamine is responsible for the wheal and flare reaction in various allergic conditions. Classical antihistamines are the drugs which block the H 1 receptors and are widely used in various allergic conditions, whereas H 2 blockers are mainly used for acid peptic disease. Although H 1 receptor-mediated actions of histamine are primarily responsible for vasodilatation, vasopermeability, and itching, it has been observed that combined blocking of both H 1 and H 2 receptors may provide better relief. Aim: To compare the efficacy of levocetirizine (H 1 blocker versus levocetirizine and ranitidine (H 2 blocker in suppressing histamine-induced wheal. Methods: Fifteen volunteers were given a single dose of levocetirizine 5 mg on day 1 and a single dose of levocetirizine 5 mg with ranitidine 150 mg twice a day on day 7. A pretest was performed by intradermal histamine prick test. After administration of the drugs, the prick test was repeated at 1 hour, 2, 3, 6, and 24 hours, and the size of the wheal measured and statistically analyzed. Results: At 1 hour, there was no statistically significant difference in the wheal size between levocetirizine alone and the combination of levocetirizine and ranitidine. Levocetirizine with ranitidine resulted in statistically significant reduction of wheal size at 2, 3, 6, and 24 hours when compared with levocetirizine alone. Conclusion: H2 blocker potentiates the effects of an H1 blocker in suppressing histamine-induced wheal.

  18. Histamine production by Enterobacter aerogenes in chub mackerel (Scomber japonicus at various storage temperatures

    Directory of Open Access Journals (Sweden)

    Yu ZOU

    2016-01-01

    Full Text Available Abstract Growth of Enterobacter aerogenes and accumulation of histamine in chub mackerel (Scomber japonicus were investigated through measuring bacterial count, histidine decarboxylase (HDC activity and histamine content in fish samples stored at various temperatures from 4 to 37 °C. Results showed that bacterial count and HDC activity rapidly increased in chub mackerel inoculated with E. aerogenes at storage temperature above 20 °C and reached the highest values (8.64 log CFU/g and 31.68 U/g at 37 °C. Meanwhile, fish samples stored at 25 and 37 °C for 18 h, formed histamine at above 50 mg/100 g of the potential hazard level. In contrast, bacterial growth and histamine formation were controlled for 36 h by cold storage at low temperature (4 °C. Therefore, strict temperature control was necessary for preservation and processing of chub mackerel in order to assure this marine fish safety.

  19. Forest Gaps Inhibit Foliar Litter Pb and Cd Release in Winter and Inhibit Pb and Cd Accumulation in Growing Season in an Alpine Forest.

    Directory of Open Access Journals (Sweden)

    Jie He

    Full Text Available The release of heavy metals (such as Pb and Cd from foliar litter play an important role in element cycling in alpine forest ecosystems. Although natural forest gaps could play important roles in the release of heavy metals from foliar litter by affecting the snow cover during the winter and solar irradiation during the growing season, few studies have examined these potential roles. The objectives of this study were to document changes in Pb and Cd dynamics during litter decomposition in the center of gaps and under closed canopies and to investigate the factors that controlled these changes during the winter and growing seasons.Senesced foliar litter from six dominant species, including Kangding willow (Salix paraplesia, Masters larch (Larix mastersiana, Mingjiang fir (Abies faxoniana, Alpine azalea (Rhododendron lapponicum, Red birch (Betula albosinensis and Mourning cypress (Sabina saltuaria, was placed in litterbags and incubated between the gap center and closed canopy conditions in an alpine forest in the eastern region of the Tibetan Plateau. The litterbags were sampled at the snow formation stage, snow coverage stage, snow melt stage and during the growing season. The Pb and Cd concentrations in the sampled foliar litter were determined by acid digestion (HNO3/HClO4.Over one year of decomposition, Pb accumulation and Cd release from the foliar litter occurred, regardless of the foliar litter species. However, Pb and Cd were both released from the foliar litter during the winter and accumulated during the growing season. Compared with the gap center and the canopy gap edge, the extended gap edge and the closed canopy showed higher Pb and Cd release rates in winter and higher Pb and Cd accumulation rates during the growing season, respectively. Statistical analyses indicate that the dynamics of Pb were significantly influenced by frequent freeze-thaw cycles in winter and appropriate hydrothermal conditions during the growing season, the

  20. The in vivo effects of interleukin-3 on histamine levels in non-Hodgkin's lymphoma patients.

    Science.gov (United States)

    Hovgaard, D J; Stahl Skov, P; Nissen, N I

    1997-06-01

    Recombinant human Interleukin-3 (RhIL-3) is a haemopoietic growth factor with effect both on early and differentiated cells, such as eosinophils and basophils, and it also acts as a histamine-releasing agent. The purpose of the present study was to examine whether in vivo rhIL-3 administration after chemotherapy affected basophil histamine levels and whether a concordance between rhIL-3 induced histamine release and side effects during the treatment could be demonstrated. Thirty patients with non-Hodgkin's lymphoma entered the study. All patients received 6 courses of chemotherapy, rhIL-3 was administered subcutaneously once daily after the second and the fourth course of chemotherapy from cycle day 2-15 at the dose levels 0.5, 1.0, 5.0, 7.5 and 10 micrograms/kg with 6 patients at each dose level. In cycle 6 recombinant human Granulocyte-Macrophage Colony-Stimulating Factor (rhGM-CSF) (3.0 micrograms/kg) was administered sequential/concurrent day 9-15 to rhIL-3 (day 2-15) at all dose levels except 7.5 micrograms/kg, where rhIL-3 was given day 2-8 and rhGM-CSF sequential day 9-15. Cycles 1, 3 and 5 served as control cycles with no cytokine therapy. During rhIL-3 treatment, and after CHOP chemotherapy, the basophil counts increased moderately especially during the recovery period day 15-22, and mainly at the two highest dose levels 7.5 and 10 micrograms/kg, but never exceeded the normal upper limit. Histamine levels in basophils were the same in patients before chemotherapy and healthy volunteers, and except from a trend to increased histamine level at 10 micrograms/kg on day 15, no difference was noted between rhIL-3 cycles and control cycles. Within 3-4 hr after rhIL-3 administration, a drop in histamine level in basophils was noted, which could be due to histamine-releasing properties of rhIL-3 as previously demonstrated by in vitro studies. No serious side effects were noted during the cytokine treatment, and despite that most patients had mild flushing of the

  1. [Effects of sulfur plus resin-coated controlled release urea fertilizer on winter wheat dry matter accumulation and allocation and grain yield].

    Science.gov (United States)

    Man, Jian-Guo; Zhou, Jie; Wang, Dong; Yu, Zhen-Wen; Zhang, Min; Hu, Zhi-Ying; Hou, Xiu-Tao

    2011-05-01

    A field experiment was conducted to study the effects of sulfur plus resin-coated urea fertilizer on the winter wheat dry matter accumulation and allocation and grain yield. Four treatments were installed, i.e., sulfur plus resin-coated urea (SRCU), resin-coated urea (RCU), sulfur-amended conventional urea (SU), and conventional urea (U). The coated urea fertilizers were applied as basal, and the conventional urea fertilizers were 50% applied as basal and 50% applied as topdressing. There were no significant differences in the plant dry matter accumulation and grain yield between treatments RCU and U. Under the conditions the available S content in 0-20 cm soil layer was 43.2 mg x kg(-1) and the S application rate was 91.4 kg x hm(-2), treatments SRCU and SU had no significant differences in the dry matter accumulation and allocation after anthesis and the grain yield, but the amount of the assimilates after anthesis allocated in grain, the grain-filling rate at mid grain-filling stage, the 1000-grain weight, and the grain yield in the two treatments were significantly higher than those in treatment RCU. When the available S content in 0-20 cm soil layer was 105.1 mg x kg(-1) and the S application rate was 120 kg x hm(-2), the grain yield in treatment SRCU was significantly higher than that in treatment SU, but had no significant difference with that in treatments RCU and U. These results suggested that from the viewpoints of dry matter accumulation and allocation and grain yield, the nitrogen released from SRCU had the same regulation effect as the conventional urea 50% applied as basal and 50% applied as topdressing, while the regulation effect of the sulfur released from SRCU was controlled by the available S content in 0-20 cm soil layer. When the soil available S content was 43.2 mg x kg(-1), the released sulfur could promote the dry matter accumulation after anthesis and the grain-filling, and increase the grain yield significantly; when the soil available S

  2. Plasma Histamine And Serotonin Levels In Children With Nephrotic Syndrome And Acute Poststreptococcal Glomerulonephritis

    Directory of Open Access Journals (Sweden)

    Nagwa Mohamed and Talaat El sayed

    2005-12-01

    Full Text Available Plasma histamine and serotonin concentrations were measured using fluorimeteric assay in 40 children with renal diseases. Minimal change nephrotic syndrome (15 focal segmental glomerulosclerosis(10 and acute poststreptococcal glomerulonephritis(15 to determine the relation between plasma levels of histamine and serotonin and these various types of renal diseases in children. Plasma histamine level was significantly increased in group of children with acute poststreptococcal glomerulonephritis. Plasma serotonin levels were significantly increased in all 3 groups of patient, when compared with those of controls. Raised plasma histamine in acute poststreptococcal glomerulonephritis group may be evidence of the acute immunological inflammation and defective renal excretion due to mild renal impairment in these children. Raised plasma serotonin in all 3 groups of patients may be due to diminished uptake and release of serotonin from platelets in children with minimal change nephrotic syndrome and focal segmental glomerulosclerosis and due to defective renal execretion in children with acute poststreptococcal glomerulo-nephritis.

  3. Target-specific near-IR induced drug release and photothermal therapy with accumulated Au/Ag hollow nanoshells on pulmonary cancer cell membranes.

    Science.gov (United States)

    Noh, Mi Suk; Lee, Somin; Kang, Homan; Yang, Jin-Kyoung; Lee, Hyunmi; Hwang, Doyk; Lee, Jong Woo; Jeong, Sinyoung; Jang, Yoonjeong; Jun, Bong-Hyun; Jeong, Dae Hong; Kim, Seong Keun; Lee, Yoon-Sik; Cho, Myung-Haing

    2015-03-01

    Au/Ag hollow nanoshells (AuHNSs) were developed as multifunctional therapeutic agents for effective, targeted, photothermally induced drug delivery under near-infrared (NIR) light. AuHNSs were synthesized by galvanic replacement reaction. We further conjugated antibodies against the epidermal growth factor receptor (EGFR) to the PEGylated AuHNS, followed by loading with the antitumor drug doxorubicin (AuHNS-EGFR-DOX) for lung cancer treatment. AuHNSs showed similar photothermal efficiency to gold nanorods under optimized NIR laser power. The targeting of AuHNS-EGFR-DOX was confirmed by light-scattering images of A549 cells, and doxorubicin release from the AuHNSs was evaluated under low pH and NIR-irradiated conditions. Multifunctional AuHNS-EGFR-DOX induced photothermal ablation of the targeted lung cancer cells and rapid doxorubicin release following irradiation with NIR laser. Furthermore, we evaluated the effectiveness of AuHNS-EGFR-DOX drug delivery by comparing two drug delivery methods: receptor-mediated endocytosis and cell-surface targeting. Accumulation of the AuHNS-EGFR-DOX on the cell surfaces by targeting EGFR turned out to be more effective for lung cancer treatments than uptake of AuHNS-EGFR-DOX. Taken together, our data suggest a new and optimal method of NIR-induced drug release via the accumulation of targeted AuHNS-EGFR-DOX on cancer cell membranes.

  4. Anaerobic fermentation combined with low-temperature thermal pretreatment for phosphorus-accumulating granular sludge: Release of carbon source and phosphorus as well as hydrogen production potential.

    Science.gov (United States)

    Zou, Jinte; Li, Yongmei

    2016-10-01

    Releases of organic compounds and phosphorus from phosphorus-accumulating granular sludge (PGS) and phosphorus-accumulating flocculent sludge (PFS) during low-temperature thermal pretreatment and anaerobic fermentation were investigated. Meanwhile, biogas production potential and microbial community structures were explored. The results indicate that much more soluble chemical oxygen demand (SCOD) and phosphorus were released from PGS than from PFS via low-temperature thermal pretreatment because of the higher extracellular polymeric substances (EPS) content in PGS and higher ratio of phosphorus reserved in EPS. Furthermore, PGS contains more anaerobes and dead cells, resulting in much higher SCOD and volatile fatty acids release from PGS than those from PFS during fermentation. PGS fermentation facilitated the n-butyric acid production, and PGS exhibited the hydrogen production potential during fermentation due to the presence of hydrogen-producing bacteria. Therefore, anaerobic fermentation combined with low-temperature thermal pretreatment can facilitate the recovery of carbon and phosphorus as well as producing hydrogen from PGS.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Time course of the effects of histamine, thioperamide and EEDQ on H3 receptors in the mouse brain.

    Science.gov (United States)

    Detzner, M; Kathmann, M; Schlicker, E

    1994-06-01

    The effects of histamine, thioperamide and EEDQ (N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline) at the noradrenaline release-modulating H3 receptor in the mouse brain were examined. In superfused mouse brain cortex slices preincubated with 3H-noradrenaline, the inhibitory effect of histamine on the electrically (0.3 Hz) evoked tritium overflow was virtually identical when the time of exposure was 30, 80 or 130 min; after withdrawal of histamine, the evoked overflow recovered within 80 min. The attenuation of the effect of histamine by thioperamide was reversible within 50 min after withdrawal of the antagonist, whereas the attenuation produced by EEDQ remained constant for at least 80 min. In conclusion, the effects of histamine and thioperamide at the H3 receptor are readily reversible, whereas EEDQ appears to be an irreversible antagonist; desensitization of the H3 receptor does not occur.

  8. Histamine-1 receptor blockade does not prevent nitroglycerin induced migraine. Support for the NO-hypothesis of migraine

    DEFF Research Database (Denmark)

    Lassen, L H; Thomsen, L L; Kruuse, C;

    1996-01-01

    It has previously been shown that in migraine sufferers infusion of glyceryl trinitrate (GTN) and histamine causes an immediate headache during the infusion and a genuine migraine attack one to several hours after the infusion. This identical time profile indicates a common mechanism of action....... To evaluate whether GTN causes headache via liberation of histamine, we studied the effect of GTN 0.5 micrograms.kg-1.min-1 for 20 min in seven migraine sufferers, once after pretreatment with the histamine-1 (H1)-receptor blocker mepyramine (0.5 mg.kg-1) and once without pretreatment. This mepyramine dose...... with transcranial Doppler, were also unaffected by the mepyramine pretreatment. Our results demonstrate that neither headache nor arterial dilatation due to GTN infusion is caused by histamine release. In all likelihood the common mediator of migraine induction by GTN and histamine is nitric oxide....

  9. 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.

  10. Pharmacological Evidence that Histamine H3 Receptors Mediate Histamine-Induced Inhibition of the Vagal Bradycardic Out-flow in Pithed Rats.

    Science.gov (United States)

    García, Mónica; García-Pedraza, José Ángel; Villalón, Carlos M; Morán, Asunción

    2016-02-01

    In vivo stimulation of cardiac vagal neurons induces bradycardia by acetylcholine (ACh) release. As vagal release of ACh may be modulated by autoreceptors (muscarinic M2 ) and heteroreceptors (including serotonin 5-HT1 ), this study has analysed the pharmacological profile of the receptors involved in histamine-induced inhibition of the vagal bradycardic out-flow in pithed rats. For this purpose, 180 male Wistar rats were pithed, artificially ventilated and pre-treated (i.v.) with 1 mg/kg atenolol, followed by i.v. administration of physiological saline (1 ml/kg), histamine (10, 50, 100 and 200 μg/kg) or the selective histamine H1 (2-pyridylethylamine), H2 (dimaprit), H3 (methimepip) and H4 (VUF 8430) receptor agonists (1, 10, 50 and 100 μg/kg each). Under these conditions, electrical stimulation (3, 6 and 9 Hz; 15 ± 3 V and 1 ms) of the vagus nerve resulted in frequency-dependent bradycardic responses, which were (i) unchanged during the infusions of saline, 2-pyridylethylamine, dimaprit or VUF 8430; and (ii) dose-dependently inhibited by histamine or methimepip. Moreover, the inhibition of the bradycardia caused by 50 μg/kg of either histamine or methimepip (which failed to inhibit the bradycardic responses to i.v. bolus injections of acetylcholine; 1-10 μg/kg) was abolished by the H3 receptor antagonist JNJ 10181457 (1 mg/kg, i.v.). In conclusion, our results suggest that histamine-induced inhibition of the vagal bradycardic out-flow in pithed rats is mainly mediated by pre-junctional activation of histamine H3 receptors, as previously demonstrated for the vasopressor sympathetic out-flow and the vasodepressor sensory CGRPergic (calcitonin gene-related peptide) out-flow.

  11. 草药复方Bresol(R)抵抗化合物48/80诱导的肥大细胞脱颗粒及组胺释放:促使肥大细胞稳定的一种非免疫机制%Polyherbal formulation Bresol(R) protects the mast cells against compound 48/80-induced disruption and histamine release: a non-immunological mechanism of mast cell stabilization

    Institute of Scientific and Technical Information of China (English)

    Yathiraj Ashwini; Mohamed Rafiq; Gollapalle L. Viswanatha; Subbanna Raiesh; Selvam Senthilraja; Mohammed Azeemuddin; Suryakanth D.Anturlikar; Paramesh Rangesh; Pralhad S.Patki

    2012-01-01

    OBJECTIVE:Present study was aimed to evaluate the protective effect of Bresol(R),a polyherbal formulation,on mast cell degranulation and histamine release from mast cells.METHODS:Mast cell-stabilizing activity of Bresol~was evaluated against compound 48/80-induced mast cell degranulation and histamine release from rat peritoneal mast cells in ex vivo conditions.RESULTS:Microscopy of the control group smears showed more of intact mast cells,with very minimum number of degranulated mast cells and negligible amount of histamine release.In contrast,incubation of mast cells with compound 48/80 caused significant degranulation of the mast cells associated with release of high concentration of histamine in the positive control group.Furthermore,Bresol(R) at 100 mg/L showed a significant inhibition of compound 48/80-induced mast cell degranulation.In addition,Bresol(R) significantly and dose-dependently inhibited compound 48/80-induced histamine release.CONCLUSION:Bresol(R) inhibits compound 48/80-induced mast cell degranulation and histamine release in ex vivo conditions.The present findings could be one of the non-immunological mechanism responsible for usefulness of Bresol(R) in various allergic conditions.%目的:研究一种草药复方制剂Bresol(R)对于肥大细胞脱颗粒以及组胺释放的保护作用.方法:使用大鼠腹膜内肥大细胞,在体外经化合物48/80诱导肥大细胞脱颗粒及组胺释放,评估Bresol(R)稳定肥大细胞的作用.结果:显微镜下正常对照组涂片显示较多完整的肥大细胞,有极少量的脱颗粒肥大细胞和微量的组胺释放.阳性对照组中用化合物48/80培养的肥大细胞出现了显著的肥大细胞脱颗粒现象以及高浓度的组胺释放.而100 mg/L浓度的Bresol(R)明显抑制了化合物48/80诱导的肥大细胞脱颗粒.此外,Bresol(R)可有效抑制化合物48/80诱导的组胺释放,且抑制效果与剂量有关.结论:Bresol(R)能够在体外抑制化合物48/80

  12. Effects of multivalent histamine supported on gold nanoparticles: activation of histamine receptors by derivatized histamine at subnanomolar concentrations.

    Science.gov (United States)

    Gasiorek, Friederike; Pouokam, Ervice; Diener, Martin; Schlecht, Sabine; Wickleder, Mathias S

    2015-10-21

    Colloidal gold nanoparticles with a functionalized ligand shell were synthesized and used as new histamine receptor agonists. Mercaptoundecanoic acid moieties were attached to the surface of the nanoparticles and derivatized with native histamine. The multivalent presentation of the immobilized ligands carried by the gold nanoparticles resulted in extremely low activation concentrations for histamine receptors on rat colonic epithelium. As a functional read-out system, chloride secretion resulting from stimulation of neuronal and epithelial histamine H1 and H2 receptors was measured in Ussing chamber experiments. These responses were strictly attributed to the histamine entities as histamine-free particles Au-MUDOLS or the monovalent ligand AcS-MUDA-HA proved to be ineffective. The vitality of the tissues used was not impaired by the nanoparticles.

  13. Vasopeptidase-activated latent ligands of the histamine receptor-1.

    Science.gov (United States)

    Gera, Lajos; Roy, Caroline; Charest-Morin, Xavier; Marceau, François

    2013-11-01

    Whether peptidases present in vascular cells can activate prodrugs active on vascular cells has been tested with 2 potential latent ligands of the histamine H1 receptor (H1R). First, a peptide consisting of the antihistamine cetirizine (CTZ) condensed at the N-terminus of ε-aminocaproyl-bradykinin (εACA-BK) was evaluated for an antihistamine activity that could be revealed by degradation of the peptide part of the molecule. CTZ-εACA-BK had a submicromolar affinity for the BK B2 receptor (B2R; IC50 of 590 nM, [(3)H]BK binding competition), but a non-negligible affinity for the human H1 receptor (H1R; IC50 of 11 μM for [(3)H]pyrilamine binding). In the human isolated umbilical vein, a system where both endogenous B2R and H1R mediate strong contractions, CTZ-εACA-BK exerted mild antagonist effects on histamine-induced contraction that were not modified by omapatrilat or by a B2R antagonist that prevents endocytosis of the BK conjugate. Cells expressing recombinant ACE or B2R incubated with CTZ-εACA-BK did not release a competitor of [(3)H]pyrilamine binding to H1Rs. Thus, there is no evidence that CTZ-εACA-BK can release free cetirizine in biological environments. The second prodrug was a blocked agonist, L-alanyl-histamine, potentially activated by aminopeptidase N (APN). This compound did not compete for [(3)H]pyrilamine binding to H1Rs. The human umbilical vein contractility assay responded to L-alanyl-histamine (EC50 54.7 μM), but the APN inhibitor amastatin massively (17-fold) reduced its apparent potency. Amastatin did not influence the potency of histamine as a contractile agent. One of the 2 tested latent H1R ligands, L-alanyl-histamine, supported the feasibility of pro-drug activation by vascular ectopeptidases.

  14. Histamine-producing Lactobacillus parabuchneri strains isolated from grated cheese can form biofilms on stainless steel.

    Science.gov (United States)

    Diaz, Maria; Del Rio, Beatriz; Sanchez-Llana, Esther; Ladero, Victor; Redruello, Begoña; Fernández, María; Martin, M Cruz; Alvarez, Miguel A

    2016-10-01

    The consumption of food containing large amounts of histamine can lead to histamine poisoning. Cheese is one of the most frequently involved foods. Histamine, one of the biogenic amines (BAs) exhibiting the highest safety risk, accumulates in food contaminated by microorganisms with histidine decarboxylase activity. The origin of these microorganisms may be very diverse with contamination likely occurring during post-ripening processing, but the microorganisms involved during this manufacturing step have never been identified. The present work reports the isolation of 21 histamine-producing Lactobacillus parabuchneri strains from a histamine-containing grated cheese. PCR revealed that every isolate carried the histidine decarboxylase gene (hdcA). Eight lineages were identified based on the results of genome PFGE restriction analysis plus endonuclease restriction profile analysis of the carried plasmids. Members of all lineages were able to form biofilms on polystyrene and stainless steel surfaces. L. parabuchneri is therefore an undesirable species in the dairy industry; the biofilms it can produce on food processing equipment represent a reservoir of histamine-producing bacteria and thus a source of contamination of post-ripening-processed cheeses.

  15. Tyramine and histamine risk assessment related to consumption of dry fermented sausages by the Spanish population.

    Science.gov (United States)

    Latorre-Moratalla, M L; Comas-Basté, O; Bover-Cid, S; Vidal-Carou, M C

    2017-01-01

    Tyramine and histamine are the main dietary bioactive amines related to acute adverse health effects. Dry fermented sausages can easily accumulate high levels of these hazards and are frequently consumed in Spain. The present work aims to assess the exposure to tyramine and histamine from the consumption of dry fermented sausages by the Spanish population and to assess the risk to suffer acute health effects from this exposure. A probabilistic estimation of the exposure to these hazards was derived combining probability distributions of these amines in dry fermented sausages (n = 474) and their consumption by the Spanish population. The mean dietary exposure to tyramine and histamine was 6.2 and 1.39 mg/meal, respectively. The risk of suffering hypertensive crisis or histamine intoxication by healthy population due to tyramine or histamine intake, respectively, exclusively from dry fermented sausages, can be considered negligible. For individuals under treatment with MAOI drugs, the probability to surpass the safe threshold dose (6 mg/meal) was estimated as 34%. For patients with histamine intolerance, even the presence of this amine in food is not tolerable and it could be estimated that 7000 individuals per million could be at risk to suffer the related symptoms after consuming dry fermented sausages.

  16. The other side of the histamine H3 receptor.

    Science.gov (United States)

    Ellenbroek, Bart A; Ghiabi, Bibinaz

    2014-04-01

    Although histamine H3 receptors are predominantly known as presynaptic receptors, regulating the release of neurotransmitters such as dopamine, acetylcholine, and histamine, in the striatal complex the vast majority of these receptors are actually located on the other side, in other words postsynaptically. Given their strategic location, they can crucially affect signaling throughout the basal ganglia. We describe the anatomy and function of H3 receptors within the basal ganglia with a specific focus on their colocalization with dopamine D1 and D2 receptors. Because the basal ganglia are centrally involved in several major neurological and psychiatric disorders, we also discuss the therapeutic potential of drugs targeting H3 receptors in the treatment of Parkinson disease (PD), schizophrenia, and addiction.

  17. The Effects of Controlled Release Fertilizer and Conventional Complex Fertilizer on the Dry Matter Accumulation and the Yield in Winter Wheat

    Directory of Open Access Journals (Sweden)

    Guoqing Li

    2013-03-01

    Full Text Available In order to research the use ratio of controlled release fertilizer in winter wheat. So, the experiment about the effects of Controlled Release Fertilizer (CRF and Conventional Complex Fertilizer (CCF on the dry matter accumulation and the grain yield in winter wheat has studied with pots in the open field. The results indicated that the CRF improved the proportion of the number of effective tillers to the total number of tillers. And the mixture of the CRF and equivalent CCF have more improved the proportion of the dry root weight to the total dry matters of the after of wheat flowering stage than that of the CRF used alone (T1, T2, T3. The treatment T6 was more improved the accumulation of the dry matters of aerial part than others. And the weight gain of T6 after a thesis was higher than other treatments and the control treatment (CK. In the facts of grain number per spike, thousand grain weight and yield, the treatments of the mixture of the CRF and equivalent CCF (T4,T5,T6 were higher than that of the treatments of CRF used only (T1,T2,T3 and CK, in which the T6 was highest. So, we think that this treatment namely T6 was used fertilizers least and gained the highest yield of grain.

  18. 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...... diet affected the amount of urinary metabolites. Fifteen healthy subjects were challenged four times with 100 mg of histamine. Results were monitored by the urinary recovery of 1,4-methylimidazole acetic acid (MIAA) from 24 h before to 72 h after challenge. Urine was collected in 24-h samples except...... 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...

  19. Effect of central and peripheral actions of histamine and its metabolite N-alpha methyl histamine on gastric secretion and acute gastric lesions.

    Science.gov (United States)

    Kwiecień, S; Brzozowski, T; Konturek, P C; Konturek, S J; Pawlik, M; Pajdo, R; Drozdowicz, D; Ptak, A; Hahn, E G

    2001-12-01

    N alpha-methylhistamine (N alpha-MH) is one of unusual metabolite of histamine that was found in Helicobacter pylori-infected stomach and is believed to interact with specific histamine H1, H2 and H3-receptors to stimulate gastric acid secretion and gastrin release from isolated G-cells but the effects of N alpha-MH on gastric mucosal integrity have been little studied. This study was designed; 1) to compare the effect of intraperitoneal (i.p.), intracerebroventricular (i.c.v.) and gastric topical (intragastric i.g.) application of exogenous N alpha-MH with that of standard histamine on gastric secretion in rats equipped with gastric fistula (series A) and 2) to compare the effect of i.c.v. administration of histamine and N alpha-MH with that of peripheral (i.p. and i.g.) application of these amines on gastric lesions induced by 100% ethanol (series B) in rats with or without capsaicin-induced deactivation of sensory nerves. The area of gastric lesions was determined planimetrically, gastric blood flow (GBF) was assessed by H2-gas clearance method and venous blood was collected for determination of plasma gastrin levels by RIA. N alpha-MH and histamine (0.1-10 mg/kg i.p. or i.g.) dose-dependently increased gastric acid output (series A); whereas i.c.v. administration of histamine or N alpha-MH inhibited dose-dependently this secretion; the dose attenuating gastric acid output by 50% (ED50) being 4 and 6 microg/kg i.c.v. Both, N alpha-MH and histamine (2 mg/kg i.p. and i.g.) attenuated significantly the area of gastric lesions induced by 100% ethanol (series B) while producing significant rise in the GBF and plasma immunoreactive gastrin increments. Central application of N alpha-MH and histamine (0.01-5 microg/kg i.c.v.) inhibited ethanol-induced gastric damage whereas higher doses ranging from 10-100 microg/kg of histamine and N alpha-MH were significantly less effective. Capsaicin-induced deactivation of sensory nerves by itself augmented significantly ethanol

  20. Histamine Recycling Is Mediated by CarT, a Carcinine Transporter in Drosophila Photoreceptors.

    Science.gov (United States)

    Xu, Ying; An, Futing; Borycz, Jolanta A; Borycz, Janusz; Meinertzhagen, Ian A; Wang, Tao

    2015-12-01

    Histamine is an important chemical messenger that regulates multiple physiological processes in both vertebrate and invertebrate animals. Even so, how glial cells and neurons recycle histamine remains to be elucidated. Drosophila photoreceptor neurons use histamine as a neurotransmitter, and the released histamine is recycled through neighboring glia, where it is conjugated to β-alanine to form carcinine. However, how carcinine is then returned to the photoreceptor remains unclear. In an mRNA-seq screen for photoreceptor cell-enriched transporters, we identified CG9317, an SLC22 transporter family protein, and named it CarT (Carcinine Transporter). S2 cells that express CarT are able to take up carcinine in vitro. In the compound eye, CarT is exclusively localized to photoreceptor terminals. Null mutations of cart alter the content of histamine and its metabolites. Moreover, null cart mutants are defective in photoreceptor synaptic transmission and lack phototaxis. These findings reveal that CarT is required for histamine recycling at histaminergic photoreceptors and provide evidence for a CarT-dependent neurotransmitter trafficking pathway between glial cells and photoreceptor terminals.

  1. Prejunctional inhibition of sympathetically evoked pupillary dilation in cats by activation of histamine H3 receptors.

    Science.gov (United States)

    Koss, M C; Hey, J A

    1993-08-01

    Frequency-dependent pupillary dilations were evoked by electrical stimulation of the pre- or post-ganglionic cervical sympathetic nerve (sympatho-excitation) or the hypothalamus (parasympatho-inhibition) in sympathectomized anesthetized cats. Systemic administration of the selective histamine H3 receptor agonist (R)-alpha-methylhistamine (R alpha MeHA) produced a dose-dependent depression of mydriasis due to direct neural sympathetic activation but had no effect on responses elicited by parasympathetic withdrawal. The histamine H2 receptor agonist, dimaprit, was inactive. R alpha MeHA was much more effective in depressing sympathetic responses obtained at lower frequencies when compared to higher frequencies of stimulation. Responses evoked both pre- and postganglionically were inhibited by R alpha MeHA. This peripheral sympatho-inhibitory action of R alpha MeHA was antagonized by the histamine H3 receptor blocker thioperamide but not by intravenous pretreatment with the histamine H1 receptor antagonist chlorpheniramine. Histamine H2 receptor blockers cimetidine and ranitidine were also without effect. R alpha MeHA did not depress pupillary responses elicited by i.v. (-)-adrenaline. The results demonstrate that histamine H3 receptors modulate sympathetic activation of the iris at a site proximal to the iris dilator muscle. The predominant mechanism of action appears to the prejunctional inhibition of noradrenaline release from postganglionic sympathetic nerve endings. However, a concomitant ganglionic inhibitory action cannot be excluded.

  2. Histamine and betahistine in the treatment of vertigo: elucidation of mechanisms of action.

    Science.gov (United States)

    Lacour, M; Sterkers, O

    2001-01-01

    The aim of this review is to provide clinicians with a picture of the mechanisms by which: histamine and histaminergic agonists act on the vestibular system both peripherally and centrally; and histaminergic agonists and antagonists interfere with the recovery process after peripheral vestibular lesion. We have focused on betahistine, a structural analogue of histamine with weak histamine H(1) receptor agonist and more potent H(3) receptor antagonist properties, to review the currently available data on the role of the histaminergic system in the recovery process after peripheral vestibular deficits and the effects of histamine analogues in the clinical treatment of vertigo. This review provides new insights into the basic mechanisms by which betahistine improves vestibular compensation in animal models of unilateral vestibular dysfunction, and elucidates particularly the mechanisms of action of this substance at the level of the CNS. It is proposed that betahistine may reduce peripherally the asymmetric functioning of the sensory vestibular organs in addition to increasing vestibulocochlear blood flow by antagonising local H(3) heteroreceptors. Betahistine acts centrally by enhancing histamine synthesis within tuberomammillary nuclei of the posterior hypothalamus and histamine release within vestibular nuclei through antagonism of H(3) autoreceptors. This mechanism, together with less specific effects of betahistine on alertness regulation through cerebral H(1) receptors, should promote and facilitate central vestibular compensation. Elucidation of the mechanisms of action of betahistine is of particular interest for the treatment of vestibular and cochlear disorders and vertigo.

  3. Cystine accumulation attenuates insulin release from the pancreatic β-cell due to elevated oxidative stress and decreased ATP levels.

    Science.gov (United States)

    McEvoy, Bernadette; Sumayao, Rodolfo; Slattery, Craig; McMorrow, Tara; Newsholme, Philip

    2015-12-01

    The pancreatic β-cell has reduced antioxidant defences making it more susceptible to oxidative stress. In cystinosis, a lysosomal storage disorder, an altered redox state may contribute to cellular dysfunction. This rare disease is caused by an abnormal lysosomal cystine transporter, cystinosin, which causes excessive accumulation of cystine in the lysosome. Cystinosis associated kidney damage and dysfunction leads to the Fanconi syndrome and ultimately end-stage renal disease. Following kidney transplant, cystine accumulation in other organs including the pancreas leads to multi-organ dysfunction. In this study, a Ctns gene knockdown model of cystinosis was developed in the BRIN-BD11 rat clonal pancreatic β-cell line using Ctns-targeting siRNA. Additionally there was reduced cystinosin expression, while cell cystine levels were similarly elevated to the cystinotic state. Decreased levels of chronic (24 h) and acute (20 min) nutrient-stimulated insulin secretion were observed. This decrease may be due to depressed ATP generation particularly from glycolysis. Increased ATP production and the ATP/ADP ratio are essential for insulin secretion. Oxidised glutathione levels were augmented, resulting in a lower [glutathione/oxidised glutathione] redox potential. Additionally, the mitochondrial membrane potential was reduced, apoptosis levels were elevated, as were markers of oxidative stress, including reactive oxygen species, superoxide and hydrogen peroxide. Furthermore, the basal and activated phosphorylated forms of the redox-sensitive transcription factor NF-κB were increased in cells with silenced Ctns. From this study, the cystinotic-like pancreatic β-cell model demonstrated that the altered oxidative status of the cell, resulted in depressed mitochondrial function and pathways of ATP production, causing reduced nutrient-stimulated insulin secretion.

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

    OpenAIRE

    Mahmood, Danish

    2016-01-01

    Histamine H3 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. H3 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, bex...

  5. Mast cell-derived histamine mediates cystitis pain.

    Directory of Open Access Journals (Sweden)

    Charles N Rudick

    Full Text Available BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Cesium accumulation by aquatic organisms at different trophic levels following an experimental release into a small reservoir

    Energy Technology Data Exchange (ETDEWEB)

    Pinder, J.E., E-mail: jepinder@uga.ed [Savannah River Ecology Laboratory, P. O. Drawer E, Aiken, SC 29802 (United States); Hinton, T.G., E-mail: thomas.hinton@irsn.f [Savannah River Ecology Laboratory, P. O. Drawer E, Aiken, SC 29802 (United States); Taylor, B.E., E-mail: TaylorB@dnr.sc.go [Savannah River Ecology Laboratory, P. O. Drawer E, Aiken, SC 29802 (United States); Whicker, F.W., E-mail: ward.whicker@colostate.ed [Department of Environmental and Radiological Health Sciences, Colorado, State University, Fort Collins, CO 80523-1618 (United States)

    2011-03-15

    The rates of accumulation and subsequent loss of stable cesium ({sup 133}Cs) by organisms at different trophic levels within plankton-based and periphyton-based food chains were measured following the addition of {sup 133}Cs into a small reservoir near Aiken, South Carolina, USA. An uptake parameter u (L kg{sup -1} d{sup -1} dry mass) and a loss rate parameter k (d{sup -1}) were estimated for each organism using time-series measurements of {sup 133}Cs concentrations in water and biota, and these parameters were used to estimate maximum concentrations, times to maximum concentrations, and concentration ratios (C{sub r}). The maximum {sup 133}Cs concentrations for plankton, periphyton, the insect larva Chaoborus punctipennis, which feeds on plankton, and the snail Helisoma trivolvis, which feeds on periphyton, occurred within the first 14 days following the addition, whereas the maximum concentrations for the fish species Lepomis macrochirus and Micropterus salmoides occurred after 170 days. The C{sub r} based on dry mass for plankton and C. punctipennis were 1220 L kg{sup -1} and 5570 L kg{sup -1}, respectively, and were less than the C{sub r} of 8630 L kg{sup -1} for periphyton and 47,700 L kg{sup -1} for H. trivolvis. Although the C{sub r} differed between plankton-based and periphyton-based food chains, they displayed similar levels of biomagnification. Biomagnification was also indicated for fish where the C{sub r} for the mostly nonpiscivorous L. macrochirus of 22,600 L kg{sup -1} was three times less than that for mostly piscivorous M. salmoides of 71,500 L kg{sup -1}. Although the C{sub r} for M. salmoides was greater than those for periphyton and H. trivolvis, the maximum {sup 133}Cs concentrations for periphyton and H. trivolvis were greater than that for M. salmoides. - Research highlights: {yields} A simple uptake and loss model described the Cs dynamics in all the various biota. {yields} Concentrations of Cs were greater in periphyton than in plankton

  8. 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....... In the present article we review current evidence pointing at an important role of histamine in the regulation of appetite and metabolism. Studies using both knockout mouse models as well as pharmacological studies have revealed that histamine acts as an anorexigenic agent via stimulation of histamine H(1......) receptors. One effect of histamine in the regulation of appetite is to act as a mediator of the inhibitory effect of leptin on appetite. It seems that histamine may attenuate and delay the development of leptin resistance in high-fat-diet-induced obesity. Furthermore, histamine may also act to accelerate...

  9. Estimation of recurrence interval of large earthquakes on the central Longmen Shan fault zone based on seismic moment accumulation/release model.

    Science.gov (United States)

    Ren, Junjie; Zhang, Shimin

    2013-01-01

    Recurrence interval of large earthquake on an active fault zone is an important parameter in assessing seismic hazard. The 2008 Wenchuan earthquake (Mw 7.9) occurred on the central Longmen Shan fault zone and ruptured the Yingxiu-Beichuan fault (YBF) and the Guanxian-Jiangyou fault (GJF). However, there is a considerable discrepancy among recurrence intervals of large earthquake in preseismic and postseismic estimates based on slip rate and paleoseismologic results. Post-seismic trenches showed that the central Longmen Shan fault zone probably undertakes an event similar to the 2008 quake, suggesting a characteristic earthquake model. In this paper, we use the published seismogenic model of the 2008 earthquake based on Global Positioning System (GPS) and Interferometric Synthetic Aperture Radar (InSAR) data and construct a characteristic seismic moment accumulation/release model to estimate recurrence interval of large earthquakes on the central Longmen Shan fault zone. Our results show that the seismogenic zone accommodates a moment rate of (2.7 ± 0.3) × 10¹⁷ N m/yr, and a recurrence interval of 3900 ± 400 yrs is necessary for accumulation of strain energy equivalent to the 2008 earthquake. This study provides a preferred interval estimation of large earthquakes for seismic hazard analysis in the Longmen Shan region.

  10. [Histamine liberation and specific IgE against Dermatophagoides pteronyssinus in parasitized patients].

    Science.gov (United States)

    Moneo, I; Puente, S; Subirats, M; Ruiz, A; Lozano, M; González-Muñoz, M

    1994-01-01

    We studied 98 patients with different parasitosis, without clinical symptoms of mite sensitization, most of them coming from Guinea. Histamine release to Dermatophagoides pteronyssinus was performed using whole blood. Specific IgE to the same antigen was measured by EAST, as well as by an immunodot with the same antigen extract employed for the histamine release test. Finally, the EAST positive sera were studied by immunoblotting. The presence of specific IgE by EAST could be proved in 31 patients, but these antibodies were nor detected by dot, blot and histamine release. On the other hand, only two patients showed a positive histamine release test to D. pteronyssinus and in these two cases the EAST to mites was negative. There was no relation between total IgE levels and specific IgE to mites. The presence of mite-specific IgE showed a significative association to the parasite Trichuris trichiura (odds ratio 3.09). This fact suggest that the specific IgE values found in this population can reflect some cross-reaction between parasites and allergens. It is the author's opinion that the same study should be performed in european patients in order to test the relationship between mite-specific antibodies and the presence of parasites, specially of Trichuris trichiura.

  11. Histamine H3-receptor isoforms.

    Science.gov (United States)

    Bakker, R A

    2004-10-01

    Increasing evidence supports a role for HA as a neurotransmitter and neuromodulator in various brain functions, including emotion, cognition, and feeding. The recent cloning of the histamine H3 receptor allowed for the subsequent cloning of a variety of H3 receptor isoforms from different species as well as the H4 receptor. As a result a wide variety of H3-receptor isoforms are now known that display differential brain expression patterns and signalling properties. These recent discoveries are discussed in view of the growing interest of the H3 receptor as a target for the development of potential therapeutics.

  12. Histamine Formation in a Dry Salted Twaite Shad ( Alosa fallax lacustris ) Product.

    Science.gov (United States)

    Vasconi, Mauro; Bellagamba, Federica; Bernardi, Cristian; Martino, Piera Anna; Moretti, Vittorio Maria

    2017-01-01

    Landlocked shad is a freshwater clupeid fish ( Alosa fallax lacustris ) whose consumption is associated with the risk of scombrotoxin poisoning. Traditionally, fresh shad are subjected to an artisanal processing procedure, consisting of dry salting and maturation under pressure, to give a fish product named missoltino , which is stored in large metallic barrels and is sold to local consumers and restaurants. In recent years, the introduction of modern food packaging technologies has enabled this product to also be distributed in shops and supermarkets. Consequently, the determination of the safety of this product is an urgent issue. The aims of the present research were to measure histamine levels and histamine-forming bacteria in shad products collected at different phases of preparation and ripening, in order to minimize poison hazards, to provide technical information about risk, and to standardize the production process. One hundred twenty-six samples of shad (21 fresh fish and 105 dried) at different phases of preparation and ripening were collected from seven producers and were analyzed for chemical composition, histamine content, and microbiological properties. After 130 days of ripening, samples from three producers presented unacceptable amounts of histamine (>200 mg/kg), according to European Union legislation. A moderate negative correlation was found between histamine levels and salt content (r =-0.504, P shad at the end of ripening led to a drastic decrease of bacteria, but not of histamine. The most effective preventive measures for histamine formation and accumulation in salted shad were strictly related to fish handling and storage conditions during processing.

  13. DIETARY EFFECTS OF MAGNESIUM ON HISTAMINE METABOLISM AND URINE ACIDITY IN DOMESTIC FELINES

    Directory of Open Access Journals (Sweden)

    Sarah K. Martin

    2012-01-01

    Full Text Available Magnesium deficiency has been associated with increased histamine production in rats. Limitation of Mg with acidifying foods is common practice for management of urinary tract health in domestic cats. Nine healthy adult female shorthair cats were used in a 3 period random crossover experiment with fixed treatment sequences to test the effects of dietary Mg (0.06, 0.12 and 0.18% DM on histamine in blood and urine. The dry-extruded test foods were fed in sufficient amounts to maintain ideal body weight and obtain a target urine pH of 6.3. Each experimental period was preceded by a 7d wash out period, in which the 0.06% Mg food was fed, followed by a 14d feeding period of the appropriate food. Two 24 h total urine collections were performed (d13: Acidified, d14: Un-acidified; immediately iced and blood was collected on d14. Dry matter intake (p≥0.13 and BW (p≥0.13 were not affected by treatment. Plasma Mg concentration increased linearly with increasing dietary Mg (0.54, 0.56, 0.58 mM; p = 0.001. In contrast, plasma concentrations of threonine, histidine and tryptophan were lower in cats fed 0.12% Mg compare with 0.06 or 0.18% Mg (quadratic, p≤0.03. Urine output (p≥0.17, pH (p≥0.55, NH3 (p≥0.21 and titratable acidity of urine (p≥0.14 were similar across treatments. Urinary histamine excretion responded quadratically (p = 0.02 to treatment (3483, 3369, 3986 ng/d, whereas urinary histamine: Creatinine (p≥0.43 and plasma histamine concentration (p≥0.55 were unaffected. Differences were not detected among treatments in total histamine, cellular + noncellular histamine, (p≥0.11 or antigen-induced (p≥0.21 histamine release in whole blood. These data indicate that dietary Mg concentration, from 0.06-0.18%, does not affect urinary acidity or circulating histamine concentrations, however, supplying Mg at 0.18% may increase urinary histamine excretion.

  14. Brain histamine mediates the bombesin-induced central activation of sympatho-adrenomedullary outflow.

    Science.gov (United States)

    Okuma, Y; Yokotani, K; Murakami, Y; Osumi, Y

    1997-01-01

    Intracerebroventricular (i.c.v.) administration of bombesin (0.3 nmol) increased plasma levels of both adrenaline and noradrenaline in urethane anesthetized rats. These bombesin-induced increases were inhibited by i.c.v. pretreatment with pyrilamine, an H1-receptor antagonist. Ranitidine, an H2-receptor antagonist also inhibited the increase of adrenaline, however, its effective dose was much larger than that of pyrilamine. Furthermore, the bombesin-induced increase of noradrenaline was not effectively inhibited by ranitidine. In the next series, turnover of histamine was assessed by measuring accumulation of tele-methylhistamine (t-MH), a major metabolite of brain histamine. I.c.v. administration of bombesin (0.3-3 nmol) increased turnover of hypothalamic histamine, while its intravenous administration was without effect. The present results suggest that the bombesin-induced central activation of sympatho-adrenomedullary outflow is probably, at least in part, mediated through brain histaminergic neurons.

  15. Effects of sodium cromoglycate and nedocromil sodium on histamine secretion from human lung mast cells.

    Science.gov (United States)

    Leung, K B; Flint, K C; Brostoff, J; Hudspith, B N; Johnson, N M; Lau, H Y; Liu, W L; Pearce, F L

    1988-01-01

    Sodium cromoglycate and nedocromil sodium produced a dose dependent inhibition of histamine secretion from human pulmonary mast cells obtained by bronchoalveolar lavage and by enzymatic dissociation of lung parenchyma. Both compounds were significantly more active against the lavage cells than against the dispersed lung cells, and nedocromil sodium was an order of magnitude more effective than sodium cromoglycate against both cell types. Tachyphylaxis was observed with the parenchymal cells but not with the lavage cells. Nedocromil sodium and sodium cromoglycate also inhibited histamine release from the lavage cells of patients with sarcoidosis and extrinsic asthma. PMID:2462755

  16. 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…

  17. Histamine H3 receptors--general characterization and their function in the cardiovascular system.

    Science.gov (United States)

    Malinowska, B; Godlewski, G; Schlicker, E

    1998-06-01

    The histamine H3 receptor was initially identified as a presynaptic autoreceptor controlling histamine release and synthesis in the brain. It belongs to the superfamily of G protein-coupled receptors. The existence of the H3 receptor which has not yet been cloned was definitely established by the design of highly potent and selective agonists (R-(-)-alpha-methylhistamine, imetit) and antagonists (thioperamide, clobenpropit). These receptors also occur as heteroreceptors both in the central nervous system and on peripheral neurons of the gastrointestinal and bronchial tract, where they regulate the release of a variety of neurotransmitters. In the cardiovascular system, histamine H3 receptors are mainly located presynaptically on the postganglionic sympathetic nerve fibers innervating the blood vessels and the heart. Their activation leads to the inhibition of noradrenaline release and consequently to the reduction of the neurogenic vasopressor and cardiostimulatory responses. The presence of such receptors has been shown both in vitro (human, pig, guinea-pig, rabbit, rat isolated tissues) and in vivo (rat, guinea-pig). The vascular and cardiac presynaptic H3 receptors may be activated by endogenous histamine. The vascular H3 receptors appear to be operative in hypertension and interact with presynaptic alpha 2-adrenoceptors. Postsynaptic vasodilatatory H3 receptors have been detected in several vascular beds as well. H3 receptor ligands affect basal cardiovascular parameters in conscious and anesthetized guinea-pigs but not rats. Presynaptic H3 receptors may play a role in the pathophysiology of headache and cardiac ischemia.

  18. Inhibition by drugs of passive cutaneous anaphylaxis-induced skin histamine decrease.

    Directory of Open Access Journals (Sweden)

    Yokoyama,Hiroshi

    1984-08-01

    Full Text Available Passive cutaneous anaphylaxis (PCA was produced in the rat with mouse IgE-rich antiserum. The effect of drugs on the PCA-induced skin histamine decrease and leakage of protein-bound dye was studied. Salbutamol (0.5 mg/kg i.v. or 1.0 mg/kg s.c. and cromoglycate (10 mg/kg i.v. significantly inhibited the skin histamine decrease. A combination of salbutamol (0.5 mg/kg i.v. or 1.0 mg/kg s.c. and aminophylline (25 mg/kg i.v. or 75 mg/kg s.c. had an additive or greater than additive effect on the histamine decrease. Salbutamol (1.0 mg/kg s.c. inhibited the dye leakage markedly, and aminophylline (75 mg/kg s.c. slightly. These results indicate that the decrease in the skin histamine content is useful as an index of the in vivo inhibitory effect of antiallergic drugs on the antigen-induced histamine release.

  19. Synthesis of histamine by Haemophilus influenzae.

    Science.gov (United States)

    Sheinman, B D; Devalia, J L; Davies, R J; Crook, S J; Tabaqchali, S

    1986-03-29

    Recent findings suggest that bacteria might contribute to histamine concentrations in the sputum of patients with infective lung disease. Ten isolates of Haemophilus influenzae from patients with acute exacerbation of chronic bronchitis and emphysema, together with two reference strains, were incubated at 37 degrees C for 72 hours. Serial estimations of histamine concentrations by high pressure liquid chromatography showed significant increases at 24 and 48 hours; no increases were evident in the control samples. These findings suggest that H influenzae might contribute to inflammation and limited airflow in infective lung disease by producing histamine.

  20. Pharmacological investigation into the effects of histamine and histamine analogues on guinea-pig and rat colon in vitro.

    OpenAIRE

    Aguilar, M. J.; MORALES-OLIVAS, F. J.; RUBIO, E.

    1986-01-01

    The effects of histamine and specific histamine agonists has been examined on isolated longitudinal colon strips of guinea-pig and rat. Histamine and 2-pyridyl-ethylamine but not 4 methylhistamine produced a concentration-related contractile response in the guinea-pig colon. The H1-antagonist clemizole antagonized competitively the effect of histamine but the H2-antagonist ranitidine did not modify the dose-response curve to histamine in the guinea-pig colon. Atropine, hexamethonium, prazosin...

  1. Activation of mesolimbic dopaminergic neurons following central administration of histamine is mediated by H1 receptors.

    Science.gov (United States)

    Fleckenstein, A E; Lookingland, K J; Moore, K E

    1993-01-01

    The effect of intracerebroventricular administration of histamine on the activity of mesolimbic and nigrostriatal dopaminergic (DA) neurons was determined in male rats. The activity of these neurons was estimated by measuring: (1) the accumulation of 3,4-dihydroxyphenylalanine (DOPA) after administration of a decarboxylase inhibitor, and (2) the concentration of 3,4-dihydroxyphenylacetic acid (DOPAC) in the nucleus accumbens and striatum, which contain the terminals of these neurons. Central administration of histamine increased both DOPA accumulation and DOPAC concentrations in the nucleus accumbens, but was without effect in the striatum. The increase in DOPAC concentrations in the nucleus accumbens occurred within 10 min and was sustained for at least 120 min. The H1 antagonist mepyramine blocked whereas the H2 antagonist zolantidine did not affect histamine-induced increases in DOPAC concentrations in the nucleus accumbens. Neither mepyramine nor zolantidine affected basal DOPAC concentrations in the nucleus accumbens. These results indicate that central administration of histamine stimulates mesolimbic DA neurons through an action at the H1 receptor, but has no effect upon the activity of nigrostriatal DA neurons.

  2. Cardiovascular histamine receptors in the domestic chicken.

    Science.gov (United States)

    Chand, N; Eyre, P

    1975-08-01

    The effects of mepyramine (H1-antagonist) and burimamide (H2-antagonist) were studied on histamine, 2-methylhistamine (a selective H1-agonist), 4-methylhistamine (a selective H2-agonist) and acetylcholine-induced changes in systemic arterial and central venous pressure and respiration in anaesthetized chickens. The result of this study suggested a predominance of H1 and some H2 histamine receptors in the cardiovascular system of domestic fowl where both are mediating systemic hypotension. There also appears to be predominance of H1 receptors mediating venous hypertension and respiratory apnoea to large doses of histamine and 2-methylhistamine. In addition, a possible involvement of H2-receptors in the cardiovascular system of chicken is suggested by the finding that burimamide always blocked mepyramine potentiated secondary pressor response to histamine and its analogues.

  3. IS BRAIN HISTAMINE INVOLVED IN DEPRESSION?

    OpenAIRE

    L. Munari; G. Provensi; Passani, M. B.; Galeotti, N; T. Cassano; Blandina, P

    2011-01-01

    Mice unable to synthesize histamine, due to targeted disruption of histidine decarboxylase (HDC) gene or i.c.v. injection of alpha-fluoromethylhistidine (a-FMH, 5 lg), a suicide inhibitor of HDC, were used to test roles for histamine in mediating behavioural changes elicited by different classes of antidepressants, selective serotonin reuptake inhibitors (SSRI) such as citalopram and paroxetine or selective noradrenaline reuptake inhibitors (SNRI), such as reboxetine. The...

  4. Impaired drinking response in histamine H3 receptor knockout mice following dehydration or angiotensin-II challenge.

    Science.gov (United States)

    Yoshimoto, Ryo; Miyamoto, Yasuhisa; Takahashi, Kazuhiko; Kotani, Hidehito; Kanatani, Akio; Tokita, Shigeru

    2006-07-01

    Histamine H3 receptors (H3Rs) are presynaptic receptors that negatively regulate the release of histamine. The present study examined the physiological role of H3Rs in drinking behavior. In water-replete rats, intracerebroventricular (i.c.v.) administration of R-alpha-methylhistamine (RalphaMeHA), an H3R agonist, elicited drinking behavior. In contrast, i.c.v. administration of thioperamide, an H3R inverse agonist, significantly attenuated the drinking behavior elicited by either overnight dehydration or i.c.v. administration of angiotensin-II (AT-II). Inhibition of histamine release with alpha-fluoromethylhistidine, an inhibitor of histidine decarboxylase, did not elicit drinking behavior. Moreover, the inhibitory effects of thioperamide on drinking behavior in water-depleted rats were not mimicked by i.c.v. administration of histamine. These results suggest that the predominant effects of H3Rs on drinking behavior are not mediated by the modulation of histamine release. In H3R-deficient (H3RKO) mice, drinking behavior induced by overnight dehydration or i.c.v. administration of AT-II was significantly impaired compared to wild type mice. Collectively, these observations suggest that brain H3Rs play a pivotal role in drinking behavior in response to dehydration and AT-II, and these effects may be largely independent of the modulation of histaminergic tone.

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

    Science.gov (United States)

    Chikahisa, Sachiko; Kodama, Tohru; Soya, Atsushi; Sagawa, Yohei; Ishimaru, Yuji; Séi, Hiroyoshi; Nishino, Seiji

    2013-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Association of myasthenia gravis with polymorphisms in the gene of histamine N-methyltransferase

    DEFF Research Database (Denmark)

    Kellermayer, Blanka; Polgar, Noemi; Pal, Jozsef

    2013-01-01

    Histamine N-methyltransferase (HNMT) is the main metabolizing enzyme of histamine. Histamine modulates immune responses and plays a role in the pathogenesis of autoimmune disorders.......Histamine N-methyltransferase (HNMT) is the main metabolizing enzyme of histamine. Histamine modulates immune responses and plays a role in the pathogenesis of autoimmune disorders....

  8. Opposite functions of histamine H1 and H2 receptors and H3 receptor in substantia nigra pars reticulata.

    Science.gov (United States)

    Zhou, Fu-Wen; Xu, Jian-Jun; Zhao, Yu; LeDoux, Mark S; Zhou, Fu-Ming

    2006-09-01

    The substantia nigra pars reticulata (SNr) is a key basal ganglia output nucleus. Inhibitory outputs from SNr are encoded in spike frequency and pattern of the inhibitory SNr projection neurons. SNr output intensity and pattern are often abnormal in movement disorders of basal ganglia origin. In Parkinson's disease, histamine innervation and histamine H3 receptor expression in SNr may be increased. However, the functional consequences of these alterations are not known. In this study, whole cell patch-clamp recordings were used to elucidate the function of different histamine receptors in SNr. Histamine increased SNr inhibitory projection neuron firing frequency and thus inhibitory output. This effect was mediated by activation of histamine H1 and H2 receptors that induced inward currents and depolarization. In contrast, histamine H3 receptor activation hyperpolarized and inhibited SNr inhibitory projection neurons, thus decreasing the intensity of basal ganglia output. By the hyperpolarization, H3 receptor activation also increased the irregularity of the interspike intervals or changed the pattern of SNr inhibitory neuron firing. H3 receptor-mediated effects were normally dominated by those mediated by H1 and H2 receptors. Furthermore, endogenously released histamine provided a tonic, H1 and H2 receptor-mediated excitation that helped keep SNr inhibitory projection neurons sufficiently depolarized and spiking regularly. These results suggest that H1 and H2 receptors and H3 receptor exert opposite effects on SNr inhibitory projection neurons. Functional balance of these different histamine receptors may contribute to the proper intensity and pattern of basal ganglia output and, as a consequence, exert important effects on motor control.

  9. InSAR velocity field across the North Anatolian Fault (eastern Turkey): Implications for the loading and release of interseismic strain accumulation

    KAUST Repository

    Cakir, Ziyadin

    2014-10-01

    We use the Persistent Scatterer Interferometric Synthetic Aperture Radar (PS-InSAR) technique with the European Space Agency\\'s Envisat and ERS SAR data acquired on three neighboring descending tracks (T350, T078, and T307) to map the interseismic strain accumulation along a ~225 km long, NW-SE trending section of the North Anatolian Fault that ruptured during the 1939, 1942, and 1943 earthquakes in eastern Turkey. We derive a line-of-sight velocity map of the region with a high spatial resolution and accuracy which, together with the maps of earthquake surface ruptures, shed light on the style of continental deformation and the relationships between the loading and release of interseismic strain along segmented continental strike-slip faults. In contrast with the geometric complexities at the ground surface that appear to control rupture propagation of the 1939 event, modeling of the high-resolution PS-InSAR velocity field reveals a fairly linear and narrow throughgoing shear zone with an overall 20 ± 3 mm/yr slip rate above an unexpectedly shallow 7 ± 2 km locking depth. Such a shallow locking depth may result from the postseismic effects following recent earthquakes or from a simplified model that assumes a uniform degree of locking with depth on the fault. A narrow throughgoing shear zone supports the thick lithosphere model in which continental strike-slip faults are thought to extend as discrete shear zones through the entire crust. Fault segmentation previously reported from coseismic surface ruptures is thus likely inherited from heterogeneities in the upper crust that either preexist and/or develop during coseismic rupture propagation. The geometrical complexities that apparently persist for long periods may guide the dynamic rupture propagation surviving thousands of earthquake cycles.

  10. Histamine concentration is involved in canine valvular disease

    OpenAIRE

    Mitsuhiro Isaka; Masahiko Befu; Nami Matsubara; Mayuko Ishikawa; Yurie Arase; Shinichi Namba

    2014-01-01

    It has been known since many years that there are histamine receptors (H) in the heart. Histamines display chronotropic and inotropic activity, cardiovascular diseases, and are thought to be a systemic inflammatory disease. During heart failure, the histamine concentration is elevated. In addition, H2 blockers prolonged the survival period for human patients with heart failure. The aim of this study was to evaluate whether blood concentration of histamine is associated with canine valvular di...

  11. Control of Histamine-Producing Bacteria and Histamine Formation in Fish Muscle by Trisodium Phosphate.

    Science.gov (United States)

    Bjornsdottir-Butler, Kristin; Green, David P; Bolton, Greg E; McClellan-Green, Patricia D

    2015-06-01

    Scombrotoxin fish poisoning remains the primary cause of seafood poisoning outbreaks despite preventive guidelines. The purpose of this study was to investigate the use of pH for the control of growth and histamine formation by histamine-producing bacteria in fish muscle. We examined pH effects on growth and histamine formation in tuna fish infusion broth and in inoculated tuna and mahi-mahi fish muscle. Histamine production was significantly less for all bacterial strains at pH 8.5 compared to pH 5.5 in tuna fish infusion broth with no significant difference in growth. Elevated pH due to phosphate treatment of fish muscle tissues significantly reduced histamine formation with no effect on the growth of histamine-producing bacteria. This study revealed that phosphate treatment of mahi-mahi and tuna fish muscle resulted in significantly lower histamine production over 4 d of storage at 10 °C. Phosphate treatment of fish muscle may serve as a secondary barrier in addition to FDA recommended time and temperature controls for reducing public health concerns of scombrotoxin fish poisoning.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Histamine H1 and endothelin ETB receptors mediate phospholipase D stimulation in rat brain hippocampal slices.

    Science.gov (United States)

    Sarri, E; Picatoste, F; Claro, E

    1995-08-01

    Different neurotransmitter receptor agonists [carbachol, serotonin, noradrenaline, histamine, endothelin-1, and trans-(1S,3R)-aminocyclopentyl-1,3-dicarboxylic acid (trans-ACPD)], known as stimuli of phospholipase C in brain tissue, were tested for phospholipase D stimulation in [32P]Pi-prelabeled rat brain cortical and hippocampal slices. The accumulation of [32P]phosphatidylethanol was measured as an index of phospholipase D-catalyzed transphosphatidylation in the presence of ethanol. Among the six neurotransmitter receptor agonists tested, only noradrenaline, histamine, endothelin-1, and trans-ACPD stimulated phospholipase D in hippocampus and cortex, an effect that was strictly dependent of the presence of millimolar extracellular calcium concentrations. The effect of histamine (EC50 18 microM) was inhibited by the H1 receptor antagonist mepyramine with a Ki constant of 0.7 nM and was resistant to H2 and H3 receptor antagonists (ranitidine and tioperamide, respectively). Endothelin-1-stimulated phospholipase D (EC50 44 nM) was not blocked by BQ-123, a specific antagonist of the ETA receptor. Endothelin-3 and the specific ETB receptor agonist safarotoxin 6c were also able to stimulate phospholipase D with efficacies similar to that of endothelin-1, and EC50 values of 16 and 3 nM, respectively. These results show that histamine and endothelin-1 stimulate phospholipase D in rat brain through H1 and ETB receptors, respectively.

  14. The carcinine transporter CarT is required in Drosophila photoreceptor neurons to sustain histamine recycling.

    Science.gov (United States)

    Stenesen, Drew; Moehlman, Andrew T; Krämer, Helmut

    2015-12-14

    Synaptic transmission from Drosophila photoreceptors to lamina neurons requires recycling of histamine neurotransmitter. Synaptic histamine is cleared by uptake into glia and conversion into carcinine, which functions as transport metabolite. How carcinine is transported from glia to photoreceptor neurons remains unclear. In a targeted RNAi screen for genes involved in this pathway, we identified carT, which encodes a member of the SLC22A transporter family. CarT expression in photoreceptors is necessary and sufficient for fly vision and behavior. Carcinine accumulates in the lamina of carT flies. Wild-type levels are restored by photoreceptor-specific expression of CarT, and endogenous tagging suggests CarT localizes to synaptic endings. Heterologous expression of CarT in S2 cells is sufficient for carcinine uptake, demonstrating the ability of CarT to utilize carcinine as a transport substrate. Together, our results demonstrate that CarT transports the histamine metabolite carcinine into photoreceptor neurons, thus contributing an essential step to the histamine-carcinine cycle.

  15. Neuronal glucoprivation enhances hypothalamic histamine turnover in rats.

    Science.gov (United States)

    Oohara, A; Yoshimatsu, H; Kurokawa, M; Oishi, R; Saeki, K; Sakata, T

    1994-08-01

    Histamine (HA) turnover in the rat hypothalamus following insufficient energy supply due to glucoprivation was examined after administration of insulin or 2-deoxy-D-glucose (2-DG). HA turnover was assessed by accumulation of tele-methylhistamine (t-MH), a major metabolite of brain HA, following administration of pargyline. Intraperitoneal injection of 1, 2, and 4 U/kg of insulin, which had no influence on steady-state levels of HA and t-MH, increased pargyline-induced accumulation of t-MH. Accumulation of t-MH due to pargyline was inversely related to the concomitant plasma glucose concentration after different doses of insulin. The level of t-MH accumulated by pargyline did not change compared with that of controls, when a euglycemic condition was maintained or insulin at a dose of 6 mU per rat was infused into the third cerebroventricle. Intracerebroventricular infusion of 24 mumol per rat of 2-DG, which had no influence on steady-state levels of HA and t-MH, increased the level of t-MH enhanced by pargyline. The results indicate that an increase in hypothalamic HA turnover in response to glucoprivation may be involved in homeostatic regulation of energy metabolism in the brain.

  16. Differential inhibitory effects of 2-azafluorenones on PI-PLC activation but not on PC-PLC- or PC-PLD-activation induced by histamine, PAF, PMA or A23187 in C6 glioma cells.

    Science.gov (United States)

    Wang, Hai-Long; Wang, Li-Chuan; Wei, Jiann-Wu

    2013-02-28

    In this study, C6 glioma cells were used to test the effects of 2-azafluorenone and its related compounds on membrane phosphatidylinositol (PI) and phosphatidylcholine (PC) turnover. An increase of [³H]-labeled inositol phosphate (IP1) formation by histamine (100 μM) or A23187 (100 nM) via the activation of phosphatidylinositol-specific phospholipase C (PI-PLC) to breakdown labeled substrate was observed, and this effect could be partially blocked by about half at 100 μM of 2-azafluorenones. Histamine induced the increase of IP1 formation, but failed to cause an increase in extracellularly releasing of [3H]choline metabolites, or intracellular accumulation of [³H]phosphscholine. However, platelet activation factor (PAF) from 0.2 to 1 μM, and phorbol 12-myristate-13-acetate (PMA) at 1 μM caused an increase in extracellularly releasing of [³H]choline metabolites, and intracellular accumulation of [³H]phosphocholine via the activation on phosphatidylcholine (PC)-PLC. These responses of PAF and PMA were not affected by 2-azafluorenone or 4-methyl-2-azafluorenone even at high concentration (10⁻⁴ M). A23187 induced an increase of intracellular [³H]choline release via the activation of PCphospholipase D (PLD). This increasing effect of 100 nM A23187 was not affected by 2-azafluorenone or 4-methyl-2-azafluorenone even at a high concentration of 10⁻⁴ M. In summary, the inhibitory effect of 2-azafluorenone and its related compound 4-methyl-2-azafluorenone was observed selectively on PIPLC, but not on PC-PLC or PC-PLD based on changes of products after the activation of these enzymes.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kandasamy, S.B.; Hunt, W.A. (Armed Forces Radiobiology Research Institute, Bethesda, MD (USA))

    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.

  18. Effects of histamine on atrial and ventricular contractility in the canine isovolumic heart.

    Science.gov (United States)

    Vidrio, H; Priola, D V

    1990-03-01

    The effects of intracoronary administration of histamine on atrial and ventricular contractility were determined in a paced canine isovolumic heart preparation. Contractility was assessed by recording the pressure developed in saline-filled balloons placed in each of the four cardiac chambers. At doses above 0.1 mg and up to 100 mg histamine produced dose-related positive inotropic responses in all chambers. These were preceded by transient negative effects. The positive responses were not affected by a combination of H1 and H2 receptor antagonists antazoline and cimetidine but were almost completely abolished by the beta adrenoceptor blocker timolol. The negative responses were uninfluenced by either treatment. It was concluded that, in the canine isovolumic heart not subjected to complicating chronotropic and extracardiac factors, moderate doses of histamine are devoid of inotropic effects. Higher doses do produce myocardial stimulation, not mediated by histamine receptors, but probably due to norepinephrine release. These responses are preceded by transient non-specific depressant effects.

  19. An investigation into the roles of histamine receptors in the control of human nasal blockage

    OpenAIRE

    Taylor-Clark, T. E.

    2004-01-01

    Allergic rhinitis is an allergic disease of the nose and, in sensitized individuals, is caused by inhaled innocuous particles such as pollen and house dust mite faeces. Allergen binds IgE on the surface of nasal mast cells, causing mast cell activation and degranulation, resulting in the release of inflammatory substances that are responsible for the symptoms of allergic rhinitis — sneezing, rhinorrhea, pruritus and nasal blockage. In this thesis, the mechanisms by which histamine, a mast cel...

  20. Identification and characterization of ZEL-H16 as a novel agonist of the histamine H3 receptor.

    Directory of Open Access Journals (Sweden)

    Ying Shi

    Full Text Available The histamine H3 receptor (H3R has been recognized as a promising target for the treatment of various central and peripheral nervous system diseases. In this study, a non-imidazole compound, ZEL-H16, was identified as a novel histamine H3 receptor agonist. ZEL-H16 was found to bind to human H3R with a Ki value of approximately 2.07 nM and 4.36 nM to rat H3R. Further characterization indicated that ZEL-H16 behaved as a partial agonist on the inhibition of forskolin-stimulated cAMP accumulation (the efficacy was 60% of that of histamine and activation of ERK1/2 signaling (the efficacy was 50% of that of histamine at H3 receptors, but acted as a full agonist just like histamin in the guinea-pig ileum contraction assay. These effects were blocked by pertussis toxin and H3 receptor specific antagonist thioperamide. ZEL-H16 showed no agonist or antagonist activities at the cloned human histamine H1, H2, and H4 receptors and other biogenic amine GPCRs in the CRE-driven reporter assay. Furthermore, our present data demonstrated that treatment of ZEL-H16 resulted in intensive H3 receptor internalization and delayed recycling to the cell surface as compared to that of control with treatment of histamine. Thus, ZEL-H16 is a novel and potent nonimidazole agonist of H3R, which might serve as a pharmacological tool for future investigations or as possible therapeutic agent of H3R.

  1. Identification and characterization of ZEL-H16 as a novel agonist of the histamine H3 receptor.

    Science.gov (United States)

    Shi, Ying; Sheng, Rong; Zhong, Tingting; Xu, Yu; Chen, Xiaopan; Yang, Dong; Sun, Yi; Yang, Fenyan; Hu, Yongzhou; Zhou, Naiming

    2012-01-01

    The histamine H3 receptor (H3R) has been recognized as a promising target for the treatment of various central and peripheral nervous system diseases. In this study, a non-imidazole compound, ZEL-H16, was identified as a novel histamine H3 receptor agonist. ZEL-H16 was found to bind to human H3R with a Ki value of approximately 2.07 nM and 4.36 nM to rat H3R. Further characterization indicated that ZEL-H16 behaved as a partial agonist on the inhibition of forskolin-stimulated cAMP accumulation (the efficacy was 60% of that of histamine) and activation of ERK1/2 signaling (the efficacy was 50% of that of histamine) at H3 receptors, but acted as a full agonist just like histamin in the guinea-pig ileum contraction assay. These effects were blocked by pertussis toxin and H3 receptor specific antagonist thioperamide. ZEL-H16 showed no agonist or antagonist activities at the cloned human histamine H1, H2, and H4 receptors and other biogenic amine GPCRs in the CRE-driven reporter assay. Furthermore, our present data demonstrated that treatment of ZEL-H16 resulted in intensive H3 receptor internalization and delayed recycling to the cell surface as compared to that of control with treatment of histamine. Thus, ZEL-H16 is a novel and potent nonimidazole agonist of H3R, which might serve as a pharmacological tool for future investigations or as possible therapeutic agent of H3R.

  2. Pharmacological characterisation of cardiovascular histamine receptors in man in vivo.

    Science.gov (United States)

    Boyce, M J

    1982-09-01

    Data from pharmacological studies carried out in healthy subjects using systemic histamine or impromidine and their antagonists are reviewed. Exogenous histamine by rapid injection appears to stimulate only H1-receptors. Chlorpheniramine alone antagonised the responses to histamine. The effects of cardiovascular H2-receptor stimulation are demonstrated best by a sustained and large dose of histamine given by infusion. If it be considered desirable to antagonise all the cardiovascular responses to endogenous histamine, the available pharmacological data in man suggest this would be achieved best by a combination of an H1-and H2-receptor antagonist.

  3. Endogenous central histamine-induced reversal of critical hemorrhagic hypotension in rats: studies with L-histidine.

    Science.gov (United States)

    Jochem, Jerzy

    2003-10-01

    Activation of the histaminergic system is characteristic of response to the action of adverse or potentially dangerous stimuli that disturb circulatory homeostasis, such as dehydration and changes in blood pressure. Previous study demonstrates that inhibition of histamine N-methyltransferase, which catabolizes histamine released from neurons, leads to the increase in endogenous central histamine concentrations and to the reversal of critical hemorrhagic hypotension. In the present study, the influence of intraperitoneal loading with histamine precursor L-histidine on central cardiovascular regulation was studied in a model of irreversible pressure-controlled hemorrhagic shock. Experiments were carried out in male Wistar rats anesthetized with ketamine/xylazine subjected to critical hemorrhagic hypotension of 20 to 25 mmHg, which resulted in the death of all control saline-treated animals within 30 min. L-histidine administered in 5 min of critical hypotension produced dose-dependent increases in mean arterial pressure and heart rate (100-500 mg/kg), and a 100% survival rate of 2 h (500 mg/kg), whereas in normotensive animals, it did not influence cardiovascular parameters. The resuscitating effect of L-histidine (500 mg/kg) was associated with increases in histamine concentrations in the cerebral cortex (0.97 +/- 0.11 nmol/g of wet tissue vs. 0.67 +/- 0.22 nmol/g of wet tissue; P<0.05), hypothalamus (4.78 +/- 0.58 nmol/g of wet tissue vs. 4.08 +/- 0.43 nmol/g of wet tissue; P<0.01), and medulla oblongata (0.55 +/- 0.18 nmol/g of wet tissue vs. 0.34 +/- 0.09 nmol/g of wet tissue; P<0.05), as well as with no changes in plasma histamine concentrations in comparison with the saline-treated group 20 min after injection. Pretreatment with (S)-alpha-fluoromethylhistidine (alpha-FMH, 0.5 mg intracerebroventricularly), an irreversible inhibitor of L-histidine decarboxylase, produced a decrease in central histamine concentrations and diminished volumes of blood required to

  4. 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

    Histamine, a toxic compound that is formed by the decarboxylation of histidine through the action of microbial decarboxylases, can accumulate in fermented food products. From a total of 69 Streptococcus thermophilus strains screened, two strains, CHCC1524 and CHCC6483, showed the capacity...... 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...... 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...

  5. Synthesis and evaluation of structurally constrained quinazolinone derivatives as potent and selective histamine H3 receptor inverse agonists.

    Science.gov (United States)

    Nagase, Tsuyoshi; Mizutani, Takashi; Sekino, Etsuko; Ishikawa, Shiho; Ito, Sayaka; Mitobe, Yuko; Miyamoto, Yasuhisa; Yoshimoto, Ryo; Tanaka, Takeshi; Ishihara, Akane; Takenaga, Norihiro; Tokita, Shigeru; Sato, Nagaaki

    2008-11-13

    A series of structurally constrained derivatives of the potent H 3 inverse agonist 1 was designed, synthesized, and evaluated as histamine H 3 receptor inverse agonists. As a result, the N-cyclobutylpiperidin-4-yloxy group as in 2f was identified as an optimal surrogate structure for the flexible 1-pyrrolidinopropoxy group of 1. Subsequent optimization of the quinazolinone core of 2f revealed that substitution at the 5-position of the quinazolinone ring influences potency. Representative derivatives 5a and 5s showed improved potency in a histamine release assay in rats and a receptor occupancy assay in mice.

  6. Klebsiella pneumoniae produces no histamine: Raoultella planticola and Raoultella ornithinolytica strains are histamine producers.

    Science.gov (United States)

    Kanki, Masashi; Yoda, Tomoko; Tsukamoto, Teizo; Shibata, Tadayoshi

    2002-07-01

    Histamine fish poisoning is caused by histamine-producing bacteria (HPB). Klebsiella pneumoniae and Klebsiella oxytoca are the best-known HPB in fish. However, 22 strains of HPB from fish first identified as K. pneumoniae or K. oxytoca by commercialized systems were later correctly identified as Raoultella planticola (formerly Klebsiella planticola) by additional tests. Similarly, five strains of Raoultella ornithinolytica (formerly Klebsiella ornithinolytica) were isolated from fish as new HPB. R. planticola and R. ornithinolytica strains were equal in their histamine-producing capabilities and were determined to possess the hdc genes, encoding histidine decarboxylase. On the other hand, a collection of 61 strains of K. pneumoniae and 18 strains of K. oxytoca produced no histamine.

  7. Effects of anti-histamine treatment on liver injury triggered by small intestinal ischemia reperfusion in rats.

    Science.gov (United States)

    Huang, Pin-Jie; Gan, Xiao-Liang; Liu, Jian-Pei; Liu, De-Zhao; Wang, Yan-Ling; Hei, Zi-Qing

    2014-10-31

    Mast cell (MC) degranulation has been implicated in small intestinal ischemia reperfusion (IIR) injury, therein, inhibiting overproduction of histamine released from activated MC may provide promising strategies against IIR-mediated liver injuries. The aim of the present study was to explore whether anti-histamine treatment contribute to attenuating IIR-mediated liver injury. Adult SD rats were randomized into sham-operated group (S group), sole IIR group (IIR group), and IIR treated with Ketotifen, a histamine antagonist (IIR+K group), Cromolyn Sodium, a MC stabilizer (IIR+C group), and Compound 48/80, a MC degranulator (IIR+CP group), respectively. IIR was induced by superior mesenteric artery occlusion for 75 min followed by 4 h of reperfusion. The agents were intravenously administrated 5 min before reperfusion to induce different levels of histamine. Subsequently, serum concentrations of ALT, AST and histamine; levels of LDH,TNF-α, IL-8 and MDA as well as SOD activities in the liver were assessed. Histopathologic changes were also evaluated. IIR resulted in severe liver injury as demonstrated by significant increases in injury scores, with concomitant significant increases in serum ALT, AST and histamine levels, as well as LDH, TNF-α, IL-8, and MDA levels in the liver, accompanied by reduction in SOD activities (all P IIR vs. S). Treatments by Ketotifen and Cromolyn Sodium similarly markedly alleviated IIR-mediated liver injury as confirmed by significant reduction of the above biomedical changes whereas Compound 48/80 further aggravated IIR-mediated liver injury by dramatically enhancing the above biomedical changes. Data of our study suggest that anti-histamine treatments may provide promising benefits in alleviating liver injury triggered by IIR.

  8. Determination of trans- and cis-urocanic acid in relation to histamine, putrescine, and cadaverine contents in tuna (Auxis Thazard) at different storage temperatures.

    Science.gov (United States)

    Zare, Davood; Muhammad, Kharidah; Bejo, Mohd Hair; Ghazali, H M

    2015-02-01

    Scombroid fish poisoning is usually associated with consumption of fish containing high levels of histamine. However, reports indicate that some cases have responded to antihistamine therapy while ingested histamine levels in these cases were low. Potentiation of histamine toxicity by some biogenic amines, and release of endogenous histamine by other compounds such as cis-urocanic acid (UCA) are some hypotheses that have been put forth to explain this anomaly. Very little is known about the effects of storage conditions on the production of both UCA isomers and biogenic amines in tuna. Thus, the production of trans- and cis-UCA, histamine, putrescine, and cadaverine in tuna during 15 d of storage at 0, 3, and 10 °C and 2 d storage at ambient temperature were monitored. The initial trans- and cis-UCA contents in fresh tuna were 2.90 and 1.47 mg/kg, respectively, whereas the levels of putrescine and cadaverine were less than 2 mg/kg, and histamine was not detected. The highest levels of trans- and cis-UCA were obtained during 15 d storage at 3 °C (23.74 and 21.79 mg/kg, respectively) while the highest concentrations of histamine (2796 mg/kg), putrescine (220.32 mg/kg) and cadaverine (1045.20 mg/kg) were obtained during storage at room temperature, 10 and 10 °C, respectively. Histamine content increased considerably during storage at 10 °C whereas trans- and cis-UCA contents changed slightly. The initial trans-UCA content decreased during storage at ambient temperature. Thus, unlike histamine, concentrations of trans- and cis-UCA did not result in elevated levels during storage of tuna.

  9. [Level of histamine in supernatants from the basophil activation test: applications to hymenoptera allergy and drug allergy--preliminary study].

    Science.gov (United States)

    Tamim, S; Lauret, M G; Drouet, M; Sabbah, A

    1999-02-01

    Histamine Release technic consists in calculating histamine liberated by blood cells in touch with an allergen. To this day, this method is only used in Hymenoptera venom allergy diagnosis. The principle of this study is to measure histamine released by activated basophils in surnageons of Basophil Activation Test (BAT) for different allergens: Hymenoptera venoms: Bee, White Faced Hornet, Vespula Wasp. Drugs: Cefaperos, Clamoxyl, Alfatil, Rapifen, Diprivan, Nesdonal, Mivacron. A threshold of positivity (amplification factor in comparison with the control) is determined for these two classes of allergens: 45 for Hymenoptera venoms and 9 for drugs. These results, compared to the other diagnosis technics (Histamine Release, Basophil Activation Test, Prick Tests) discloses very high correlation rates in each case. This method seems to be a reliable method for Hymenoptera venom allergy diagnosis and for drugs allergy diagnosis too. However, this study is based on a few number of patients, so a significant statistic conclusion can't be expressed but it opens an interesting way of research.

  10. Compound 48/80, a histamine-depleting agent, blocks the protective effect of morphine against electroconvulsive shock in mice

    Directory of Open Access Journals (Sweden)

    Karadag C.H.

    2000-01-01

    Full Text Available We have shown that morphine has an anticonvulsive effect against maximal electroconvulsive shock (MES in mice, and this effect is antagonized by histamine H1-receptor antagonists. Brain histamine is localized both in neurons and in mast cells, and morphine is known to enhance the turnover of neuronal histamine and to release histamine from mast cells. In the present experiments, compound 48/80 was injected chronically (0.5 mg/kg on day 1, 1 mg/kg on day 2, 2 mg/kg on day 3, 3 mg/kg on day 4, and 4 mg/kg on day 5, twice daily, ip to deplete mast cell contents. Morphine (0.001-10 mg/kg, ip; N = 20 produced a dose-dependent anticonvulsive effect against MES seizure in mice with non-depleted mast cells, whereas it did not exert any anticonvulsive effect in mice with depleted mast cells. These results indicate that morphine produces its anticonvulsive effect against maximal electroconvulsive shock in mice by liberating histamine from mast cells.

  11. Role of the Histamine H3 Receptor in the Central Nervous System.

    Science.gov (United States)

    Schlicker, Eberhard; Kathmann, Markus

    2016-10-28

    The Gi/o protein-coupled histamine H3 receptor is distributed throughout the central nervous system including areas like cerebral cortex, hippocampus and striatum with the density being highest in the posterior hypothalamus, i.e. the area in which the histaminergic cell bodies are located. In contrast to the other histamine receptor subtypes (H1, H2 and H4), the H3 receptor is located presynaptically and shows a constitutive activity. In detail, H3 receptors are involved in the inhibition of histamine release (presynaptic autoreceptor), impulse flow along the histaminergic neurones (somadendritic autoreceptor) and histamine synthesis. Moreover, they occur as inhibitory presynaptic heteroreceptors on serotoninergic, noradrenergic, dopaminergic, glutamatergic, GABAergic and perhaps cholinergic neurones. This review shows for four functions of the brain that the H3 receptor represents a brake against the wake-promoting, anticonvulsant and anorectic effect of histamine (via postsynaptic H1 receptors) and its procognitive activity (via postsynaptic H1 and H2 receptors). Indeed, H1 agonists and H3 inverse agonists elicit essentially the same effects, at least in rodents; these effects are opposite in direction to those elicited by brain-penetrating H1 receptor antagonists in humans. Although the benefit for H3 inverse agonists for the symptomatic treatment of dementias is inconclusive, several members of this group have shown a marked potential for the treatment of disorders associated with excessive daytime sleepiness. In March 2016, the European Commission granted a marketing authorisation for pitolisant (Wakix(R)) (as the first representative of the H3 inverse agonists) for the treatment of narcolepsy.

  12. Mast cell histamine promotes the immunoregulatory activity of myeloid-derived suppressor cells.

    Science.gov (United States)

    Martin, Rebecca K; Saleem, Sheinei J; Folgosa, Lauren; Zellner, Hannah B; Damle, Sheela R; Nguyen, Giang-Kim T; Ryan, John J; Bear, Harry D; Irani, Anne-Marie; Conrad, Daniel H

    2014-07-01

    It has been shown recently that MCs are required for differential regulation of the immune response by granulocytic versus monocytic MDSCs. Granulocytic MDSCs promoted parasite clearance, whereas monocytic MDSCs enhanced tumor progression; both activities were abrogated in MC-deficient mice. Herein, we demonstrate that the lack of MCs also influences MDSC trafficking. Preferential trafficking to the liver was not seen in MC-deficient mice. In addition, evidence that the MC mediator histamine was important in MDSC trafficking and activation is also shown. MDSCs express HR1-3. Blockade of these receptors by HR1 or HR2 antagonists reversed the histamine enhancement of MDSC survival and proliferation observed in cell culture. In addition, histamine differentially influenced Arg1 and iNOS gene expression in MDSCs and greatly enhanced IL-4 and IL-13 message, especially in granulocytic MDSCs. Evidence that histamine influenced activity seen in vitro translated to in vivo when HR1 and HR2 antagonists blocked the effect of MDSCs on parasite expulsion and tumor metastasis. All of these data support the MDSC-mediated promotion of Th2 immunity, leading to the suggestion that allergic-prone individuals would have elevated MDSC levels. This was directly demonstrated by looking at the relative MDSC levels in allergic versus control patients. Monocytic MDSCs trended higher, whereas granulocytic MDSCs were increased significantly in allergic patients. Taken together, our studies indicate that MCs and MC-released histamine are critical for MDSC-mediated immune regulation, and this interaction should be taken into consideration for therapeutic interventions that target MDSCs.

  13. Studies on the pharmacology of the novel histamine H3 receptor agonist Sch 50971.

    Science.gov (United States)

    Hey, J A; Aslanian, R; Bolser, D C; Chapman, R W; Egan, R W; Rizzo, C A; Shih, N Y; Fernandez, X; McLeod, R L; West, R; Kreutner, W

    1998-09-01

    Experiments were performed to characterize the pharmacology of Sch 50971 ((+)-trans-4-(4(R)-methyl-3(R)-pyrolidinyl)-1H-imidazole dihydrochloride, CAS 167610-28-8), a novel histamine H3 receptor agonist. The activity of Sch 50971 was compared with that of (R)-alpha-methylhistamine (CAS 75614-87-8), a potent and moderately selective agonist of histamine H3 receptors, in a series of in vitro and in vivo assays. Sch 50971 is a high affinity, selective H3 receptor agonist in vitro and in vivo. Sch 50971 inhibits [3H]-N-alpha-methylhistamine (CAS 673-50-7) binding to the histamine H3 receptor in human brain (Ki = 5.0 nmol/l) and guinea pig brain (Ki = 2.5 nmol/l). Sch 50971 also inhibits electric field stimulated guinea pig ileum contractions (pD2 = 7.47) and decreases [3H]-norepinephrine (CAS 51-41-2) release (pD2 = 7.48) from guinea pig pulmonary artery by activation of presynaptic inhibitory H3 receptors. The in vitro effects of Sch 50971 are antagonized by low concentrations of a selective H3 antagonist, thioperamide (CAS 106243-16-7). Sch 50971 has low affinity (IC50's > 10 mumol/l) for histamine H1, dopamine D1 and D2, serotonin 5-HT2 and muscarinic cholinergic receptors. It also does not exhibit histamine H2-antagonist activity. In guinea pigs and cats, Sch 50971 exhibits in vivo H3 agonist activity. Sch 50971 inhibits sympathetic hypertension evoked by stimulation of the medulla oblongata in anesthetized guinea pigs (ED30 = 0.3 mg/kg i.v., ED30 = 1.0 mg/kg i.d.). Sch 50971 also inhibits the effects of sympathetic nerve stimulation on nasal resistance in cats. In these assays, Sch 50971 exhibits an efficacy and potency comparable to H3-agonist (R)-alpha-methylhistamine. However, under in vivo conditions, Sch 50971 does not exhibit histamine H1-mediated responses that are seen with (R)-alpha-methylhistamine at doses close to those that produce H3 effects. Therefore, Sch 50971 is a novel, potent and selective agonist of histamine H3 receptors with an improved in

  14. Energy release, beam attenuation radiation damage, gas production and accumulation of long-lived activity in Pb, Pb-Bi and Hg targets

    Energy Technology Data Exchange (ETDEWEB)

    Shubin, Yu.N. [IPPE, Obninsk (Russian Federation)

    1996-06-01

    The calculation and analysis of the nuclei concentrations and long-lived residual radioactivity accumulated in Pb, Pb-Bi and Hg targets irradiated by 800 MeV, 30 mA proton beam have been performed. The dominating components to the total radioactivity of radionuclides resulting from fission and spallation reactions and radiative capture by both target nuclei and accumulated radioactive nuclei for various irradiation and cooling times were analyzed. The estimations of spectral component contributions of neutron and proton fluxes to the accumulated activity were carried out. The contributions of fission products to the targets activity and partial activities of main long-lived fission products to the targets activity and partial activities of main long-lived fission products were evaluated. The accumulation of Po isotopes due to reactions induced by secondary alpha-particles were found to be important for the Pb target as compared with two-step radiative capture. The production of Tritium in the targets and its contribution to the total targets activity was considered in detail. It is found that total activities of both targets are close to one another.

  15. Insufficient intake of L-histidine reduces brain histamine and causes anxiety-like behaviors in male mice.

    Science.gov (United States)

    Yoshikawa, Takeo; Nakamura, Tadaho; Shibakusa, Tetsuro; Sugita, Mayu; Naganuma, Fumito; Iida, Tomomitsu; Miura, Yamato; Mohsen, Attayeb; Harada, Ryuichi; Yanai, Kazuhiko

    2014-10-01

    L-histidine is one of the essential amino acids for humans, and it plays a critical role as a component of proteins. L-histidine is also important as a precursor of histamine. Brain histamine is synthesized from L-histidine in the presence of histidine decarboxylase, which is expressed in histamine neurons. In the present study, we aimed to elucidate the importance of dietary L-histidine as a precursor of brain histamine and the histaminergic nervous system. C57BL/6J male mice at 8 wk of age were assigned to 2 different diets for at least 2 wk: the control (Con) diet (5.08 g L-histidine/kg diet) or the low L-histidine diet (LHD) (1.28 g L-histidine/kg diet). We measured the histamine concentration in the brain areas of Con diet-fed mice (Con group) and LHD-fed mice (LHD group). The histamine concentration was significantly lower in the LHD group [Con group vs. LHD group: histamine in cortex (means ± SEs): 13.9 ± 1.25 vs. 9.36 ± 0.549 ng/g tissue; P = 0.002]. Our in vivo microdialysis assays revealed that histamine release stimulated by high K(+) from the hypothalamus in the LHD group was 60% of that in the Con group (P = 0.012). However, the concentrations of other monoamines and their metabolites were not changed by the LHD. The open-field tests showed that the LHD group spent a shorter amount of time in the central zone (87.6 ± 14.1 vs. 50.0 ± 6.03 s/10 min; P = 0.019), and the light/dark box tests demonstrated that the LHD group spent a shorter amount of time in the light box (198 ± 8.19 vs. 162 ± 14.1 s/10 min; P = 0.048), suggesting that the LHD induced anxiety-like behaviors. However, locomotor activity, memory functions, and social interaction did not differ between the 2 groups. The results of the present study demonstrated that insufficient intake of histidine reduced the brain histamine content, leading to anxiety-like behaviors in the mice.

  16. In vitro study of histamine and histamine receptor ligands influence on the adhesion of purified human eosinophils to endothelium.

    Science.gov (United States)

    Grosicki, Marek; Wójcik, Tomasz; Chlopicki, Stefan; Kieć-Kononowicz, Katarzyna

    2016-04-15

    It is a well-known fact that histamine is involved in eosinophil-dependent inflammatory responses including cellular chemotaxis and migration. Nevertheless, the relative role of histamine receptors in the mechanisms of eosinophils adhesion to endothelial cells is not known. Therefore the aim of presented study was to examine the effect of selective histamine receptors ligands on eosinophils adhesion to endothelium. For that purpose the highly purified human eosinophils have been isolated from the peripheral blood. The viability and functional integrity of isolated eosinophils have been validated in several tests. Histamine as well as 4-methylhistamine (selective H4 agonist) in concentration-dependent manner significantly increased number of eosinophils that adhere to endothelium. Among the selective histamine receptors antagonist or H1 inverse agonist only JNJ7777120 (histamine H4 antagonist) and thioperamide (dual histamine H3/H4 antagonist) had direct effect on eosinophils adhesion to endothelial cells. Antagonists of H1 (diphenhydramine, mepyramine) H2 (ranitidine and famotidine) and H3 (pitolisant) histamine receptors were ineffective. To the best of our knowledge, this is the first study to demonstrate that histamine receptor H4 plays a dominant role in histamine-induced eosinophils adhesion to endothelium.

  17. 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 Gq/11 -protein-coupled human histamine H1 receptors internalized via clathrin-dependent mechanisms upon stimulation with histamine. However, the molecular determinants of H1 receptors responsible for agonist-induced internalization remain unclear. In this study, we evaluated the roles of the intracellular C-terminal of human histamine H1 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 H1 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 H1 receptors, which only comprises 17 amino acids (Cys471-Ser487), plays crucial roles in both clathrin-dependent internalization of H1 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.

  18. 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...

  19. Depletion of brain histamine produces regionally selective protection against thiamine deficiency-induced lesions in the rat.

    Science.gov (United States)

    Langlais, Philip J; McRee, Robert Carter; Nalwalk, Julia A; Hough, Lindsay B

    2002-09-01

    Breakdown of the blood brain barrier and the subsequent accumulation of free radicals, lactate, and glutamate appear to be the immediate causes of thiamine deficiency (TD)-induced damage to thalamus. The mechanisms triggering these events are unknown but recent evidence suggests an important role of histamine. We therefore studied the effects of histamine depletion on thalamic lesions in the pyrithiamine-induced thiamine deficient (PTD) rat. Chronic intracerebroventricular (i.c.v., 7 days) infusion of alpha-fluoromethylhistidine (FMH), combined with bilateral ibotenate destruction of the histamine-containing neurons in the tuberomammillary (TM) nucleus and bolus i.c.v. infusion of 48/80, a potent mast cell degranulating agent, was used to deplete brain histamine levels. PTD rats receiving combined FMH + 48/80 + TM lesions developed acute neurological symptoms, including spontaneous seizures, approximately 1 day earlier than PTD rats treated with i.c.v. infusion of vehicle and sham lesions of the TM. When examined 1 week after restoration of thiamine, the PTD vehicle + sham lesion animals contained severe neuronal loss and gliosis in midline, intralaminar, ventral, lateral, and posterior nuclei. PTD animals treated with FMH + 48/80 + TM lesions had little evidence of neuronal loss or microglial proliferation in thalamus except in the gelatinosus and anteroventral nuclei, in which there was complete neuronal loss. These data demonstrate a significant and regionally selective role of histamine in the development of thalamic lesions in a rat model of Wernicke's encephalopathy. Furthermore, these data suggest either a dissociation between seizures and thalamic lesions or a significant role of histamine in seizure-related damage to the thalamus.

  20. Positive inotropic effects of histamine in anaesthetized dogs.

    OpenAIRE

    Einstein, R.; Mihailidou, A. S.; Richardson, D.P.

    1987-01-01

    1 The cardiovascular effects of histamine were examined in dogs anaesthetized with pentobarbitone 2 The effect of histamine on heart rate, blood pressure, left ventricular pressure, dP/dtmax and dP/dt: IIT (integrated isometric tension) was compared in the presence and absence of autonomic reflexes and blood pressure control. 3 In innervated animals with no attempt to control blood pressure, histamine produced dose-dependent decreases in blood pressure and heart rate and either positive or ne...

  1. Histamine revisited: Role in acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Prasan R Bhandari

    2013-01-01

    Full Text Available Histamine dihydrochloride (HDC is derived from biogenic amine histamine. It suppresses the production of reactive oxygen species which inhibits the stimulation of T cells and natural killer (NK cells. Co-administration of the cytokine interleukin (IL-2 and HDC assists the activation of T cells and NK cells by IL-2, causing in the destruction of cancer cells, including those of acute myeloid leukemia (AML. A significantly longer leukemia-free survival (LFS; primary endpoint was demonstrated in a phase III trial in adult patients with AML in first or subsequent remission, in those who received subcutaneous HDC and concomitant subcutaneous IL-2 as maintenance therapy compared to that of patients receiving no treatment. However, the difference in overall survival (OS between the two groups was not significant. Patients had acceptable levels of adverse effects. Thus, HDC in addition to IL-2 appears to be a useful maintenance therapy option for adult patients with AML in remission.

  2. Histamine resets the circadian clock in the suprachiasmatic nucleus through the H1R-CaV 1.3-RyR pathway in the mouse.

    Science.gov (United States)

    Kim, Yoon Sik; Kim, Young-Beom; Kim, Woong Bin; Yoon, Bo-Eun; Shen, Feng-Yan; Lee, Seung Won; Soong, Tuck-Wah; Han, Hee-Chul; Colwell, Christopher S; Lee, C Justin; Kim, Yang In

    2015-10-01

    Histamine, a neurotransmitter/neuromodulator implicated in the control of arousal state, exerts a potent phase-shifting effect on the circadian clock in the rodent suprachiasmatic nucleus (SCN). In this study, the mechanisms by which histamine resets the circadian clock in the mouse SCN were investigated. As a first step, Ca(2+) -imaging techniques were used to demonstrate that histamine increases intracellular Ca(2+) concentration ([Ca(2+) ]i ) in acutely dissociated SCN neurons and that this increase is blocked by the H1 histamine receptor (H1R) antagonist pyrilamine, the removal of extracellular Ca(2+) and the L-type Ca(2+) channel blocker nimodipine. The histamine-induced Ca(2+) transient is reduced, but not blocked, by application of the ryanodine receptor (RyR) blocker dantrolene. Immunohistochemical techniques indicated that CaV 1.3 L-type Ca(2+) channels are expressed mainly in the somata of SCN cells along with the H1R, whereas CaV 1.2 channels are located primarily in the processes. Finally, extracellular single-unit recordings demonstrated that the histamine-elicited phase delay of the circadian neural activity rhythm recorded from SCN slices is blocked by pyrilamine, nimodipine and the knockout of CaV 1.3 channel. Again, application of dantrolene reduced but did not block the histamine-induced phase delays. Collectively, these results indicate that, to reset the circadian clock, histamine increases [Ca(2+) ]i in SCN neurons by activating CaV 1.3 channels through H1R, and secondarily by causing Ca(2+) -induced Ca(2+) release from RyR-mediated internal stores.

  3. Cardiovascular response to histamine during normoxaemia and hypoxaemia in piglets.

    Science.gov (United States)

    Taylor, B J

    1989-02-01

    The cardiovascular effects of exogenously administered histamine were investigated in conscious newborn piglets aged 10-11 days during normoxia (21% (v/v) O2) and during isocapneic alveolar hypoxia (10% O2, 3% CO2, 87% N2) to determine its influence on preexisting vascular tone. In the first set of experiments (n = 6), four histamine doses (1,10,50,100 micrograms/kg) were tested in sequence during normoxia. Histamine was injected intravenously and cardiovascular variables were recorded. Heart rate increased at all doses studied. Pulmonary and systemic arterial pressures, cardiac output and stroke volume were unchanged at the low histamine doses (1 and 10 micrograms), but all decreased at the high doses (50 and 100 micrograms). Pulmonary and systemic vascular resistances were unchanged at each dose. In the second set of experiments (n = 7), two histamine doses (1 and 5 micrograms/kg) were administered during alveolar hypoxia. Hypoxia caused increases in heart rate and pulmonary arterial pressure and resistance. After injection of each dose of histamine, pulmonary pressure and resistance decreased but remained higher than baseline. No other measured cardiovascular variables were altered. Thus, during normoxia histamine did not alter vascular tone, but high doses did adversely affect myocardial function. During alveolar hypoxia histamine caused weak pulmonary vasodilation at doses that did not alter systemic vascular tone. Histamine is not a potent modifier of the circulation in the newborn piglet during conditions of normoxaemia or hypoxaemia.

  4. Histamine concentration is involved in canine valvular disease

    Directory of Open Access Journals (Sweden)

    Mitsuhiro Isaka

    2014-05-01

    Full Text Available It has been known since many years that there are histamine receptors (H in the heart. Histamines display chronotropic and inotropic activity, cardiovascular diseases, and are thought to be a systemic inflammatory disease. During heart failure, the histamine concentration is elevated. In addition, H2 blockers prolonged the survival period for human patients with heart failure. The aim of this study was to evaluate whether blood concentration of histamine is associated with canine valvular disease (CVD. The histamine concentrations of dogs with CVD are significantly higher than those of healthy dogs. The histamine concentration gradually increases during CVD and is highly correlated with the grade of heart murmur. In conclusion, the histamine concentration was higher in the population of dogs with CVD compared with the healthy controls. Although the etiopathogenesis of CVD is complex and incompletely understood, it likely involves histamine. Ultimately additional studies are required to determine whether histamine blockers might be useful for the management of dogs with cardiac valvular disease.

  5. ROSA/LSTF Tests and RELAP5 Posttest Analyses for PWR Safety System Using Steam Generator Secondary-Side Depressurization against Effects of Release of Nitrogen Gas Dissolved in Accumulator Water

    Directory of Open Access Journals (Sweden)

    Takeshi Takeda

    2016-01-01

    Full Text Available Two tests related to a new safety system for a pressurized water reactor were performed with the ROSA/LSTF (rig of safety assessment/large scale test facility. The tests simulated cold leg small-break loss-of-coolant accidents with 2-inch diameter break using an early steam generator (SG secondary-side depressurization with or without release of nitrogen gas dissolved in accumulator (ACC water. The SG depressurization was initiated by fully opening the depressurization valves in both SGs immediately after a safety injection signal. The pressure difference between the primary and SG secondary sides after the actuation of ACC system was larger in the test with the dissolved gas release than that in the test without the dissolved gas release. No core uncovery and heatup took place because of the ACC coolant injection and two-phase natural circulation. Long-term core cooling was ensured by the actuation of low-pressure injection system. The RELAP5 code predicted most of the overall trends of the major thermal-hydraulic responses after adjusting a break discharge coefficient for two-phase discharge flow under the assumption of releasing all the dissolved gas at the vessel upper plenum.

  6. The carcinine transporter CarT is required in Drosophila photoreceptor neurons to sustain histamine recycling

    Science.gov (United States)

    Stenesen, Drew; Moehlman, Andrew T; Krämer, Helmut

    2015-01-01

    Synaptic transmission from Drosophila photoreceptors to lamina neurons requires recycling of histamine neurotransmitter. Synaptic histamine is cleared by uptake into glia and conversion into carcinine, which functions as transport metabolite. How carcinine is transported from glia to photoreceptor neurons remains unclear. In a targeted RNAi screen for genes involved in this pathway, we identified carT, which encodes a member of the SLC22A transporter family. CarT expression in photoreceptors is necessary and sufficient for fly vision and behavior. Carcinine accumulates in the lamina of carT flies. Wild-type levels are restored by photoreceptor-specific expression of CarT, and endogenous tagging suggests CarT localizes to synaptic endings. Heterologous expression of CarT in S2 cells is sufficient for carcinine uptake, demonstrating the ability of CarT to utilize carcinine as a transport substrate. Together, our results demonstrate that CarT transports the histamine metabolite carcinine into photoreceptor neurons, thus contributing an essential step to the histamine–carcinine cycle. DOI: http://dx.doi.org/10.7554/eLife.10972.001 PMID:26653853

  7. Histamine H3-receptor inverse agonists as novel antipsychotics.

    Science.gov (United States)

    Ito, Chihiro

    2009-06-01

    Schizophrenia (SZ) that is resistant to treatment with dopamine (DA) D2 antagonists may involve changes other than those in the dopaminergic system. Recently, histamine (HA), which regulates arousal and cognitive functions, has been suggested to act as a neurotransmitter in the central nervous system. Four HA receptors-H1, H2, H3, and H4-have been identified. Our recent basic and clinical studies revealed that brain HA improved the symptoms of SZ. The H3 receptor is primarily localized in the central nervous system, and it acts not only as a presynaptic autoreceptor that modulates the HA release but also as a presynaptic heteroreceptor that regulates the release of other neurotransmitters such as monoamines and amino acids. H3-receptor inverse agonists have been considered to improve cognitive functions. Many atypical antipsychotics are H3-receptor antagonists. Imidazole-containing H3-receptor inverse agonists inhibit not only cytochrome P450 but also hERG potassium channels (encoded by the human ether-a-go-go-related gene). Several imidazole H3-receptor inverse agonists also have high affinity for H4 receptors, which are expressed at high levels in mast cells and leukocytes. Clozapine is an H4-receptor agonist; this agonist activity may be related to the serious side effect of agranulocytosis caused by clozapine. Therefore, selective non-imidazole H3-receptor inverse agonists can be considered as novel antipsychotics that may improve refractory SZ.

  8. Glutamatergic regulation of brain histamine neurons: In vivo microdialysis and electrophysiology studies in the rat.

    Science.gov (United States)

    Fell, Matthew J; Flik, Gunnar; Dijkman, Ulrike; Folgering, Joost H A; Perry, Kenneth W; Johnson, Bryan J; Westerink, Ben H C; Svensson, Kjell A

    2015-12-01

    The interactions between the glutamatergic and the histaminergic systems in the brain are not fully understood. Here we studied histamine release in the medial prefrontal cortex and the posterior hypothalamus-tuberomamillary nucleus (PH-TMN) using in vivo microdialysis and electrophysiological recordings of histaminergc neurons in the PH-TMN in vivo to further address the mechanistic details of these interactions. We demonstrated that histaminergic activity was regulated by group II metabotropic glutamate receptors (mGluR 2 and 3) using systemic dosing with mGluR 2/3 agonist and antagonists and an mGluR 2 positive allosteric modulator. These interactions likely occur via direct modulation of glutamate release in the PH-TMN. The importance of circadian rhythm for histamine release was also shown using microdialysis studies with mGluR 2/3 compounds under light and dark conditions. Based on histamine release studies with NMDA and ketamine, we propose the existence of two sub-populations of NMDA receptors where one subtype is located on histaminergic cell bodies in the PH-TMN and the second on GABA-ergic neurons projecting to the PH-TMN. These subpopulations could be distinguished based on function, notably opposing actions were seen on histamine release in the medial prefrontal cortex of the rat. In summary, this paper provides evidence that the histaminergic system is closely regulated by glutamate neurons in multiple ways. In addition, this interaction depends to a great extent on the activity state of the subject.

  9. Review of prediction of myocardial ischemia by histamine%组胺预测心肌缺血研究进展

    Institute of Scientific and Technical Information of China (English)

    雷芾华; 张玲; 侯月梅

    2014-01-01

    不稳定粥样斑块内的肥大细胞释放组胺促进动脉粥样硬化进展及心肌缺血。组胺释放增加,引起心动过速、血压升高和室性心律失常。冠状动脉病变患者血组胺含量明显高于正常。本文就组胺的生物学特性及其预测心肌缺血的进展综述,以期全面理解组胺与心肌缺血的关系。%Histamine released by mast cells in vulnerable coronary plaque promoted the progress of atherosclerosis and myocardia ischemia. The increase of histamine release can cause tachycardia, elevate blood pressure and cause ventricular arrhythmia. The level of blood histamine from patients with coronary artery disease was higher than normal people. This article reviewed the biological characteristics of histamine and the progress on prediction of myocardial ischemia, so as to fully understand the relationship between histamine and myocardial ischemia.

  10. Cross state-dependent retrieval between histamine and lithium.

    Science.gov (United States)

    Zarrindast, Mohammad-Reza; Fazli-Tabaei, Soheila; Khalilzadeh, Azita; Farahmanfar, Maryam; Yahyavi, Seyed-Hossein

    2005-09-15

    Histamine and lithium state-dependent (StD) retrieval of passive avoidance task and their interactions was examined in mice. The pre-training or pre-test intracerebroventricular (i.c.v.) injection of histamine (20 microg/mouse) impaired retrieval when it was tested 24 h later. In the animals, in which retrieval was impaired due to histamine pre-training administration, pre-test administration of histamine, with the same dose, restored retrieval. The H1 blocker, pyrilamine (20 microg/mouse, i.c.v.), but not the H(2) blocker; ranitidine prevented the restoration of retrieval by pre-test histamine. The pre-training (5 and 10 mg/kg) or pre-test (5 mg/kg) injection of lithium also impaired retrieval, when it was tested 24 h later. In the animals that received lithium (5 mg/kg) or histamine (20 microg/mouse) as pre-training treatment, administration of histamine, clobenpropit or lithium, respectively, resulted in restoration of memory retrieval. Neither pyrilamine nor ranitidine prevented the restoration of retrieval by pre-test lithium. In conclusion, histamine or lithium can induce state-dependent retrieval and a cross-StD exists between these drugs, which may be mediated through the inositol pathway.

  11. 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

  12. Histamine and histamine receptors in Tourette syndrome and other neuropsychiatric conditions.

    Science.gov (United States)

    Rapanelli, Maximiliano; Pittenger, Christopher

    2016-07-01

    The potential contributions of dysregulation of the brain's histaminergic modulatory system to neuropsychiatric disease, and the potential of histamine-targeting medications as therapeutic agents, are gradually coming into focus. The H3R receptor, which is expressed primarily in the central nervous system, is a promising pharmacotherapeutic target. Recent evidence for a contribution of histamine dysregulation to Tourette syndrome and tic disorders is particularly strong; although specific mutations in histamine-associated genes are rare, they have led to informative studies in animal models that may pave the way for therapeutic advances. A controlled study of an H3R antagonist in Tourette syndrome is ongoing. Preclinical studies of H3R antagonists in schizophrenia, attention deficit disorder, and narcolepsy have all shown promise. Recently reported controlled studies have been disappointing in schizophrenia and attention deficit disorder, but the H3R antagonist pitolisant shows promise in the treatment of narcolepsy and excessive daytime sleepiness and is currently under regulatory review for these conditions. This article is part of the Special Issue entitled 'Histamine Receptors'.

  13. Histamine homologues discriminating between two functional H3 receptor assays. Evidence for H3 receptor heterogeneity?.

    Science.gov (United States)

    Leurs, R; Kathmann, M; Vollinga, R C; Menge, W M; Schlicker, E; Timmerman, H

    1996-03-01

    We studied several histamine homologues as potential ligands for the histamine H3 receptor in two binding assays ([125l]iodophenpropit and N alpha-[3H]methylhistamine binding to rat brain cortex membranes) and two functional H3 receptor models (inhibition of the neurogenic contraction in the guinea pig jejunum and of [3H]noradrenaline release in mouse brain cortex slices). The histamine homologues acted all as competitive H3 antagonists at the guinea pig jejunum. The potency in this model and/or the affinity for N alpha-[3H]methylhistamine binding was higher for the butylene (pA2 = 7.7; pKi = 9.4) and pentylene homologue (impentamine, pA2 = 8.4; pKi = 9.1) than for the propylene, hexylene and octylene homologues (pA2 = 5.9-7.8; pKi = 6.1-7.6). In the mouse brain cortex the propylene, butylene and pentylene homologues acted as partial agonists (alpha = 0.3-0.6) and the hexylene and octylene homologues acted as antagonists. [125I]Iodophenpropit binding was displaced monophasically by the propylene, hexylene and octylene homologues and biphasically by the butylene and pentylene homologues. Biphasic displacement curves were converted to monophasic ones by 10 microM guanosine-5'-O-(3-thiotriphosphate. In conclusion, the homologue of histamine with five methylene groups is a more potent H3 receptor antagonist in the guinea pig jejunum than the other homologues tested. Furthermore, the propylene, butylene and pentylene homologues can discriminate between the two functional H3 receptor models in the guinea pig jejunum and mouse brain. These data are discussed in relation to the efficiency of receptor coupling and receptor heterogeneity.

  14. Quantitative analysis of histidine decarboxylase gene (hdcA) transcription and histamine production by Streptococcus thermophilus PRI60 under conditions relevant to cheese making.

    Science.gov (United States)

    Rossi, Franca; Gardini, Fausto; Rizzotti, Lucia; La Gioia, Federica; Tabanelli, Giulia; Torriani, Sandra

    2011-04-01

    This study evaluated the influence of parameters relevant for cheese making on histamine formation by Streptococcus thermophilus. Strains possessing a histidine decarboxylase (hdcA) gene represented 6% of the dairy isolates screened. The most histaminogenic, S. thermophilus PRI60, exhibited in skim milk a high basal level of expression of hdcA, upregulation in the presence of free histidine and salt, and repression after thermization. HdcA activity persisted in cell extracts, indicating that histamine might accumulate after cell lysis in cheese.

  15. Quantitative Analysis of Histidine Decarboxylase Gene (hdcA) Transcription and Histamine Production by Streptococcus thermophilus PRI60 under Conditions Relevant to Cheese Making▿†

    Science.gov (United States)

    Rossi, Franca; Gardini, Fausto; Rizzotti, Lucia; La Gioia, Federica; Tabanelli, Giulia; Torriani, Sandra

    2011-01-01

    This study evaluated the influence of parameters relevant for cheese making on histamine formation by Streptococcus thermophilus. Strains possessing a histidine decarboxylase (hdcA) gene represented 6% of the dairy isolates screened. The most histaminogenic, S. thermophilus PRI60, exhibited in skim milk a high basal level of expression of hdcA, upregulation in the presence of free histidine and salt, and repression after thermization. HdcA activity persisted in cell extracts, indicating that histamine might accumulate after cell lysis in cheese. PMID:21378060

  16. Histidine suppresses food intake through its conversion into neuronal histamine.

    Science.gov (United States)

    Yoshimatsu, Hironobu; Chiba, Seiichi; Tajima, Daisuke; Akehi, Yuko; Sakata, Toshiie

    2002-01-01

    Hypothalamic neuronal histamine has been shown to regulate feeding behavior and energy metabolism as a target of leptin action in the brain. The present study aimed to examine the involvement of L-histidine, a precursor of neuronal histamine, in the regulation of feeding behavior in rats. Intraperitoneal (ip) injection of L-histidine at doses of 0.35 and 0.70 mmol/kg body weight significantly decreased the 24-hr cumulative food and water intakes compared to phosphate buffered saline injected controls (P intracerebroventricular infusion of histidine at doses of 0.5, 1.0, and 2.0 micromol/rat (P histamine and attenuated the suppressive effect of histidine on food intake from 64.2% to 88.1% of the controls (P Administration of 0.35 mmol/kg histidine ip increased the concentration of hypothalamic neuronal histamine compared with the controls (P administration compared with the controls (P histamine in the hypothalamus.

  17. Histamine poisoning and control measures in fish and fishery products

    Directory of Open Access Journals (Sweden)

    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.

  18. Corrosion studies with high burnup light water reactor fuel. Release of nuclides into simulated groundwater during accumulated contact time of up to two years

    Energy Technology Data Exchange (ETDEWEB)

    Zwicky, Hans-Urs (Zwicky Consulting GmbH, Remigen (Switzerland)); Low, Jeanett; Ekeroth, Ella (Studsvik Nuclear AB, Nykoeping (Sweden))

    2011-03-15

    period, water samples are taken for different analyses and for pH and carbonate determination. The fuel sample is placed in a new flask with fresh synthetic groundwater for the next contact period. Release fractions are calculated by dividing the total amount of a nuclide of concern in the analysed solution by the total amount in the corroded fuel sample. Cumulative release fractions are the sum of release fractions up to a certain cumulative contact time. Release rates are calculated by dividing release fractions by the length of the contact period of concern. Caesium and rubidium were released to a significantly larger extent in the high burnup samples, compared to the Series 11 experiments. This is probably more a consequence of different operating conditions than of burnup

  19. The histamine H3 receptor: an attractive target for the treatment of cognitive disorders.

    Science.gov (United States)

    Esbenshade, T A; Browman, K E; Bitner, R S; Strakhova, M; Cowart, M D; Brioni, J D

    2008-07-01

    The histamine H3 receptor, first described in 1983 as a histamine autoreceptor and later shown to also function as a heteroreceptor that regulates the release of other neurotransmitters, has been the focus of research by numerous laboratories as it represents an attractive drug target for a number of indications including cognition. The purpose of this review is to acquaint the reader with the current understanding of H3 receptor localization and function as a modulator of neurotransmitter release and its effects on cognitive processes, as well as to provide an update on selected H3 antagonists in various states of preclinical and clinical advancement. Blockade of centrally localized H3 receptors by selective H3 receptor antagonists has been shown to enhance the release of neurotransmitters such as histamine, ACh, dopamine and norepinephrine, among others, which play important roles in cognitive processes. The cognitive-enhancing effects of H3 antagonists across multiple cognitive domains in a wide number of preclinical cognition models also bolster confidence in this therapeutic approach for the treatment of attention deficit hyperactivity disorder, Alzheimer's disease and schizophrenia. However, although a number of clinical studies examining the efficacy of H3 receptor antagonists for a variety of cognitive disorders are currently underway, no clinical proof of concept for an H3 receptor antagonist has been reported to date. The discovery of effective H3 antagonists as therapeutic agents for the novel treatment of cognitive disorders will only be accomplished through continued research efforts that further our insights into the functions of the H3 receptor.

  20. Genetic Analysis of Histamine Signaling in Larval Zebrafish Sleep

    Science.gov (United States)

    Oikonomou, Grigorios

    2017-01-01

    Abstract Pharmacological studies in mammals and zebrafish suggest that histamine plays an important role in promoting arousal. However, genetic studies using rodents with disrupted histamine synthesis or signaling have revealed only subtle or no sleep/wake phenotypes. Studies of histamine function in mammalian arousal are complicated by its production in cells of the immune system and its roles in humoral and cellular immunity, which can have profound effects on sleep/wake states. To avoid this potential confound, we used genetics to explore the role of histamine in regulating sleep in zebrafish, a diurnal vertebrate in which histamine production is restricted to neurons in the brain. Similar to rodent genetic studies, we found that zebrafish that lack histamine due to mutation of histidine decarboxylase (hdc) exhibit largely normal sleep/wake behaviors. Zebrafish containing predicted null mutations in several histamine receptors also lack robust sleep/wake phenotypes, although we are unable to verify that these mutants are completely nonfunctional. Consistent with some rodent studies, we found that arousal induced by overexpression of the neuropeptide hypocretin (Hcrt) or by stimulation of hcrt-expressing neurons is not blocked in hdc or hrh1 mutants. We also found that the number of hcrt-expressing or histaminergic neurons is unaffected in animals that lack histamine or Hcrt signaling, respectively. Thus, while acute pharmacological manipulation of histamine signaling has been shown to have profound effects on zebrafish and mammalian sleep, our results suggest that chronic loss of histamine signaling due to genetic mutations has only subtle effects on sleep in zebrafish, similar to rodents. PMID:28275716

  1. An inverse agonist of the histamine H(3) receptor improves wakefulness in narcolepsy: studies in orexin-/- mice and patients.

    OpenAIRE

    Lin, Jian Sheng; Dauvilliers, Yves; Arnulf, Isabelle; Bastuji, Hélène; Anaclet, Christelle; Parmentier, Régis; Kocher, Laurence; Yanagisawa, Masashi; Lehert, Philippe; Ligneau, Xavier; Perrin, David; Robert, Philippe; Roux, Michel; Lecomte, Jeanne-Marie; Schwartz, Jean-Charles

    2008-01-01

    International audience; Narcolepsy is characterized by excessive daytime sleepiness (EDS), cataplexy, direct onsets of rapid eye movement (REM) sleep from wakefulness (DREMs) and deficiency of orexins, neuropeptides that promote wakefulness largely via activation of histamine (HA) pathways. The hypothesis that the orexin defect can be circumvented by enhancing HA release was explored in narcoleptic mice and patients using tiprolisant, an inverse H(3)-receptor agonist. In narcoleptic orexin(-/...

  2. Effect of Soil Moisture on Release of Low-MolecularWeight Organic Acids in Root Exudates and the Accumulation of Iron in Root Apoplasm of Peanut

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    A three-compartments rhizobox was designed and used to study the low-molecular-weight organic acids in root exudates and the root apoplastic iron of "lime-induced chlorosis" peanut grown on a calcareous soil in relation to different soil moisture conditions. Results showed that chlorosis of peanuts developed under condition of high soil moisture level (250 g kg-1), while peanuts grew well and chlorosis did not develop when soil moisture was managed to a normal level (150 g kg-1). The malic acid, maleic acid and succinic acid contents of chlorotic peanut increased by 108.723, 0.029 and 22.446μg cm-2, respectively,compared with healthy peanuts. The content of citric acid and fumaric acid also increased in root exudates of chlorotic peanuts. On Days 28 and 42 of peanut growth, the accumulation of root apoplastic iron in chlorotic peanuts was higher than that of healthy peanuts. From Day 28 to Day 42, the mobilization percentages of chlorotic peanuts and healthy peanuts to root apoplastic iron were almost the same, being 52.4% and 52.8%,respectively, indicating that the chlorosis might be caused by the inactivation of iron within peanut plant grown on a calcareous soil under high soil moisture conditions.

  3. Interaction of clozapine with the histamine H3 receptor in rat brain.

    OpenAIRE

    RODRIGUES, A. de A.; Jansen, F.P.; Leurs, R.; Timmerman, H.; Prell, G. D.

    1995-01-01

    We examined possible interactions between neuroleptics and the histamine H3 receptor and found an interaction of clozapine with this receptor. In competition binding experiments, using the H3 antagonist, [125I]-iodophenpropit, we observed a Ki of 236 +/- 87 nM. Functionally, clozapine was studied on the H3-mediated inhibition of [3H]-5-hydroxytryptamine ([3H]-5-HT) release from rat brain cortex slices. Clozapine acts as an antagonist with an apparent KB value of 79.5 nM.

  4. The gastric acid secretagogue gastrin-releasing peptide and the inhibitor oxyntomodulin do not exert their effect directly on the parietal cell in the rat

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier; Holst, J J

    1988-01-01

    Previous studies suggested that gastrin-releasing peptide (a neuropeptide found in rat oxyntic mucosa) and oxyntomodulin (a glucagon-containing peptide of mammalian gut) could directly affect the acid secretion of the parietal cells. We therefore studied their effect on gastric acid production in...... and histamine-stimulated parietal cells confirmed that the cells retained the normal morphology of intracellular organelles and that the cells responded to physiological stimulation by marked expansion of the intracellular canaliculi.......Previous studies suggested that gastrin-releasing peptide (a neuropeptide found in rat oxyntic mucosa) and oxyntomodulin (a glucagon-containing peptide of mammalian gut) could directly affect the acid secretion of the parietal cells. We therefore studied their effect on gastric acid production...... in vitro by measuring [14C]-aminopyrine accumulation, a reliable index of H+ generation, in isolated rat parietal cells. However, neither gastrin-releasing peptide nor oxyntomodulin influenced basal acid secretion or histamine-stimulated gastric acid secretion. Electron-microscopic studies of unstimulated...

  5. In vivo demonstration of H3-histaminergic inhibition of cardiac sympathetic stimulation by R-α-methyl-histamine and its prodrug BP 2.94 in the dog

    OpenAIRE

    Mazenot, Catherine; Ribuot, Christophe; Durand, Andrée; Joulin, Yves; Demenge, Pierre; Godin-Ribuot, Diane

    1999-01-01

    The aim of this study was to investigate whether histamine H3-receptor agonists could inhibit the effects of cardiac sympathetic nerve stimulation in the dog.Catecholamine release by the heart and the associated variation of haemodynamic parameters were measured after electrical stimulation of the right cardiac sympathetic nerves (1–4 Hz, 10 V, 10 ms) in the anaesthetized dog treated with R-α-methyl-histamine (R-HA) and its prodrug BP 2.94 (BP).Cardiac sympathetic stimulation induced a noradr...

  6. Effects of antidepressants and antihistaminics on catalepsy induced by intracerebroventricular administration of histamine in mice.

    Science.gov (United States)

    Onodera, K

    1991-01-01

    The intracerebroventricular (icv) administration of histamine but not N-telemethylhistamine and 1-methyl-4-imidazole acetic acid induced catalepsy in mice. Histamine H1-receptor blockers such as cyproheptadine, mepyramine and diphenhydramine reduced histamine-induced catalepsy. However, astemizole which is known to be without central effects, did not reduce histamine-induced catalepsy. The icv pretreatment with histamine H2-receptor blockers, such as metiamide and cimetidine, also had no effect. Moreover, various antidepressants, both imipramine- and atypical-type drugs antagonized histamine-induced catalepsy to various degrees in this experiment. Thus, the induction of catalepsy by icv administration of histamine was mediated through histamine H1-receptors, and suggested that antidepressants reduced histamine-induced catalepsy via this mechanism. Histamine-induced catalepsy is a possible new animal model of depression which can also be used for evaluation of atypical antidepressants.

  7. 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...... experiments revealed that histamine adsorbed onto a solid-phase could bind the antiserum. However, neither free histamine nor histamine coupled to unrelated carriers could inhibit the binding of antiserum to the solid-phase histamine. Cross-reactivity was demonstrated between HSA and solid-phase bound...... histamine, as the immunoradiometric assay was inhibited by HSA. This unexpected cross-reactivity was established, as a commercially available antiserum with specificity to HSA without histamine also bound to the solid-phase bound histamine. It is suggested that preparations of antibodies against histamine...

  8. Involvement of central histamine in amygdaloid kindled seizures in rats.

    Science.gov (United States)

    Kamei, C

    2001-10-15

    The involvement of central histamine in amygdaloid kindled seizures in rats was investigated using histamine-related compounds. Histamine contents in the amygdala of electrical stimulation site was significantly decreased after development of amygdaloid kindling. Intracerebroventricular (i.c.v.) injection of histamine resulted in inhibition of amygdaloid kindled seizures. The H(1)-agonists 2-methylhistamine and 2-thiazolylethylamine also inhibited amygdaloid kindled seizures. In addition, intraperitoneal (i.p.) injection of histidine and metoprine inhibited amygdaloid kindled seizures at doses that caused increases in histamine contents of the brain. H(1)-antagonists (diphenhydramine and chlorpheniramine) attenuated histamine (i.c.v.)-induced inhibition of amygdaloid kindled seizures, however, no significant antagonism was observed with H(2)-antagonists (cimetidine, ranitidine or zolantidine). Intracerebroventricular injection of H(3)-antagonists (thioperamide and AQ 0145) resulted in a dose-related inhibition of amygdaloid kindled seizures. The same findings were observed when thioperamide and clobenpropit were injected i.p. The effects of thioperamide (i.p.) and AQ 0145 (i.p.) were inhibited by an H(3)-agonist [(R)-alpha-methylhistamine] and H(1)-antagonists (diphenhydramine and chlorpheniramine). On the other hand, H(2)-antagonists (cimetidine and ranitidine) showed no antagonistic effects. These findings suggested that a histaminergic mechanism plays an important role in suppressing amygdaloid kindled seizures through histamine H(1)-receptors.

  9. [Role of central histamine in amygdaloid kindled seizures].

    Science.gov (United States)

    Kamei, C; Okuma, C

    2001-05-01

    The role of central histamine in amygdaloid kindled seizures in rats was studied. Histamine content in the amygdala was significantly decreased after development of amygdaloid kindling. Intracerebroventricular (i.c.v.) injection of histamine resulted in inhibition of amygdaloid kindled seizures. The H1-agonists 2-methylhistamine and 2-thiazolylethylamine also inhibited amygdaloid kindled seizures. In addition, intraperitoneal (i.p.) injection of histidine and metoprine inhibited amygdaloid kindled seizures at doses that caused increases in histamine contents of the brain. H1-antagonists (diphenhydramine and chlorpheniramine) attenuated histamine- or histidine-induced inhibition of amygdaloid kindled seizures. Both i.c.v. and i.p. injections of H3-antagonists (thioperamide, AQ0145 and clobenpropit) resulted in a dose-related inhibition of amygdaloid kindled seizures. The effects of thioperamide and AQ0145 were inhibited by an H3-agonist (R)-alpha-methylhistamine and H1-antagonists. On the other hand, H2-antagonists showed no antagonistic effect. GABAmimetic drugs, diazepam, sodium valproate and muscimol potentiated the effect of clobenpropit. Bicuculline caused significant antagonism of the inhibition of amygdaloid kindled seizures induced by clobenpropit. These findings suggested that a histaminergic mechanism plays an important role in suppressing amygdaloid kindled seizures through histamine H1-receptors. In addition, an inhibition of amygdaloid kindled seizures induced by histamine is closely related with the action of GABA.

  10. Histamine Potentiates Cyclosomatostatin-Induced Catalepsy in Old Rats

    Directory of Open Access Journals (Sweden)

    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.

  11. 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.

  12. Itching for answers: how histamine relaxes lymphatic vessels.

    Science.gov (United States)

    Scallan, Joshua P; Davis, Michael J

    2014-10-01

    In the current issue of Microcirculation, studies by Kurtz et al. and Nizamutdinova et al. together provide new evidence supporting a role for histamine as an endothelial-derived molecule that inhibits lymphatic muscle contraction. In particular, Nizamutdinova et al. show that the effects of flow-induced shear stress on lymphatic endothelium are mediated by both nitric oxide and histamine, since only blockade of both prevents contraction strength and frequency from being altered by flow. Separately, Kurtz et al. used confocal microscopy to determine a preferential expression of histamine receptors on the lymphatic endothelium and demonstrated that histamine applied to spontaneously contracting collecting lymphatics inhibits contractions. Previous studies disagreed on whether histamine stimulates or inhibits lymphatic contractions, but also used differing concentrations, species, and preparations. Together these new reports shed light on how histamine acts within the lymphatic vasculature, but also raise important questions about the cell type on which histamine exerts its effects and the signaling pathways involved. This editorial briefly discusses the contribution of each study and its relevance to lymphatic biology.

  13. Molecularly imprinted polymers for histamine recognition in aqueous environment.

    Science.gov (United States)

    Trikka, Foteini A; Yoshimatsu, Keiichi; Ye, Lei; Kyriakidis, Dimitrios A

    2012-11-01

    Molecularly imprinted polymers (MIP) for histamine using methacrylic acid were developed and recognition mechanisms were thoroughly characterized for the first time in this study. The binding affinity of imprinted polymer with structurally related compounds was studied in organic and aqueous media, at various conditions. In organic media, MIP was found to bind histamine two and six times more than ranitidine and fluoxetine, respectively, whereas higher selectivity was observed in the case of dimentidene or disodium cromoglycate. The specific binding sites of MIP recognized histamine over L-histidine in aqueous conditions, while higher affinity for histamine compared to ranitidine, disodium cromoglycate, putrescine and to a putrescine analogue was observed. A combination of NMR and UV spectroscopy analyses for investigation of imprinting and recognition properties revealed that strong specific interactions between the functional monomer and histamine in the prepolymerization and in the aqueous solutions were probably responsible for histamine recognition. The preparation of histamine MIPs and elucidation of imprinting and recognition mechanism may serve as useful insight for future application of MIPs.

  14. Donepezil, an acetylcholine esterase inhibitor, and ABT-239, a histamine H3 receptor antagonist/inverse agonist, require the integrity of brain histamine system to exert biochemical and procognitive effects in the mouse.

    Science.gov (United States)

    Provensi, Gustavo; Costa, Alessia; Passani, M Beatrice; Blandina, Patrizio

    2016-10-01

    Histaminergic H3 receptors (H3R) antagonists enhance cognition in preclinical models and modulate neurotransmission, in particular acetylcholine (ACh) release in the cortex and hippocampus, two brain areas involved in memory processing. The cognitive deficits seen in aging and Alzheimer's disease have been associated with brain cholinergic deficits. Donepezil is one of the acetylcholinesterase (AChE) inhibitor approved for use across the full spectrum of these cognitive disorders. We addressed the question if H3R antagonists and donepezil require an intact histamine neuronal system to exert their procognitive effects. The effect of the H3R antagonist ABT-239 and donepezil were evaluated in the object recognition test (ORT), and on the level of glycogen synthase kinase 3 beta (GSK-3β) phosphorylation in normal and histamine-depleted mice. Systemic administration of ABT-239 or donepezil ameliorated the cognitive performance in the ORT. However, these compounds were ineffective in either genetically (histidine decarboxylase knock-out, HDC-KO) or pharmacologically, by means of intracerebroventricular (i.c.v.) injections of the HDC irreversible inhibitor a-fluoromethylhistidine (a-FMHis), histamine-deficient mice. Western blot analysis revealed that ABT-239 or donepezil systemic treatments increased GSK-3β phosphorylation in cortical and hippocampal homogenates of normal, but not of histamine-depleted mice. Furthermore, administration of the PI3K inhibitor LY294002 that blocks GSK-3β phosphorylation, prevented the procognitive effects of both drugs in normal mice. Our results indicate that both donepezil and ABT-239 require the integrity of the brain histaminergic system to exert their procognitive effects and strongly suggest that impairments of PI3K/AKT/GSK-3β intracellular pathway activation is responsible for the inefficacy of both drugs in histamine-deficient animals.

  15. Central interaction between physostigmine and histamine during yawning in rats.

    Science.gov (United States)

    Tamaddonfard, Esmaeal; Soraya, Hamid; Hamzeh-Gooshchi, Nasrin

    2008-01-01

    In this study, the effects of intraperitoneal (ip) injection of physostigmine, subcutaneous (sc) injection of atropine, and intracerebroventricular (icv) injections of histamine, chlorpheniramine (H(1)-receptor antagonist), and ranitidine (H(2)-receptor antagonist) in separate and combined treatments were investigated during yawning in rats. Physostigmine at a dose of 0.25 mg/kg produced the highest number of yawns. Atropine, used alone, was without effect, but physostigmine (0.25 mg/kg, ip)-induced yawning was blocked by pretreatment with atropine (1 mg/kg, sc). Histamine at the doses of 10, 20 and 40 microg produced yawning. Chlorpheniramine and ranitidine, used alone, had no effect, whereas pretreatments with chlorpheniramine and ranitidine at the same dose of 80 microg prevented histamine (40 microg, icv)-induced yawning. The suppressive effect of chlorpheniramine was more than that of ranitidine. Histamine (10 and 40 microg, icv) enhanced, whereas chlorpheniramine and ranitidine at the same dose of 80 microg suppressed, physostigmine (0.25 mg/kg, ip)-induced yawning. Atropine (1 mg/kg, sc) not only suppressed histamine-induced yawning, but also enhanced the inhibitory effect of chlorpheniramine, but not of ranitidine on yawning induced by histamine. These results indicate that muscarinic receptors mediate yawning induced by physostigmine. Histamine central H(1), and to a lesser extent H(2) receptors, may be involved in histamine-induced yawning. Cholinergic muscarinic receptors, as well as histaminergic H(1) and to a lesser extent H(2) receptors, may lso be involved in the interaction between brain acetylcholine and histamine.

  16. Cardiovascular reflexes evoked by histamine stimulation of the stomach.

    Science.gov (United States)

    Stebbins, C L; Theodossy, S J; Longhurst, J C

    1991-04-01

    This study examined the potential for histamine to cause cardiovascular reflexes when applied to the serosal or mucosal surface of the stomach. Thus, in chloralose-anesthetized cats, histamine was applied to the serosal surface of the stomach in concentrations ranging from 0.5 to 1,000 micrograms/ml. This resulted in graded increases in mean arterial pressure (MAP), maximal left ventricular pressure over time (dP/dt), and heart rate ranging from 9 +/- 4 to 30 +/- 3 mmHg, 450 +/- 103 to 1,710 +/- 610 mmHg/s, and 2 +/- 1 to 13 +/- 4 beats/min, respectively. Histamine stimulation of the gastric serosa evoked a greater pressor response than that observed when the same concentration of histamine (100 micrograms/ml) was applied to the gastric mucosa (43 +/- 7 vs. 13 +/- 3 mmHg, respectively). In six cats, celiac ganglionectomy abolished the previously observed cardiovascular response to histamine stimulation of the serosal surface of the stomach. When the gastric serosa was treated with the H1-receptor antagonist diphenhydramine (1 mg/ml) (n = 5), the cardiovascular response to histamine was abolished. In five other cats, administration of the H2-antagonist ranitidine (1 mg/ml) had no effect on the histamine-induced responses. When indomethacin (2-5 mg/ml), was applied to the serosal surface of the stomach (n = 6), histamine-induced increases in MAP and dP/dt were attenuated. However, application of PGE2 (1 microgram/ml) restored these two responses. These results suggest that histamine stimulates H1-receptors in the gastric wall to cause reflex cardiovascular responses that are dependent, in part, on the local production of prostaglandins.

  17. Ca2+ influx through L-type Ca2+ channels and Ca2+-induced Ca2+ release regulate cAMP accumulation and Epac1-dependent ERK 1/2 activation in INS-1 cells.

    Science.gov (United States)

    Pratt, Evan P S; Salyer, Amy E; Guerra, Marcy L; Hockerman, Gregory H

    2016-01-05

    We previously reported that INS-1 cells expressing the intracellular II-III loop of the L-type Ca(2+) channel Cav1.2 (Cav1.2/II-III cells) are deficient in Ca(2+)-induced Ca(2+) release (CICR). Here we show that glucose-stimulated ERK 1/2 phosphorylation (GSEP) is slowed and reduced in Cav1.2/II-III cells compared to INS-1 cells. This parallels a decrease in glucose-stimulated cAMP accumulation (GS-cAMP) in Cav1.2/II-III cells. Influx of Ca(2+) via L-type Ca(2+) channels and CICR play roles in both GSEP and GS-cAMP in INS-1 cells since both are inhibited by nicardipine or ryanodine. Further, the Epac1-selective inhibitor CE3F4 abolishes glucose-stimulated ERK activation in INS-1 cells, as measured using the FRET-based sensor EKAR. The non-selective Epac antagonist ESI-09 but not the Epac2-selective antagonist ESI-05 nor the PKA antagonist Rp-cAMPs inhibits GSEP in both INS-1 and Cav1.2/II-III cells. We conclude that L-type Ca(2+) channel-dependent cAMP accumulation, that's amplified by CICR, activates Epac1 and drives GSEP in INS-1 cells.

  18. 组胺H1受体缺乏改变小鼠脑内组胺含量及昼夜节律%HISTAMINE H1 RECEPTOR DEFICIENCY ALTERS BRAIN HISTAMINE CONTENTS AND CIRCADIAN RHYTHM IN MICE

    Institute of Scientific and Technical Information of China (English)

    洪宗元

    2005-01-01

    在乙谜麻醉下,分别于明时(8:00 a.m.)及暗时(8:00 p.m.)断头处死野生型及组胺H1R基因敲除型小鼠,迅速取出脑组织并分离出皮层、纹状体、海马、下丘脑、丘脑、中脑及脑干等脑区.这些脑组织被制成匀浆并用HPLC荧光检测法测量其组胺含量.结果显示暗时处死时,H1R基因敲除型小鼠海马、丘脑、中脑及脑干中的组胺含量明显低于野生型小鼠.明时处死时,野生型小鼠各脑区组胺含量均较暗时处死显著降低,但这一变化在H1R基因敲除型小鼠中并未观察到.这些表明作为组胺的功能靶,H1R不仅介导组胺的功能,而且调节大脑中组胺含量与释放的昼夜节律.%Under anesthesia by diethyl ether, histamine H1 receptor (H1R) gene knockout (KO) and wild-type (WT) mice were killed by decapitation either at 8:00 p.m. or at 8:00 a.m. The brains were quickly removed out and divided on ice into seven regions: the cortex, striatum, hippocampus, hypothalamus, thalamus, midbrain and medulla. These brain regions were homogenized and the histamine content in the homogenate was determined by HPLC- fluorometry. The results showed that at 8:00 p.m. histamine contents in the hippocampus, thalamus, midbrain, and medulla of DPR-KO mice were significantly decreased compared with WT mice (P<0.05). In WT mice, histamine contents in almost all brain regions were markedly higher at 8:00 p.m. than at 8:00 a.m, whereas the difference was not observed in H1R KO mice. We conclude that as the function target of histamine, H1R not only modulates the function of histamine, but also regulates the histamine content and its synthesizing or releasing rhythm in the mouse brain.

  19. Activation of histamine H3 receptors produces presynaptic inhibition of neurally evoked cat nictitating membrane responses in vivo.

    Science.gov (United States)

    Koss, M C; Hey, J A

    1992-08-01

    This study was undertaken in order to determine the potential role of prejunctional histamine H3 receptors in an in vivo adrenergic model system. Frequency-dependent nictitating membrane responses were elicited by sympathetic nerve stimulation in anesthetized cats. Systemic administration of the selective histamine H3 receptor agonist, (R)-alpha-methylhistamine (R alpha MeHA) produced a dose-related depression of amplitude of the evoked nictitating membrane responses with a threshold of about 10 micrograms/kg and maximal effect (50% depression at the lowest frequency; 0.5 Hz) seen at 100-300 micrograms/kg. Responses obtained with low frequency stimulation were more sensitive to depression by R alpha MeHA than were responses evoked with higher frequencies of stimulation. Larger doses of R alpha MeHA given to the same animals, failed to produce additional inhibition. R alpha MeHA depressed the amplitude of nictitating membrane responses evoked by either pre- or postganglionic nerve stimulation to an equivalent degree. This depressant action of R alpha MeHA was antagonized by pretreatment with the specific histamine H3 antagonist, thioperamide (3 mg/kg), but not by combined pretreatment with histamine H1 and H2 blockers chlorpheniramine (300 micrograms/kg) and cimetidine (5 mg/kg). Intravenous administration of adrenaline (1-30 micrograms/kg) also produced graded nictitating membrane responses that were not altered by subsequent administration of R alpha MeHA. These results suggest that histamine H3 receptors are involved in the modulation of neurally evoked noradrenaline release in the cat nictitating membrane by an inhibitory presynaptic action.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. The osmotically and histamine-induced enhancement of the plasma vasopressin level is diminished by intracerebroventricularly administered orexin in rats.

    Science.gov (United States)

    Kis, Gyöngyi K; Molnár, Andor H; Daruka, Leila; Gardi, János; Rákosi, Kinga; László, Ferenc; László, Ferenc A; Varga, Csaba

    2012-04-01

    The effects of the centrally administered neuropeptides orexin-A on water intake and vasopressin (VP) secretion were studied in male Wistar rats (180-250 g). Different doses (10, 30, and 90 μg/10 μl) of the orexins and the specific orexin receptor-1 (OX(1)) antagonist SB 408124 (30 μg/10 μl) were administered intracerebroventricularly (i.c.v.) under anaesthesia, and the water consumption was measured during 6 h. A plasma VP level elevation was induced by histamine (10 mg/kg) or 2.5% NaCl (10 ml/kg) administered intraperitoneally (i.p.). The plasma VP levels were measured by radioimmunoassay. Increased water consumption was observed after the administration of 30 μg/10 μl orexin-A. There were no changes in basal VP secretion after the administration of different doses of the orexins. A significant increase in plasma VP concentration was detected following histamine administration. After 2.5% NaCl administration, there was a moderate VP level enhancement. Intracerebroventricularly administered orexin-A (30 μg/10 μl) blocked the VP level increase induced by either histamine or 2.5% NaCl administration. The inhibitory effects were prevented by the specific OX(1) receptor antagonist. In conclusion, the orexins increased water consumption. After 30 μg/10 μl orexin-A administration, the polydipsia was more pronounced. The OX(1) receptor antagonist significantly decreased the polydipsia. Histamine or hyperosmotic VP release enhancement was blocked by previously administered orexin. This inhibition was not observed following OX(1) receptor antagonist administration. Our results suggest that the effects of the orexins on water consumption or blockade of the histamine and osmosis-induced VP level increase are mediated by the OX(1) receptor.

  1. Multiple Targeting Approaches on Histamine H3 Receptor Antagonists.

    Science.gov (United States)

    Khanfar, Mohammad A; Affini, Anna; Lutsenko, Kiril; Nikolic, Katarina; Butini, Stefania; Stark, Holger

    2016-01-01

    With the very recent market approval of pitolisant (Wakix®), the interest in clinical applications of novel multifunctional histamine H3 receptor antagonists has clearly increased. Since histamine H3 receptor antagonists in clinical development have been tested for a variety of different indications, the combination of pharmacological properties in one molecule for improved pharmacological effects and reduced unwanted side-effects is rationally based on the increasing knowledge on the complex neurotransmitter regulations. The polypharmacological approaches on histamine H3 receptor antagonists on different G-protein coupled receptors, transporters, enzymes as well as on NO-signaling mechanism are described, supported with some lead structures.

  2. Multiple Targeting Approaches on Histamine H3 Receptor Antagonists

    Directory of Open Access Journals (Sweden)

    Mohammad eKhanfar

    2016-05-01

    Full Text Available With the very recent market approval of pitolisant (Wakix®, the interest in clinical applications of novel multifunctional histamine H3 receptor antagonists has clearly increased. Since histamine H3 receptor antagonists in clinical development have been tested for a variety of different indications, the combination of pharmacological properties in one molecule for improved pharmacological effects and reduced unwanted side-effects is rationally based on the increasing knowledge on the complex neurotransmitter regulations. The polypharmacological approaches on histamine H3 receptor antagonists on different G-protein coupled receptors, transporters, enzymes as well as on NO-signaling mechanism are described, supported with some lead structures.

  3. OCCURANCE OF HISTAMINE IN FISH PRODUCTS ON MARKET

    Directory of Open Access Journals (Sweden)

    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

  4. The histamine H3 receptor: from discovery to clinical trials with pitolisant.

    Science.gov (United States)

    Schwartz, Jean-Charles

    2011-06-01

    The third histamine receptor was discovered in 1983 by a traditional pharmacological approach, consisting of assessing the inhibitory effect of histamine on its own release from depolarized rat brain slices. The same in vitro test was used to design, in 1987, the first highly selective and potent H3-autoreceptor ligands, the antagonist thioperamide and the agonist (R)alphamethylhistamine which enhances and inhibits, respectively, the activity of histaminergic neurons in brain. The use of these research tools was instrumental in establishing the main functions of cerebral histaminergic neurons, namely their role in maintenance of wakefulness, attention, learning and other cognitive processes. In 1990, the cloning of the gene of the H3-receptor, a member of the superfamily of heptahelical receptors coupled to G proteins, paved the way to the demonstration of the high constitutive activity of the receptor, including its native form, and its participation in the tonic control of histamine release; it also facilitated the development of H3-receptor inverse agonist programs in many drug companies. Pitolisant (BF2.649, 1-{3-[3-(4-chlorophenyl)propoxy]propyl}piperidine, hydrochloride) is the first inverse agonist to be introduced in the clinics. Its wake-promotion activity was evidenced in excessive diurnal sleepiness of patients with narcolepsy, Parkinson's disease or Obstructive Sleep Apnea/Hypopnea, in which this activity is characterized by a mean decrease of the Epworth Sleepiness Scale by about five units. The procognitive activity of this novel class of drugs may also find therapeutic applications in dementias, schizophrenia or attention deficit hyperactivity disorder.

  5. Histamine impairs midbrain dopaminergic development in vivo by activating histamine type 1 receptors

    OpenAIRE

    Escobedo-Ávila, Itzel; Vargas-Romero, Fernanda; Molina-Hernández, Anayansi; López-González, Rodrigo; Cortés, Daniel; De Carlos, Juan A.; Velasco, Iván

    2014-01-01

    Background Histamine (HA) regulates the sleep-wake cycle, synaptic plasticity and memory in adult mammals. Dopaminergic specification in the embryonic ventral midbrain (VM) coincides with increased HA brain levels. To study the effect of HA receptor stimulation on dopamine neuron generation, we administered HA to dopamine progenitors, both in vitro and in vivo. Results Cultured embryonic day 12 (E12) VM neural stem/progenitor cells expressed transcripts for HA receptors H1R, H2R and H3R. Thes...

  6. Integrated optical fiber lattice accumulators

    OpenAIRE

    Atherton, Adam F

    1997-01-01

    Approved for public release; distribution is unlimited. Sigma-delta modulators track a signal by accumulating the error between an input signal and a feedback signal. The accumulated energy is amplitude analyzed by a comparator. The comparator output signal is fed back and subtracted from the input signal. This thesis is primarily concerned with designing accumulators for inclusion in an optical sigma-delta modulator. Fiber lattice structures with optical amplifiers are used to perform the...

  7. Induction of tryptase and histmine release from human colon mast cells by IgE dependent or independent mechanisms

    Institute of Scientific and Technical Information of China (English)

    Shao-Heng He; Hua Xie; Yong-Song He

    2004-01-01

    AIM: To investigate the tryptase and histamine release ability of human colon mast cells upon IgE dependent or independent activation and the potential mechanisms.METHODS: Enzymatically dispersed cells from human colons were challenged with anti-IgE or calcium ionophore A23187, and the cell supernatants after challenge were collected. Both concentration dependent and time course studies with anti-IgE or calcium ionophore A23187 were performed. Tryptase release was determined with a sandwich ELISA procedure and histamine release was measured usina a glass fibre-based fluorometric assay.RESULTS: Both anti-IgE and calcium ionophore were able to induce dose dependent release of histamine from colon mast cells with up to approximately 60% and 25% net histamine release being achieved with 1 μg/mL calcium ionophore and 10 μg/mL anti-IgE, respectively. Dose dependent release of tryptase was also observed with up to approximately 19 ng/mL and 21 ng/mL release of tryptase being achieved with 10 μg/mL anti-IgE and 1 μg/mL calcium ionophore, respectively. Time course study revealed that both tryptase and histamine release from colon mast cells stimulated by anti-IgE initiated within 10 sec and reached their maximum release at 6 min following challenge. Pretreatment of cells with metabolic inhibitors abolished the actions of anti-IgE as well as calcium ionophore. Tryptase and histamine release, particularly that induced by calcium ionophore was inhibited by pretreatment of cells with pertussis toxin.CONCLUSION: Both anti-IgE and calcium ionophore are able to induce significant release of tryptase and histamine from colon mast cells, indicating that this cell type is likely to contribute to the pathogenesis of colitis and other mast cell associated intestinal diseases.

  8. Histamine and histamine-receptor antagonists modify gene expression and biosynthesis of interferon gamma in peripheral human blood mononuclear cells and in CD19-depleted cell subsets

    NARCIS (Netherlands)

    Horváth, B V; Szalai, C; Mándi, Y; László, V; Radvány, Z; Darvas, Z; Falus, A

    1999-01-01

    The effect of histamine and histamine antagonists was examined on gene expression and biosynthesis of bacterial endotoxin (LPS) induced interferon gamma (IFNgamma) both in human peripheral mononuclear cells (PMBC) and in T-cell enriched fractions. We found, that histamine inhibited the LPS induced t

  9. 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 histamine-intol

  10. p Ka calculation of poliprotic acid: histamine

    Science.gov (United States)

    De Abreu, Heitor A.; De Almeida, Wagner B.; Duarte, Hélio A.

    2004-01-01

    Various theoretical studies have been reported addressing the performance of solvation models available to estimate p Ka values. However, no attention has been paid so far to the role played by the electronic, thermal and solvation energy individual contributions to the Gibbs free energy of the deprotonation process. In this work, we decompose the total Gibbs free energy into three distinct terms and then evaluate the dependence of each contribution on the level of theory employed for its determination using different levels of theory. The three possible p Kas of histamine have been estimated and compared with available experimental data. We found that the electronic energy term is sensitive to the level of theory and basis set, and, therefore, could be also a source of error in the theoretical calculation of p Kas.

  11. Pharmacological characterisation of the histamine H3 receptor in the rat hippocampus.

    Science.gov (United States)

    Alves-Rodrigues, A; Timmerman, H; Willems, E; Lemstra, S; Zuiderveld, O P; Leurs, R

    1998-03-30

    The purpose of this report was to pharmacologically characterise the histamine H3 in the rat hippocampus using radioligand binding studies with the H3 receptor antagonist [125I]iodophenpropit and the H3 receptor mediated inhibition of [3H]noradrenaline release. A dissociation constant of 0.33 nM and a maximal number of binding sites of 125 fmol/mg protein were found for [125I]iodophenpropit. Competition studies showed stereoselectivity for the (R) and (S) enantiomers of alpha-methylhistamine and 10 microM of GTPgammaS shifted the curve of (R)-alpha-methylhistamine rightwards. Up to 1 microM, (R)-alpha-methylhistamine displaced only 30% whereas the tested H3-antagonists displaced 50-60% of the total [125I]iodophenpropit bound. This indicates the presence of an additional non-H3 receptor binding site(s) for [125I]iodophenpropit in the rat hippocampus. This secondary site shows low affinity for H3 agonists, but high affinity for the tested H3 antagonists. Electrically evoked [3H]acetylcholine release was shown in slices of rat hippocampus. No H3 receptor modulation of [3H]acetylcholine release from hippocampal slices was detectable. However, H3 receptor activation inhibited 42% of the electrically-evoked [3H]noradrenaline release in rat hippocampal slices. The inhibition of [3H]noradrenaline release was effectively antagonized by the H3 antagonists thioperamide and burimamide. We describe the pharmacological identification of the histamine H3 receptor in the rat hippocampus and its similarities and differences from the cortical H3 receptor. These studies enable us to investigate changes in density and functionality of the hippocampal H3 receptor under (patho)physiological conditions.

  12. 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...... the expression of histamine receptors of the human ES epithelium and sub-epithelial stroma. Following sampling of human endolymphatic sac tissue during translabyrinthine surgery, the expression of histamine receptor genes was determined by cDNA microarray analysis. Results were subsequently verified by immuno......-histochemistry. The combined results of microarrays and immuno-histochemistry showed expression of the histamine receptor HRH1 in the epithelial lining of the ES, whereas HRH3 was expressed exclusively in the sub-epithelial capillary network. Receptors HRH2 and -4 were not expressed. The present data provide the first direct...

  13. Quality assurance of histamine analysis in fresh and canned fish.

    Science.gov (United States)

    Evangelista, Warlley P; Silva, Tarliane M; Guidi, Letícia R; Tette, Patrícia A S; Byrro, Ricardo M D; Santiago-Silva, Paula; Fernandes, Christian; Gloria, Maria Beatriz A

    2016-11-15

    Histamine determination is relevant for fish safety, quality and trade. Recently a study by the European Union (EU) compared the Codex and the EU mandated methods for the analysis of histamine and observed that they underestimated and overestimated the results, respectively. To solve this problem, a simple and efficient procedure for the extraction and quantification of histamine by ion-pair HPLC method with post-column derivatization and fluorimetric detection is proposed. It was optimized and validated for the analysis of histamine in fish. The method attended the performance criteria established by Commission Decision 2002/657/CE. The method was also submitted to proficiency testing; uncertainty was calculated; and the stability of solutions and standards was investigated. There was no matrix effect. The LOD, LOQ, CCα and CCβ were fit for the purpose. The method was successfully used in the analyses of freshwater fish and fresh and canned tuna.

  14. Influencing Factors of Grassland Litter Decomposition and Nutrient Release and Accumulation%草原凋落物的分解及营养元素的释放和累积

    Institute of Scientific and Technical Information of China (English)

    耿元波; 史晶晶

    2012-01-01

    草原凋落物的分解是草原生态系统物质循环的主要环节,其中植物营养元素的释放和累积对退化草场恢复的进程和质量有着重要意义。本文从凋落物自身的性质、外部环境因素(生物及非生物因子)、混合效应等对凋落物分解速率的影响以及凋落物分解时植物营养元素的释放和累积两个方面论述了国内外对草原凋落物的分解及营养元素的生物地球化学行为的研究现状。一般情况下,草原凋落物分解速率与凋落物自身的N、P、K等元素含量正相关,与C/N、C/P、木质素、纤维素等的比值或含量值负相关,而与周围环境中营养元素的组成及含量的关系不大。混合凋落物中不同种类凋落物的N、P含量及物种丰富度影响着非加性效应作用的效果。在凋落物分解过程中,总体趋势表现为分解初级阶段对N的积累,对P和K的释放,而对Na、Ca、Mg等营养元素来说,随物种和根茎叶等部位的不同规律也不一样。凋落物中各元素的含量、凋落物分解阶段、物种类型、非加性效应、土壤环境等都是影响其营养元素释放和累积的因素。据此,本文展望了草原凋落物未来可能的研究方向,指出多因子的交互作用对草原凋落物分解的影响、凋落物混合分解机制探究、某些大量及微量营养元素的释放和累积可能是未来需要研究的重点。%Litter decomposition is a main linkage of material cycle in grassland ecosystem. In the meantime, nutrient elements release and accumulation play an important role in the process of degraded grassland recovery. In this paper, we briefly reviewed the research progress of litter decomposition and the biogeochemical behaviour of nutrient elements in grassland at home and broad from two aspects: the main factors which affect litter decomposition rate, including the properties of litter, external environment (biological and non

  15. Updosing of nonsedating anti-histamines in recalcitrant chronic urticaria

    OpenAIRE

    Kiran Godse; Prachi Bhattar; Sharmila Patil; Nitin Nadkarni; Manjyot Gautam

    2016-01-01

    Chronic urticaria (CU) is a persistent, debiliating condition that causes severe impairment on the quality of life (QoL) of patient by interrupting work productivity. Current guidelines recommend second-generation (nonsedating) anti-histamines for the treatment for all forms of urticaria. In patients who do not respond adequately to conventional doses of anti-histamines, it is recommended to increase the dose to up to four times to obtain control. But there are only few controlled studies tha...

  16. Quantification of Histamine and Carcinine in Drosophila melanogaster Tissues.

    Science.gov (United States)

    Denno, Madelaine E; Privman, Eve; Borman, Ryan P; Wolin, Danielle C; Venton, B Jill

    2016-03-16

    Histamine is a neurotransmitter crucial to the visual processing of Drosophila melanogaster. It is inactivated by metabolism to carcinine, a β-alanyl derivative, and the same enzyme that controls that process also converts dopamine to N-β-alanyl-dopamine. Direct detection of histamine and carcinine has not been reported in single Drosophila brains. Here, we quantify histamine, carcinine, dopamine, and N-β-alanyl-dopamine in Drosophila tissues by capillary electrophoresis coupled to fast-scan cyclic voltammetry (CE-FSCV). Limits of detection were low, 4 ± 1 pg for histamine, 10 ± 4 pg for carcinine, 2.8 ± 0.3 pg for dopamine, and 9 ± 3 pg for N-β-alanyl-dopamine. Tissue content was compared in the brain, eyes, and cuticle from wild-type (Canton S) and mutant (tan(3) and ebony(1)) strains. In tan(3) mutants, the enzyme that produces histamine from carcinine is nonfunctional, whereas in ebony(1) mutants, the enzyme that produces carcinine from histamine is nonfunctional. In all fly strains, the neurotransmitter content was highest in the eyes and there were no strain differences for tissue content in the cuticle. The main finding was that carcinine levels changed significantly in the mutant flies, whereas histamine levels did not. In particular, tan(3) flies had significantly higher carcinine levels in the eyes and brain than Canton S or ebony(1) flies. N-β-Alanyl-dopamine was detected in tan(3) mutants but not in other strains. These results show the utility of CE-FSCV for sensitive detection of histamine and carcinine, which allows a better understanding of their content and metabolism in different types of tissues to be obtained.

  17. [Molecular imaging of histamine receptors in the human brain].

    Science.gov (United States)

    Tashiro, Manabu; Yanai, Kazuhiko

    2007-03-01

    Brain histamine is involved in a wide range of physiological functions such as regulation of sleep-wake cycle, arousal, appetite control, cognition, learning and memory mainly through the 4 receptor subtypes: H1, H2, H3 and H4. Neurons producing histamine, histaminergic neurons, are exclusively located in the tuberomammillary nucleus of the posterior hypothalamus and are transmitting histamine to almost all regions of the brain. Roles of brain histamine have been studied using animals including knock-out mice and human subjects. For clinical studies, molecular imaging technique such as positron emission tomography (PET), with ligands such as [11C]doxepin and [11C]pyrilamine, has been a useful tool. A series of clinical studies on histamine H1 antagonists, or antihistamines, have demonstrated that antihistamines can be classified into sedative, mildly-sedative and non-sedative drugs according to their blood-brain barrier (BBB) permeability, showing apparent clinical usefulness regarding QOL, work efficiency and traffic safety of allergic patients. PET has also been used for elucidation of aging effects and pathophysiological roles of histaminergic nervous system in various neuropsychiatric disorders such as Alzheimer's disease, schizophrenia and depression, where H1 receptor binding potentials were lower than age-matched healthy controls. It has been also demonstrated that brain histamine functions as an endogenous anti-epileptic. In addition, H3 receptors are located in the presynaptic sites of not only histaminergic nerves but also in other nervous systems such as serotonergic, cholinergic and dopaminergic systems, and to be regulating secretion of various neurotransmitters. Nowadays, H3 receptors have been thought to be a new target of drug treatment of various neuropsychiatric disorders. There are still many research topics to be investigated regarding molecular imaging of histamine and histamine receptors. The authors hope that this line of research contributes

  18. Multiple Targeting Approaches on Histamine H3 Receptor Antagonists

    OpenAIRE

    Mohammad eKhanfar; Anna eAffini; Kiril eLutsenko; Katarina eNikolic; Stefania eButini; Holger eStark

    2016-01-01

    With the very recent market approval of pitolisant (Wakix®), the interest in clinical applications of novel multifunctional histamine H3 receptor antagonists has clearly increased. Since histamine H3 receptor antagonists in clinical development have been tested for a variety of different indications, the combination of pharmacological properties in one molecule for improved pharmacological effects and reduced unwanted side-effects is rationally based on the increasing knowledge on the complex...

  19. The role of histamine in the cardiovascular system.

    Science.gov (United States)

    Cabanié, M; Godfraind, T

    1988-01-01

    This article reviews briefly the role of histamine through its H1 and H2 receptors on the cardiovascular system and its action on calcium and catecholamines. The analogy between the adrenergic and the histaminergic systems is well demonstrated and there is evidence that histamine participates in myocardial damage and arrythmias, but the question of its exact role in the early stages of cardiovascular diseases, such as myocardial ischaemia and atherosclerosis, requires further study.

  20. Histamine inhibits differentiation of skin fibroblasts into myofibroblasts.

    Science.gov (United States)

    Lin, Lin; Yamagata, Kaoru; Nakayamada, Shingo; Sawamukai, Norifumi; Yamaoka, Kunihiro; Sakata, Kei; Nakano, Kazuhisa; Tanaka, Yoshiya

    2015-07-31

    Histamine and TGF-β, major mediators secreted by mast cells, are involved in skin inflammation and play critical roles in the pathogenesis of systemic sclerosis. However, the roles of signaling mechanisms in the development of skin fibrosis remain largely unclear. Here we show that histamine suppressed the expression of α smooth muscle actin (αSMA), a marker of myofibroblasts, induced by TGF-β1 in skin fibroblasts. Histamine H1-receptor (H1R), but not H2-receptor (H2R) or H4-receptor (H4R), was expressed on skin fibroblasts at both mRNA and protein levels. Interestingly, an H1R antagonist, but not H2R or H4R antagonists, antagonized the histamine-mediated suppression of αSMA expression by TGF-β1. Correspondingly, phosphorylated Smad2 was detected after treatment with TGF-β1, whereas the addition of histamine inhibited this phosphorylation. Taken together, histamine-H1R decreased TGF-β1-mediated Smad2 phosphorylation and inhibited differentiation of skin fibroblasts into myofibroblasts.

  1. 控释碘肥对生菜富碘及若干生理特性的影响%Effects of controlled-release iodine fertilizers on iodine accumulation and some physiological characteristics of lettuce

    Institute of Scientific and Technical Information of China (English)

    陈海宁; 张民; 孙瑶

    2012-01-01

    A greenhouse pot experiment was conducted to assess the effects of controlledrelease iodine fertilizers on the iodine accumulation and physiological response of lettuce in comparison with traditional iodine fertilizers. The plants were subjected to different iodine fertilizers containing two levels of iodine as iodate or iodide, 10 and 20 mg/kg soil. The results show that all the treatments with iodine applied significantly increase the iodine contents in leaves of lettuce. The leaf iodine contents developed from the controlledrelease potassium iodate and the controlledrelease potassium iodide are significantly enhanced by 46.60%-61.16% and 46.59%-58.53% in comparison with the corresponding traditional iodine fertilizers, respectively. The biomass amounts (fresh mass and dry mass of shoot and root) and leaf chlorophyll contents of lettuce grown with the controlledrelease iodine fertilizers are higher than those of the traditional iodine fertilizers. The growthpromoting function is also associated with the increases of vitamin C and activities of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) in lettuce leaves. Application of the controlledrelease iodine fertilizers results in the reduced NO-3-N content and diminished lipid peroxidation (MDA) content of lettuce leaves. Amount of iodine in leachate peaked with controlledrelease iodine fertilizers are higher than those of the traditional iodine fertilizers. The controlledrelease potassium iodate and the controlledrelease potassium iodide also significantly reduce the iodine leached rates by 45.99%-50.97% and 39.18%-46.29% compared to the traditional fertilizers, respectively. When iodine applied rate is 20 mg/kg soil, the leaf iodine content is significantly higher than that of the 10 mg/kg soil, while no significant differences are found in other indexes. Overall, the controlledrelease iodine fertilizers increase iodine accumulation in lettuce leaves

  2. Genetic Variation in the Histamine Production, Response, and Degradation Pathway Is Associated with Histamine Pharmacodynamic Response in Children with Asthma

    Science.gov (United States)

    Jones, Bridgette L.; Sherwin, Catherine M. T.; Liu, Xiaoxi; Dai, Hongying; Vyhlidal, Carrie A.

    2017-01-01

    Introduction: There is growing knowledge of the wide ranging effects of histamine throughout the body therefore it is important to better understand the effects of this amine in patients with asthma. We aimed to explore the association between histamine pharmacodynamic (PD) response and genetic variation in the histamine pathway in children with asthma. Methods: Histamine Iontophoresis with Laser Doppler Monitoring (HILD) was performed in children with asthma and estimates for area under the effect curve (AUEC), maximal response over baseline (Emax), and time of Emax (Tmax) were calculated using non-compartmental analysis and non-linear mixed-effects model with a linked effect PK/PD model. DNA isolation and genotyping were performed among participants to detect known single nucleotide polymorphisms (SNPs) (n = 10) among genes (HDC, HNMT, ABP1, HRH1, HRH4) within the histamine pathway. General linear model was used to identify associations between histamine related genetic variants and measured histamine PD response parameters. Results: Genotyping and HILD response profiles were completed for 163 children. ABP1 47 C/T, ABP1 4107, and HNMT-1639 C/Twere associated with Emax (ABP1 47 CC genotype mean Emax 167.21 vs. CT/TT genotype mean Emax 139.20, p = 0.04; ABP1 4107 CC genotype mean Emax 141.72 vs. CG/GG genotype mean Emax 156.09, p = 0.005; HNMT-1639 CC genotype mean Emax 132.62 vs. CT/TT genotype mean Emax 155.3, p = 0.02). In a stratified analysis among African American children only, ABP1 and HNMT SNPs were also associated with PD response; HRH4 413 CC genotype was associated with lower Emax, p = 0.009. Conclusions: We show for the first time that histamine pathway genetic variation is associated with measureable changes in histamine response in children with asthma. The variability in histamine response and impact of histamine pathway genotype is important to further explore in patients with asthma so as to improve disease phenotyping leading to more

  3. Histamine H3 receptors aggravate cerebral ischaemic injury by histamine-independent mechanisms

    OpenAIRE

    Yan, Haijing; Zhang, Xiangnan; Hu, Weiwei; Ma, Jing; Hou, Weiwei; Zhang, Xingzhou; Wang, Xiaofen; Gao, Jieqiong; Yao SHEN; Lv, Jianxin; Ohtsu, Hiroshi; Han, Feng; Wang, Guanghui; Chen, Zhong

    2014-01-01

    The role of the histamine H3 receptor (H3R) in cerebral ischaemia/reperfusion (I/R) injury remains unknown. Here we show that H3R expression is upregulated after I/R in two mouse models. H3R antagonists and H3R knockout attenuate I/R injury, which is reversed by an H3R-selective agonist. Interestingly, H1R and H2R antagonists, a histidine decarboxylase (HDC) inhibitor and HDC knockout all fail to compromise the protection by H3R blockade. H3R blockade inhibits mTOR phosphorylation and reinfor...

  4. 2-Thiazolylethylamine, a selective histamine H1 agonist, decreases seizure susceptibility in mice.

    Science.gov (United States)

    Yokoyama, H; Onodera, K; Iinuma, K; Watanabe, T

    1994-03-01

    The effects of intracerebroventricular (ICV) administration of histamine and its selective agonists on electrically and pentylenetetrazole-induced convulsions in mice were studied. The ICV administration of histamine decreased seizure susceptibility on electrically and pentylenetetrazole-induced convulsions significantly and dose-dependently. The inhibitory effects of histamine were well antagonized by centrally acting histamine H1 antagonists such as pyrilamine (or mepyramine) and ketotifen, but not by a peripherally acting histamine H1 antagonist, astemizole, or a centrally acting H2 antagonist, zolantidine. The ICV administration of 2-thiazolylethylamine, a selective histamine H1 agonist, also decreased seizure susceptibility, which could be antagonized by centrally acting histamine H1 antagonists, whereas dimaprit, a selective histamine H2 agonist, did not affect seizure susceptibility. These findings strengthened the idea that the central histaminergic neuron system plays an inhibitory role in convulsions.

  5. The therapeutic potential of histamine receptor ligands in inflammatory bowel disease.

    Science.gov (United States)

    Neumann, Detlef; Seifert, Roland

    2014-09-01

    In the intestine of patients suffering from inflammatory bowel disease concentrations of histamine are increased compared to healthy controls. Genetic ablation of histamine production in mice ameliorates the course of experimentally induced colitis. These observations and first pharmacological studies indicate a function of histamine in the pathogenesis of inflammatory bowel disease. However, a closer examination reveals that available data are highly heterogeneous, limiting the rational design of strategies addressing specific histamine receptor subtypes as possible target for pharmacological interaction. However, very recently first clinical data indicate that antagonism at the histamine receptor subtype H4 provides a beneficial effect in at least the skin. Here, we discuss the available data on histamine effects and histamine receptor subtype functions in inflammatory bowel disease with a special emphasis on the histamine H4-receptor.

  6. Detection of Histamine in Fish and Fishery Products in Osaka Prefecture (Fiscal 2015 Report).

    Science.gov (United States)

    Awazu, Kaoru; Takatori, Satoshi; Kakimoto, Sachiko; Nomura, Chie; Masayama, Atsushi; Yamaguchi, Mizuka; Kakimoto, You; Kajimura, Keiji

    2017-01-01

    Histamine food poisoning is caused by ingestion of spoiled fish containing high levels of histamine. This paper reports cases in which histamine was detected in Osaka prefecture in fiscal year 2015 in a survey of fish and fishery products on the market and the food poisoning. A suspected case of histamine food poisoning was also evaluated to investigate the cause and minimize further problems. Histamine in food was separated on SPE cartridge columns, and analyzed after derivatization with fluorescamine by means of HPLC-FL. Histamine was detected in some fishery products on the market and in food that had caused poisoning. The samples in which histamine was detected were semi-dried whole round herring (Urumeiwashi-maruboshi), mackerel (Saba) and sardine dumpling (Iwashi-tsumire). These foods were the main causes of histamine food poisoning according to the report of the Ministry of Health, Labour and Welfare, Government of Japan.

  7. The Histamine H4 Receptor: From Orphan to the Clinic

    Directory of Open Access Journals (Sweden)

    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

  8. Evidence that histamine is the inhibitory transmitter of the auditory interneuron ON1 of crickets.

    Science.gov (United States)

    Skiebe, P; Corrette, B J; Wiese, K

    1990-08-24

    The omega neurons of crickets are connected with each other by reciprocal inhibition. This inhibition could be mimicked by bath-applied histamine and blocked by histamine H1-antagonists. Histamine, like ON1, also influenced the ascending interneuron AN2, so that its response pattern more closely reflected the temporal structure of the calling song. This evidence strongly suggests that histamine is the inhibitory transmitter of the ON1s.

  9. Neuronal histamine and cognitive symptoms in Alzheimer's disease.

    Science.gov (United States)

    Zlomuzica, Armin; Dere, Dorothea; Binder, Sonja; De Souza Silva, Maria Angelica; Huston, Joseph P; Dere, Ekrem

    2016-07-01

    Alzheimer's disease is a neurodegenerative disorder characterized by extracellular amyloid plaque deposits, mainly composed of amyloid-beta peptide and intracellular neurofibrillary tangles consisting of aggregated hyperphosphorylated tau protein. Amyloid-beta represents a neurotoxic proteolytic cleavage product of amyloid precursor protein. The progressive cognitive decline that is associated with Alzheimer's disease has been mainly attributed to a deficit in cholinergic neurotransmission due to the continuous degeneration of cholinergic neurons e.g. in the basal forebrain. There is evidence suggesting that other neurotransmitter systems including neuronal histamine also contribute to the development and maintenance of Alzheimer's disease-related cognitive deficits. Pathological changes in the neuronal histaminergic system of such patients are highly predictive of ensuing cognitive deficits. Furthermore, histamine-related drugs, including histamine 3 receptor antagonists, have been demonstrated to alleviate cognitive symptoms in Alzheimer's disease. This review summarizes findings from animal and clinical research on the relationship between the neuronal histaminergic system and cognitive deterioration in Alzheimer's disease. The significance of the neuronal histaminergic system as a promising target for the development of more effective drugs for the treatment of cognitive symptoms is discussed. Furthermore, the option to use histamine-related agents as neurogenesis-stimulating therapy that counteracts progressive brain atrophy in Alzheimer's disease is considered. This article is part of a Special Issue entitled 'Histamine Receptors'.

  10. [Isoforms of the human histamine H3 receptor: Generation, expression in the central nervous system and functional implications].

    Science.gov (United States)

    García-Gálvez, Ana Maricela; Arias-Montaño, José Antonio

    2016-01-01

    Histamine plays a significant role as a neuromodulator in the human central nervous system. Histamine-releasing neurons are exclusively located in the tuberomammillary nucleus of the hypothalamus, project to all major areas of the brain, and participate in functions such as the regulation of sleep/wakefulness, locomotor activity, feeding and drinking, analgesia, learning, and memory. The functional effects of histamine are exerted through the activation of four G protein-coupled receptors (H1, H2, H3 and H4), and in the central nervous system the first three receptors are widely expressed. The H3 receptor (H3R) is found exclusively in neuronal cells, where it functions as auto- and hetero-receptor. One remarkable characteristic of the H3R is the existence of isoforms, generated by alternative splicing of the messenger RNA. For the human H3R, 20 isoforms have been reported; although a significant number lack those regions required for agonist binding or receptor signaling, at least five isoforms appear functional upon heterologous expression. In this work we review the evidence for the generation of human H3R isoforms, their expression, and the available information regarding the functionality of such receptors.

  11. 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...... with or without histamine dihydrochloride (HDC) in patients with metastatic renal cell carcinoma (mRCC) were run in parallel. A total of 41 patients were included in Manchester, UK and 63 in Aarhus, Denmark. The self-administered, outpatient regimen included IL-2 as a fixed dose, 18 MIU s.c. once daily, 5 days...... median survival (18.3 vs 11.4 months, P = 0.07), time to PD (4.5 vs 2.2 months, P = 0.13) and clinical benefit (CR + PR + SD) (58 vs 37%, P = 0.10) in favour of IL-2/HDC, whereas the UK study was negative for all end points. Only three patients had grade 4 toxicity; however, two were fatal. A randomised...

  12. Involvement of Histamine and RhoA/ROCK in Penicillin Immediate Hypersensitivity Reactions.

    Science.gov (United States)

    Han, Jiayin; Yi, Yan; Li, Chunying; Zhang, Yushi; Wang, Lianmei; Zhao, Yong; Pan, Chen; Liang, Aihua

    2016-09-13

    The mechanism of penicillin immediate hypersensitivity reactions has not been completely elucidated. These reactions are generally considered to be mediated by IgE, but penicillin-specific IgE could not be detected in most cases. This study demonstrated that penicillin was able to cause vascular hyperpermeability in a mouse model mimicking clinical symptoms of penicillin immediate hypersensitivity reactions. The first exposure to penicillin also induced immediate edema and exudative reactions in ears and lungs of mice in a dose-dependent manner. Vasodilation was noted in microvessels in ears. These reactions were unlikely to be immune-mediated reactions, because no penicillin-specific IgE was produced. Furthermore, penicillin treatment directly elicited rapid histamine release. Penicillin also led to F-actin reorganization in human umbilical vein endothelial cells and increased the permeability of the endothelial monolayer. Activation of the RhoA/ROCK signaling pathway was observed in ears and lungs of mice and in endothelial cells after treatment with penicillin. Both an anti-histamine agent and a ROCK inhibitor attenuated penicillin immediate hypersensitivity reactions in mice. This study presents a novel mechanism of penicillin immediate hypersensitivity reactions and suggests a potential preventive approach against these reactions.

  13. The magnificent two: histamine and the H3 receptor as key modulators of striatal circuitry.

    Science.gov (United States)

    Rapanelli, Maximiliano

    2017-02-06

    Histaminergic dysfunction has been recently linked to tic disorders and to aberrant striatal function. There is a particular interest in the histamine 3 receptor (H3R) due to its clinical implications for treating multiple disorders and its high expression in the brain. Striatal histamine (HA) modulates through the H3R in complex ways the release of striatal neurotransmitters into this brain region. The H3R has been classically described to be coupled to Gi, although there is evidence that revealed that striatal H3R forms heteromers with the dopamine receptors 1 and 2 in the medium spiny neurons (MSNs) than changes this signaling. Moreover, new data described for the first time a complete, segregated and time dependent signaling after H3R activation in the two types of MSNs (D1R-MSNs and D2R-MSNs). The aim of this review is to update the role of HA and H3R in striatal function at a molecular and signaling levels.

  14. Changes in ocular mast cell numbers and histamine distribution during experimental autoimmune uveitis.

    Science.gov (United States)

    Lee, C H; Lang, L S; Orr, E L

    1993-01-01

    Choroidal mast cells have been implicated in experimental autoimmune uveitis (EAU), an ocular inflammatory disease induced by S-antigen. Our data confirm that choroidal mast cell numbers decrease with clinical onset of S-antigen-induced EAU in Lewis rats, and establish that the decrease is statistically significant. In addition, we find that the numbers of limbal mast cells also decrease during S-antigen-induced EAU, and that this decrease occurs earlier in the course of the disease than that observed for choroidal mast cells. Activation and degranulation of mast cells, as evidenced by decreases in mast cell number, result in the synthesis and/or release of large quantities of mast cell mediators, such as histamine. Histamine levels in EAU were found to change significantly, decreasing in the anterior portion of the eye and increasing in the choroid and retina, in concert with changes in mast cell number over the course of EAU. Mast cell mediators may actively contribute to the pathogenesis of EAU through direct enhancement of the inflammation, by stimulation of other elements of the immune system, and/or through facilitation of the blood-retinal barrier breakdown that occurs in EAU. Overall, these results add to the evidence for a mast cell role in EAU, and, in addition, show that the mast cell involvement in EAU includes the mast cells of the limbus.

  15. Histamine H3 receptor agonists decrease hypothalamic histamine levels and increase stereotypical biting in mice challenged with methamphetamine.

    Science.gov (United States)

    Kitanaka, Junichi; Kitanaka, Nobue; Hall, F Scott; Uhl, George R; Tatsuta, Tomohiro; Morita, Yoshio; Tanaka, Koh-ichi; Nishiyama, Nobuyoshi; Takemura, Motohiko

    2011-10-01

    The effects of the histamine H(3) receptor agonists (R)-α-methylhistamine, imetit and immepip on methamphetamine (METH)-induced stereotypical behavior were examined in mice. The administration of METH (10 mg/kg, i.p.) to male ddY mice induced behaviors including persistent locomotion and stereotypical behaviors, which were classified into four categories: stereotypical head-bobbing (1.9%), circling (1.7%), sniffing (14.3%), and biting (82.1%). Pretreatment with (R)-α-methylhistamine (3 and 10 mg/kg, i.p.) significantly decreased stereotypical sniffing, but increased stereotypical biting induced by METH, in a dose-dependent manner. This effect of (R)-α-methylhistamine on behavior was mimicked by imetit or immepip (brain-penetrating selective histamine H(3) receptor agonists; 10 mg/kg, i.p. for each drug). Hypothalamic histamine levels 1 h after METH challenge were significantly increased in mice pretreated with saline. These increases in histamine levels were significantly decreased by pretreatment with histamine H(3) receptor agonists, effects which would appear to underlie the shift from METH-induced stereotypical sniffing to biting.

  16. 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.

  17. The role of histamine in the cardiovascular effects of atracurium.

    Science.gov (United States)

    Adt, M; Baumert, J H; Reimann, H J

    1992-02-01

    We have investigated the effect of a bolus injection of atracurium 0.6 mg kg-1 on the cardiovascular system in 16 patients undergoing aortocoronary bypass surgery. H1- and H2-receptor antagonists were administered to eight patients before the neuromuscular blocker. A standard anaesthetic was used comprising fentanyl, flunitrazepam, etomidate and enflurane. After administration of atracurium, haemodynamic changes and plasma histamine concentrations were measured at frequent intervals. In the first group, who received only atracurium, a brief but marked decrease in SVR and MAP occurred, accompanied by an increase in Cl, together with a marked increase in plasma concentration of histamine. In the second group, who received H1- and H2-receptor block, there was no decrease in MAP and only a small increase in plasma histamine concentration. However, there were significant changes in SVR and Cl similar to those in atracurium group.

  18. Histamine and H3 receptor in alcohol-related behaviors.

    Science.gov (United States)

    Panula, Pertti; Nuutinen, Saara

    2011-01-01

    Data from rat models for alcohol preference and histidine decarboxylase knockout (HDC KO) mice suggest that brain histamine regulates alcohol-related behaviors. Histamine levels are higher in alcohol-preferring than in alcohol-nonpreferring rat brains, and expression of histamine H(3) receptor (H(3)R) is different in key areas for addictive behavior. H(3)R inverse agonists decrease alcohol responding in one alcohol-preferring rat line. Conditioned place preference induced by alcohol is stronger in HDC KO mice than in control mice. The HDC KO mice display a weaker stimulatory response to acute alcohol than the wild-type (WT) mice. In male inbred C57BL/6 mice the H(3)R antagonist ciproxifan inhibits ethanol-evoked stimulation of locomotor activity. Ciproxifan also potentiates the ethanol reward, but does not alone result in the development of place preference. At least in one rat model developed to study alcohol sensitivity high histamine levels are characteristic of the alcohol-insensitive rat line, and lowering brain histamine with a HDC inhibitor increases alcohol sensitivity in the tilting plane test. However, the motor skills of HDC KO mice do not seem to differ from those of the WT mice. Current evidence suggests that the histaminergic system is involved in the regulation of place preference behavior triggered by alcohol, possibly through an interaction with the mesolimbic dopamine system. Histamine may also interact with dopamine in the regulation of the cortico-striato-pallido-thalamo-cortical motor pathway and cerebellar mechanisms, which may be important in different motor behaviors beyond alcohol-induced motor disturbances. H(3)R ligands may have significant effects on alcohol addiction.

  19. Dose-dependent effect of histamine on antibody generationin vivo

    Institute of Scientific and Technical Information of China (English)

    Tripathi T; Shahid M; Khan HM; Khan RA; Siddiqui MU

    2010-01-01

    Objective:To delineate immunomodulatory role of histamine on antibody generation profile in rabbit in the present dose-dependent histamine study.Methods: The cohort comprised of three groups (III, IV and V), containing six rabbits each, and received subcutaneous histamine 50 μg/kgíbis in die (b.i.d.), 100 μg/kg í b.i.d. and 200 μg/kgíb.i.d., respectively for 10 days (starting from the 1st day). They were subsequently immunized on the 3rd day with intravenous injection of sheep blood cell (SRBC) (1í109 cells/mL). Group II (positive control) (n=6) received vehicle (sterile distilled water) and immunized at day 3 similarly while group I (negative control) (n=6) remained non-immunized and received only vehicle. All experimentations were performed in triplicate. Blood samples were collected on pre-immunization (pre-I) (day 0), as well as on days 7-, 14-, 21-, 28- and 58- post-immunization (post-I). Immunological parameters [total immunoglobulins (Igs), IgM and IgG] were analyzed by enzyme linked immunosorbent assay (ELISA) technique.Results: Histamine could influence a detectable antibody response to SRBC as early as day 7-post-I, which lasted until day 58- post-I. The results were found statistically significant (P< 0.05).Conclusions: Our results provide evidence that histamine has a short-term effect on antibody generation (until its presence in the body), and the antibody generation titerin vivowere affected by the concentration of histamine.

  20. Substance P is involved in the effect of histamine H3 receptor agonist, Sch 50971 on nasal allergic symptoms in mice.

    Science.gov (United States)

    Yokota, Emiko; Kuyama, Shoji; Ogawa, Masami; Kamei, Chiaki

    2008-08-01

    The aim of this study was to clarify the mechanisms of the inhibitory effect of a histamine H3 receptor agonist, Sch 50971, on nasal signs in an allergic rhinitis model in mice. The severity of allergic rhinitis was assessed by determining the extent of two markers of allergic symptoms (sneezing and nasal rubbing). The topical application of a histamine H3 receptor antagonist, clobenpropit, into the nasal cavities resulted in a dose-dependent increase in sneezing and nasal rubbing, and both Sch 50971 and a tachykinin NK1 receptor antagonist, L-733,060, inhibited these reactions in non-sensitized mice. Sch 50971 caused no inhibition of histamine- and substance P-induced nasal symptoms; however, the reactions induced by capsaicin were significantly decreased by Sch 50971 in non-sensitized mice. Sch 50971 and cetirizine inhibited antigen-induced sneezing and nasal rubbing in sensitized mice. On the other hand, cetirizine inhibited nasal symptoms induced by antigen in capsaicin-pretreated mice, whereas no effect was observed in Sch 50971. From these results, we concluded that Sch 50971 blocked nasal symptoms by the inhibition of substance P release via histamine H3 receptors located on peri]pheral sensory nerve endings.

  1. Computational Evaluation of 2-Phenyl-4H-chromen-4-one Analogues as Antihistamines: Potential Histamine N-Methyltransferase (HMT Inhibitors

    Directory of Open Access Journals (Sweden)

    Shikha S. Dave

    2009-01-01

    Full Text Available Abnormal release of histamine, which is present in relatively high concentration in the lungs, causes serious allergic vasoconstriction and anaphylactic manifestation in human beings. In mammals, a major pathway of histamine metabolism in the lungs is mediated by histamine N-methyl transferase (HMT and diamine oxidase. The need to design a strategy of mechanistic computational evaluation of protein-ligand affinity i.e. HMT- 2-phenyl-4H-chromen-4-ones, protein complex binding energy has been established. A library of synthesized 2-phenyl-4H-chromen-4-ones was docked into the active site cavity of target protein, HMT (Pdb: 2aot. The high-resolution crystal structure of HMT complex with the competitive inhibitor N [2 (benzhydryloxyethyl] N N-Dimethylamine (Diphenhydramine revealed a protein with a highly confined binding region that could be targeted in the design of specific anti-histamines. The validation of docking programme by Potential Mean Force was compared with binding energy results of known ligands in the active sites of HMT, diphenhydramine / benadryl, promethazine, cyproheptadine, trimeton / avil etc. All the synthesized chromone derivatives showed comparable negative binding energies pointing towards the fact that these molecules could be potent antihistamines.

  2. Mast cells and histamine play an important role in edema and leukocyte recruitment induced by Potamotrygon motoro stingray venom in mice.

    Science.gov (United States)

    Kimura, Louise F; Prezotto-Neto, José Pedro; Távora, Bianca C L F; Faquim-Mauro, Eliana L; Pereira, Nicole A; Antoniazzi, Marta M; Jared, Simone G S; Teixeira, Catarina F P; Santoro, Marcelo L; Barbaro, Katia C

    2015-09-01

    This work aimed to investigate mechanisms underlying the inflammatory response caused by Potamotrygon motoro stingray venom (PmV) in mouse paws. Pre-treatment of animals with a mast cell degranulation inhibitor (cromolyn) diminished edema (62% of inhibition) and leukocyte influx into the site of PmV injection. Promethazine (histamine type 1 receptor antagonist) or thioperamide (histamine type 3 and 4 receptor antagonist) also decreased edema (up to 30%) and leukocyte numbers, mainly neutrophils (40-50 %). Cimetidine (histamine type 2 receptor antagonist) had no effect on PmV-induced inflammation. In the RBL-2H3 lineage of mast cells, PmV caused proper cell activation, in a dose-dependent manner, with release of PGD2 and PGE2. In addition, the role of COXs products on PmV inflammatory response was evaluated. Indomethacin (COX-1/COX-2 inhibitor) or etoricoxib (COX-2 inhibitor) partially diminished edema (around 20%) in PmV-injected mice. Indomethacin, but not etoricoxib, modulated neutrophil influx into the site of venom injection. In conclusion, mast cell degranulation and histamine, besides COXs products, play an important role in PmV-induced reaction. Since PmV mechanism of action remains unknown, hindering accurate treatment, clinical studies can be performed to validate the prescription of antihistaminic drugs, besides NSAIDs, to patients injured by freshwater stingrays.

  3. Histamine H2 receptor - Involvement in gastric ulceration

    Science.gov (United States)

    Brown, P. A.; Vernikos-Danellis, J.; Brown, T. H.

    1976-01-01

    The involvement of the H1 and H2 receptors for histamine in the pathogenesis of gastric ulcers was investigated in rats. Metiamide, an H2 receptor antagonist, reliably reduced ulceration produced by stress alone or by a combination of stress and aspirin. In contrast, pyrilamine, which blocks only the H1 receptor, was without effect under these same conditions. The results support the hypothesis that histamine mediates both stress and stress plus aspirin induced ulceration by a mechanism involving the H2 receptor.

  4. Histamine and the antiallergic antihistamines: a history of their discoveries.

    Science.gov (United States)

    Emanuel, M B

    1999-07-01

    The paper provides a historical overview of the discovery of both histamine and the H1 antihistamines. The context of these discoveries is provided in relation to the development of medicinal chemistry during the 19th century. Background is provided on the history of discovery of mechanisms of anaphylaxis and allergy and the immunology of hypersensitivity at the end of the 19th and early 20th century. The discovery of histamine and the antihistamines is then discussed in relation to the development of pharmacological receptor theory culminating in the discovery of the first antihistamines in the 1930s and their widespread clinical introduction in the 1940s.

  5. [Determination of histamine content in canned fish products determined by the colorimetry method of Hardy and Smith].

    Science.gov (United States)

    Windyga, B; Grochowska, A; Sciezyńska, H; Górecka, K; Fonberg-Broczek, M

    1992-01-01

    The content of histamine in 79 samples of imported canned fish products (sardines, mackerel) was determined. Histamine was assayed by colorimetric method of Hardy and Smith. In 18% of tested products (sardines) levels of histamine were exceeded 20 mg/100 of product. Usefulness of this method in routine quantitative determination of histamine content in canned fish products was documented.

  6. Influence of dietary low histamine diets in the development of chemical kindling induced by pentylenetetrazole in Sprague Dawley rats

    Institute of Scientific and Technical Information of China (English)

    JinChun-lei; ZhangLi-san; XuLi-sa; YanaiKazuhiko; ChenZhong

    2004-01-01

    A role for dietary low histamine diets (LH) on the seizure development of pentylenetetrazole (PTZ)-induced kindling and excitatory behavior was examined in rats. The chemical kindling started after 14 days of dietary treatment with LH( containing 0.145mol/g of histamine) . As compared with the basal histamine diets (BH, containing 7.28 mol/g of histamine)

  7. Formation of histamine and biogenic amines in cold-smoked tuna: An investigation of psychrotolerant bacteria from samples implicated in cases of histamine fish poisoning

    DEFF Research Database (Denmark)

    Emborg, Jette; Dalgaard, Paw

    2006-01-01

    Two outbreaks and a single case of histamine fish poisoning associated with cold-smoked tuna (CST) were reported in Denmark during 2004. The bacteria most likely responsible for histamine formation in CST implicated in histamine fish poisoning was identified for the first time in this study....... Product characteristics and profiles of biogenic amines in the implicated products were also recorded. In the single poisoning case, psychrotolerant Morganella morganii -like bacteria most likely was responsible for the histamine production in CST with 2.2% ñ 0.6% NaCl in the water phase (WPS......). In outbreak 1, Photobacterium phosphoreum most likely formed the histamine in CST with 1.3% ñ 0.1% WPS. In outbreak 2, which involved 10 persons, the bacteria responsible for histamine formation could not be determined. The measured concentrations of WPS were very low compared with those of randomly collected...

  8. Slope of the dose-response curve: usefulness in assessing bronchial responses to inhaled histamine.

    OpenAIRE

    Cockcroft, D. W.; Berscheid, B A

    1983-01-01

    The value of determining the slope of the histamine dose-response curve, in addition to the histamine provocation concentration producing a 20% reduction in FEV1 (PC20-FEV1), was assessed by analysis of histamine dose-response curves in 40 patients selected as having a wide range of increased non-specific bronchial responsiveness to inhaled histamine. The histamine dose-response curves were found to be fit the linear curve (dose v response, mean r2 = 0.97) better than the logarithmic curve (l...

  9. Structure-activity relationship of polyphenols on inhibition of chemical mediator release from rat peritoneal exudate cells.

    Science.gov (United States)

    Yamada, K; Shoji, K; Mori, M; Ueyama, T; Matsuo, N; Oka, S; Nishiyama, K; Sugano, M

    1999-03-01

    The effect of phenolic compounds in foodstuffs on histamine and leukotriene B4 (LTB4) release from rat peritoneal exudate cells and their antioxidative activity were examined to assess their antiallergenic activities. Among them, triphenols such as pyrogallol and gallic acid inhibited histamine release from the cells, but diphenols did not. On the other hand, o- and p-diphenols such as catechol and hydroquinone with strong antioxidative activity inhibited LTB4 release as strongly as pyrogallol, but an m-derivative resorcinol with weak antioxidative activity did not. Though carboxylated compounds and their noncarboxylated counterparts were antioxidative, the former exerted a much weaker inhibitory effect on the LTB4 release than the latter. In flavonols, only myricetin with a triphenolic B ring strongly inhibited histamine release, but all flavonols strongly suppressed LTB4 release irrespective of the number of OH groups in the B ring. Among flavonoids with an o-diphenolic B ring, flavonol and flavone with a C4-carbonyl group strongly inhibited LTB4 release, whereas the activity of anthocyan without C4-carbonyl was much weaker than the above compounds. These results suggest that triphenolic structure is essential for the inhibition of histamine release. On the other hand, antioxidative activity and membrane permeability of phenolic compounds seemed to be essential for the inhibition of LTB4 release. In addition, the C4-carbonyl group seemed to be important for strongly inhibiting LTB4 release.

  10. Effect of histamine on regional cerebral blood flow of the parietal lobe in rats.

    Science.gov (United States)

    Yang, Peng-Bo; Chen, Xin-Lin; Zhao, Jian-Jun; Zhang, Jian-Shui; Zhang, Jun-Feng; Tian, Yu-Mei; Liu, Yong

    2010-09-01

    Histamine is a powerful modulator that regulates blood vessels and blood flow. The effect of histamine on the extracortical vessels has been well described, while much less is known about the effect of histamine on intracortical vessels. In this study, we investigated the effect of histamine on regional cerebral blood flow in rat parietal lobe with laser Doppler flowmetry. The pharmacological characteristics of distinct ways (intracerebroventricular injection, intraperitoneal injection, and cranial window infusion) in applying histamine to the brain were also obtained and compared. Histamine applied in three ways all produced a decrease of rCBF in parietal lobe in a concentration-dependent manner. Cranial window infusion was the most effective way and intraperitoneal injection of L-histidine was the most ineffective, although it is a simple and applied way. To determine which type of receptor takes part in the vessel contraction induced by histamine, H1 receptor antagonist, diphenhydramine, and H2 receptor antagonist, cimetidine, were applied, respectively, before histamine administration. When the injection of cimetidine was conducted in advance, histamine still resulted in a decrease of infusion amount; while the injection of diphenhydramine was conducted in advance, the infusion of blood amount wasn't changed. These findings indicated that histamine could result in a reduction of rCBF in the rat parietal lobe and this effect of histamine may attribute partly to its combination with H1 receptor.

  11. A Surface Plasmon Resonance Histamine Sensor Based on an Electropolymerized Molecularly Imprinted Polymer (E-MIP

    Directory of Open Access Journals (Sweden)

    Hubilla Frances Adeline D.

    2017-01-01

    Full Text Available In this paper, histamine sensing by surface plasmon resonance (SPR spectroscopy using an electropolymerized molecularly imprinted polymer (E-MIP of functionalized polyterthiophene and histamine is reported. The MIP histamine sensor showed good linear relationship (R2 = 0.995 between the SPR angle shift and the logarithm of histamine concentration, ranging from 15 – 500 μg/mL, with a limit of detection (LOD of 2.0 μg/mL and a calibration sensitivity of 44.6 m° per log μg/mL histamine. Results also showed higher binding affinity of histamine for the MIP sensor than for the non-imprinted (NIP sensor indicating excellent specificity. Moreover, the selectivity of the MIP histamine sensor against some of its structural analogues was demonstrated.

  12. Excitatory effect of histamine on neuronal activity of rat cerebellar fastigial nucleus in vitro

    Institute of Scientific and Technical Information of China (English)

    TANG Biao; ZHANG Jun; LI HongZhao; ZHU JingNing; WANG JianJun

    2007-01-01

    The cerebellar fastigial nucleus (FN) holds an important role in motor control and body balance. Previous studies have revealed that the nucleus is innervated by direct hypothalamocerebellar histaminergic fibers. However, the functional role of histaminergic projection in cerebellar FN has never been established. In this study, we investigated the effect of histamine on neuronal firing of cerebellar FN by using slice preparations. Sixty-five FN cells were recorded from 47 cerebellar slices, and a vast majority of the cells responded to histamine stimulation with an excitatory response (58/65, 89.2%). Perfusing slices with low-Ca2+/high-Mg2+ medium did not block the histamine-induced excitation (n=10), supporting a direct postsynaptic action of histamine on the cells. Furthermore, the excitatory effect of histamine on FN neurons was not blocked by selective histamine H1 receptor antagonist triprolidine (n=15) or chlorpheniramine (n=10), but was effectively suppressed by ranitidine (n=15), a highly selective histamine H2 receptor antagonist. On the other hand, highly selective histamine H2 receptor agonist dimaprit (n=20) instead of histamine H1 receptor agonist 2-pyridylethylamine (n=16) mimicked the excitatory effect of histamine on FN neurons. The dimaprit-induced FN neuronal excitation was effectively antagonized by selective histamine H2 receptor antagonist ranitidine (n=13) but not influenced by selective histamine H1 receptor antagonist triprolidine (n=15). These results demonstrate that histamine excites cerebellar FN cells via the histamine H2 receptor mechanism and suggest that the hypothalamocerebellar histaminergic fibers may modulate cerebellar FN-mediated sensorimotor integration through their excitatory innervations on FN neurons.

  13. Histamine in hemorrhagic shock - A new approach with microdialysis

    NARCIS (Netherlands)

    Raum, M; Nagelschmidt, M; Rixen, D; Keiser, F; Gregor, S; Tiling, T; Bouillon, B; Neugebauer, E; Redl, H

    2005-01-01

    Microdialysis is a new approach for monitoring after hemorrhagic shock. The advantage of microdialysis is the local measurement of microcirculation and local changes of mediators. Until now this was mostly used in neuromonitoring. In this experiment we were focussed on the local changes of histamine

  14. Histamine receptors and antihistamines: from discovery to clinical applications.

    Science.gov (United States)

    Cataldi, Mauro; Borriello, Francesco; Granata, Francescopaolo; Annunziato, Lucio; Marone, Gianni

    2014-01-01

    The synthesis and the identification of histamine marked a milestone in both pharmacological and immunological research. Since Sir Henry Dale and Patrick Laidlaw described some of its physiological effects in vivo in 1910, histamine has been shown to play a key role in the control of gastric acid secretion and in allergic disorders. Using selective agonists and antagonists, as well as molecular biology tools, four histamine receptors (H1R, H2R, H3R and H4R) have been identified. The Nobel Prize in Physiology and Medicine was awarded to Daniel Bovet in 1957 for the discovery of antihistamines (anti-H1R) and to Sir James Black in 1988 for the identification of anti-H2R antagonists. Anti-H1R and anti-H2R histamine receptor antagonists have revolutionized the treatment of certain allergic disorders and gastric acid-related conditions, respectively. More recently, anti-H3R antagonists have entered early-phase clinical trials for possible application in obesity and a variety of neurologic disorders. The preferential expression of H4R by several immune cells and its involvement in the development of allergic inflammation provide the rationale for the use of anti-H4R antagonists in allergic and in other immune-related disorders.

  15. Histamine and neuroinflammation: insights from mouse experimental autoimmune encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Maria Beatrice ePassani

    2012-05-01

    Full Text Available Multiple sclerosis (MS is a chronic inflammatory, neurodegenerative disease of the CNS whose pathogenesis remains largely unknown, and available therapies are rarely successful in reversing neurological deficits or stopping disease progression. Ongoing studies on MS and the widely used murine model experimental autoimmune encephalomyelitis (EAE are trying to dissect out the many components of this complex and heterogeneous neurodegenerative disease in the hope of providing a mechanism-based characterization of MS that will afford successful strategies to limit and repair the neuronal damage. Recently, histamine has been postulated to have a key regulatory role in EAE and in MS pathogenesis. Histamine is a mediator of inflammation and immune responses, it explicates its many actions through four G protein-coupled receptors (H1,2,3,4R that signal through distinct intracellular pathways and have different therapeutic potentials as they vary in expression, distribution of isoforms, signaling properties and function. Immune cells involved in MS/EAE, including dendritic cells and T lymphocytes, express H1R, H2R and H4R, and histamine may have varying and counteracting effects on a particular cell type depending on the receptor subtypes being activated. Here, we review evidence of the complex and controversial role of histamine in MS/EAE pathogenesis and evaluate the therapeutic potential of histaminergic ligands to treat autoimmune diseases.

  16. Conformational study of neutral histamine monomer and their vibrational spectra

    Science.gov (United States)

    Mukherjee, V.; Yadav, T.

    2016-08-01

    Molecular modeling and potential energy scanning of histamine molecule, which is an important neurotransmitter, with respect to the dihedral angle of methylamine side chain have done which prefer three different conformers of histamine monomer. We have calculated molecular structures and vibrational spectra with IR and Raman intensities of these conformers using Density Functional Theory (DFT) with the exchange functional B3LYP incorporated with the basis set 6-31 ++G(d,p) and Hartree-Fock (HF) with the same basis set. We have also employed normal coordinate analysis (NCA) to scale the theoretical frequencies and to calculate potential energy distributions (PEDs) for the conspicuous assignments. Normal modes assignments of some of the vibrational frequencies of all the three conformers are in good agreement with the earlier reported experimental frequencies of histamine whereas others have modified. The standard deviations between the theoretical and experimental frequencies fall in the region 13-20 cm- 1 for the three conformers. NBO analyses of histamine conformers were also performed. The net charge transfers from ethylamine side chain to the imidazole ring. The intensive interactions between bonding and anti-bonding orbitals are found in imidazole ring. The HOMO-LUMO energy gap is nearly 5.50 eV.

  17. 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'.

  18. Matrix metalloproteinases-2/9-sensitive peptide-conjugated polymer micelles for site-specific release of drugs and enhancing tumor accumulation: preparation and in vitro and in vivo evaluation

    Directory of Open Access Journals (Sweden)

    Zhang X

    2016-04-01

    Full Text Available Xiaoyan Zhang, Xiaofei Wang, Weitong Zhong, Xiaoqing Ren, Xianyi Sha, Xiaoling FangKey Laboratory of Smart Drug Delivery, Ministry of Education and People’s Liberation Army of China, School of Pharmacy, Fudan University, Shanghai, People’s Republic of China Abstract: Since elevated expression of matrix metalloproteinase (MMP-2 and MMP-9 is commonly observed in several malignant tumors, MMPs have been widely reported as key factors in the design of drug delivery systems. Several strategies have been proposed to develop MMPs-responsive nanoparticles to deliver chemotherapeutics to malignant solid tumors. A stimuli-responsive drug delivery system, which could be cleaved by MMPs, was proposed in this study. By inserting an MMP-2/9 cleavable oligopeptide GPVGLIGK-NH2 (GK8 as spacer between α-tocopherol succinate (α-TOS and methoxy-polyethylene glycol molecular weight (MW 2000 Da activated by N-hydroxysuccinimide (mPEG2K-NHS, mPEG2K-GK8-α-TOS (TGK was synthesized as the primary ingredient for MMP-2/9-sensitive micelles composed of D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS and TGK (n:n =40:60, TGK micelles. mPEG2K-α-TOS (T2K was similarly synthesized as nonsensitive control. The TGK micelles showed better stability than nonsensitive micelles composed of TPGS and T2K (n:n =40:60, T2K micelles owing to the inserted peptide. Fluorescence resonance energy transfer results indicated that TGK micelles could be successfully cleaved by MMP-2/9. Effective drug release was demonstrated in the presence of collagenase type IV, a mixture of MMP-2 and MMP-9. Compared with nonsensitive micelles, docetaxel (DTX-loaded TGK micelles showed a fold higher cellular uptake in HT1080 cells. While the half-maximal inhibitory concentration (IC50 of TGK and T2K micelles were similar (P>0.05 in MCF-7 cells (MMP-2/9 underexpression, the IC50 values of the aforementioned micelles were 0.064±0.006 and 0.122±0.009 µg/mL, respectively, in HT1080 cells (MMP

  19. Proposal of employ of extract of Desmodium adscendens as anti-histaminic natural drug: trials of efficacy by Reflectance Spectrophotometry

    Directory of Open Access Journals (Sweden)

    Lorenzo Martini

    2014-01-01

    manifestation twice a day for one week: at 09.00 a.m. (to check the gravity of erythema induced in each single case and at 04.30 p.m., to check the real efficacy of the D.A. hydroglyceric extract. We have to keep seriously on account that Reflectance Spectrophotoscopy can’t evaluate histamine concentration and its characteristic effects and that the 40–50% of cases of erythematous manifestations are not rigorously ascribable to the phenomenon of the histamine release. Results and Conclussions: Results are amazingly encouraging, since it has been observed that the mean value of the blanching effect of the electuary on erythema is of 48.8%.

  20. New aspects of the role of histamine in cardiovascular function: identification, characterization, and potential pathophysiological importance of H3 receptors.

    Science.gov (United States)

    Göthert, M; Garbarg, M; Hey, J A; Schlicker, E; Schwartz, J C; Levi, R

    1995-05-01

    As a result of intensive research during several decades, the distribution, function, and pathophysiological role of cardiovascular H1 and H2 receptors are well known, whereas reports on the occurrence and function of H3 receptors in blood vessels and the heart have not become available before the last 7 years (i.e., 4 years after the first description of these receptors in the central nervous system in 1983). The development of selective and potent H3 receptor agonists and antagonists was a prerequisite for convenient investigations of cardiovascular H3 receptors, which like H1 and H2 receptors are G-protein coupled but unlike them have not yet been cloned. Both in blood vessels and the heart, H3 receptors are located on noradrenergic nerve endings and upon stimulation mediate an inhibition of noradrenaline release. Whereas it remains to be clarified under which conditions the vascular H3 receptors may be stimulated by endogenous histamine, those in the heart become activated in the early phases of myocardial ischemia characterized by an increased histamine spillover. The H3 receptors in the central nervous system also appear to be of importance for the control of vascular function. Inhibitory presynaptic H3 receptors occur on trigeminal sensory C fibres supplying blood vessels in the dura mater. Release of neuropeptides from these fibres induces a neurogenic inflammation, which has been suggested to be involved in the pathogenesis of migraine. An interaction, involving presynaptic H3 receptors, between sensory C fibres and mast cells in close apposition to these fibres plays a role in the control of histamine synthesis in the dura mater.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. A single dose of histamine-receptor antagonists before downhill running alters markers of muscle damage and delayed-onset muscle soreness.

    Science.gov (United States)

    Ely, Matthew R; Romero, Steven A; Sieck, Dylan C; Mangum, Joshua E; Luttrell, Meredith J; Halliwill, John R

    2017-03-01

    histamine's actions attenuated muscle strength loss and reduced perceptions of muscle pain for 72 h following muscle-damaging exercise. These results indicate that exercise-induced histamine release may have a broad impact on protecting muscle from exercise-induced damage.

  2. Pharmacological Characterization of Human Histamine Receptors and Histamine Receptor Mutantsin the Sf9 Cell Expression System.

    Science.gov (United States)

    Schneider, Erich H; Seifert, Roland

    2017-02-24

    A large problem of histamine receptor research is data heterogeneity. Various experimental approaches, the complex signaling pathways of mammalian cells, and the use of different species orthologues render it difficult to compare and interpret the published results. Thus, the four human histamine receptor subtypes were analyzed side-by-side in the Sf9 insect cell expression system, using radioligand binding assays as well as functional readouts proximal to the receptor activation event (steady-state GTPase assays and [(35)S]GTPγS assays). The human H1R was co-expressed with the regulators of G protein signaling RGS4 or GAIP, which unmasked a productive interaction between hH1R and insect cell Gαq. By contrast, functional expression of the hH2R required the generation of an hH2R-Gsα fusion protein to ensure close proximity of G protein and receptor. Fusion of hH2R to the long (GsαL) or short (GsαS) splice variant of Gαs resulted in comparable constitutive hH2R activity, although both G protein variants show different GDP affinities. Medicinal chemistry studies revealed profound species differences between hH1R/hH2R and their guinea pig orthologues gpH1R/gpH2R. The causes for these differences were analyzed by molecular modeling in combination with mutational studies. Co-expression of the hH3R with Gαi1, Gαi2, Gαi3, and Gαi/o in Sf9 cells revealed high constitutive activity and comparable interaction efficiency with all G protein isoforms. A comparison of various cations (Li(+), Na(+), K(+)) and anions (Cl(-), Br(-), I(-)) revealed that anions with large radii most efficiently stabilize the inactive hH3R state. Potential sodium binding sites in the hH3R protein were analyzed by expressing specific hH3R mutants in Sf9 cells. In contrast to the hH3R, the hH4R preferentially couples to co-expressed Gαi2 in Sf9 cells. Its high constitutive activity is resistant to NaCl or GTPγS. The hH4R shows structural instability and adopts a G protein-independent high

  3. Effects of histamine on 5-hydroxytryptaminergic neuronal activity in the rat hypothalamus.

    Science.gov (United States)

    Fleckenstein, A E; Lookingland, K J; Moore, K E

    1994-03-11

    Effects of pharmacological manipulations which mimic or enhance histaminergic neuronal transmission were determined on the activity of 5-hydroxytryptaminergic neurons projecting to the hypothalamus of male rats. Intracerebroventricular administration of histamine decreased 5-hydroxytryptamine (5-HT) and increased 5-hydroxyindoleacetic acid (5-HIAA) concentrations in several hypothalamic nuclei; these effects were blocked by the histamine H1 receptor antagonist mepyramine but not the histamine H2 receptor antagonist zolantidine. Blockade of the 5-HT reuptake system by fluoxetine did not prevent histamine-induced decreases in 5-HT concentrations suggesting that histamine is not transported into nerve terminals via the 5-HT reuptake system to subsequently displace 5-HT stores. These data suggest that exogenous histamine increases 5-hydroxytryptaminergic neuronal activity through an action at histamine H1 receptors. In contrast, neither the histamine H3 receptor antagonist thioperamide, the histamine-N-methyltransferase inhibitor metoprine, nor combined thioperamide-metoprine treatment affected concentrations of 5-HT or 5-HIAA suggesting these agents, which purportedly enhance endogenous histaminergic transmission, do not affect 5-hydroxytryptaminergic neuronal activity. These results reveal that procedures commonly employed to study central actions of histamine differentially affect 5-hydroxytryptaminergic neuronal activity in the rat hypothalamus.

  4. Determination of histamine in canned tuna by molecularly imprinted polymers-surface enhanced Raman spectroscopy.

    Science.gov (United States)

    Gao, Fang; Grant, Edward; Lu, Xiaonan

    2015-12-11

    We introduce a rapid, cost effective and reliable approach to determine histamine level in canned tuna. Molecularly imprinted polymers (MIPs) were synthesized as artificial antibodies towards histamine by utilizing the interaction between histamine and a functional monomer (methacrylic acid) to impress specific binding sites on polymer particles after polymerization. Polyvinyl chloride (PVC) was used to immobilize the MIPs, yielding a MIPs-PVC film that functioned as a recognition element to specifically separate histamine from tuna extract. A gold colloid solution served both as an eluting solvent to extract histamine from MIPs-PVC film and furnish a substrate for surface enhanced Raman spectroscopy (SERS) detection of histamine signals. Principal component analysis together with a partial least square regression (PLSR) model (R(2) = 0.947, RMSECV = 3.526) verified the reliability of MIPs-PVC-SERS approach for the detection and spectral analysis of histamine. Linear regression models were also constructed to relate the intensity of different histamine SERS bands with the corresponding spiking levels. One such model (using a band at 1576 cm(-1)) performed slightly better in predicting histamine content in tuna than the PLSR model. We conclude that our new MIPs-PVC-SERS approach can rapidly and reliably determine histamine at levels from 3 to 90 ppm in canned tuna meat.

  5. Lactobacillus casei strains isolated from cheese reduce biogenic amine accumulation in an experimental model.

    Science.gov (United States)

    Herrero-Fresno, Ana; Martínez, Noelia; Sánchez-Llana, Esther; Díaz, María; Fernández, María; Martin, Maria Cruz; Ladero, Victor; Alvarez, Miguel A

    2012-07-02

    Tyramine and histamine are the biogenic amines (BAs) most commonly found in cheese, in which they appear as a result of the microbial enzymatic decarboxylation of tyrosine and histidine respectively. Given their toxic effects, their presence in high concentrations in foods should be avoided. In this work, samples of three cheeses (Zamorano, Cabrales and Emmental) with long ripening periods, and that often have high BA concentrations, were screened for the presence of BA-degrading lactic acid bacteria (LAB). Seventeen isolates were found that were able to degrade tyramine and histamine in broth culture. All 17 isolates were identified by 16S rRNA sequencing as belonging to Lactobacillus casei. They were typed by plasmid S1-PFGE and genomic macrorestriction-PFGE analysis. Two strains (L. casei 4a and 5b) associated with high degradation rates for both BAs were selected to test how this ability might affect histamine and tyramine accumulation in a Cabrales-like mini-cheese manufacturing model. The quantification of BAs and the monitoring of the strains' growth over ripening were undertaken by RP-HPLC and qPCR respectively. Both strains were found to reduce histamine and tyramine accumulation. These two strains might be suitable for use as adjunct cultures for reducing the presence of BAs in cheese.

  6. Effects of high levels of dietary zinc oxide on ex vivo epithelial histamine response and investigations on histamine receptor action in the proximal colon of weaned piglets.

    Science.gov (United States)

    Kröger, S; Pieper, R; Aschenbach, J R; Martin, L; Liu, P; Rieger, J; Schwelberger, H G; Neumann, K; Zentek, J

    2015-11-01

    The aim of the study was to identify the effect of high dietary zinc oxide (ZnO) levels on the histamine-induced secretory-type response and histamine metabolism in the porcine proximal colon. After weaning at d 26, 3 diets with low (LZn), normal (NZn), and high (HZn) concentrations of zinc (57, 164, or 2,425 mg/kg) were fed to a total of 120 piglets. Digesta and tissue samples were taken from the ascending colon after 7 ± 1, 14 ± 1, 21 ± 1, and 28 ± 1 d. Partially stripped tissue was mounted in Ussing chambers, and histamine was applied either to the serosal or mucosal compartments. Tissue was pretreated with or without aminoguanidine and amodiaquine to block the histamine-degrading enzymes diamine oxidase (DAO) and histamine -methyltransferase (HMT), respectively. Gene expression and catalytic activity of DAO and HMT in the tissue were analyzed. The numbers of mast cells were determined in tissue samples, and histamine concentration was measured in the colon digesta. Colon tissue from another 12 piglets was used for functional studies on histamine H and H receptors by using the neuronal conduction blocker tetrodotoxin (TTX) and the H and H receptor blocker chloropyramine and famotidine, respectively. After serosal histamine application to colonic tissue in Ussing chambers, the change of short-circuit current (Δ) was not affected by pretreatment and was not different between Zn feeding groups. The Δ after mucosal histamine application was numerically lower ( = 0.168) in HZn compared to LZn and NZn pigs. Mast cell numbers increased from 32 to 46 d of life ( histamine response was partly inhibited by chloropyramine or famotidine ( histamine tended to be decreased when chloropyramine but not famotidine was applied from either the serosal or the mucosal side ( = 0.055). Tetrodotoxin alone or in combination with chloropyramine resulted in a similar reduction in the mucosal histamine response ( histamine metabolism on dietary ZnO oversupplementation. For the first

  7. Sleep and waking during acute histamine H3 agonist BP 2.94 or H3 antagonist carboperamide (MR 16155) administration in rats.

    Science.gov (United States)

    Monti, J M; Jantos, H; Ponzoni, A; Monti, D

    1996-07-01

    The present study evaluated the effects of histamine H3 receptor agonist BP 2.94 or H3 receptor antagonist carboperamide (MR 16155) given by oral route on sleep and waking in rats surgically prepared for long-term recordings. BP 2.94 produced a significant increase of slow-wave sleep (SWS) that was related to slight decreases of waking, light sleep, and REM sleep. Carboperamide significantly increased waking and decreased SWS and REM sleep. Pretreatment with carboperamide prevented the effect of BP 2.94 on SWS. It is suggested that the effects of BP 2.94 or carboperamide on sleep and waking could depend on changes in the availability of histamine at the postsynaptic H1 receptor. Alternatively, activation or blockade of the H3 heteroreceptors found in the central catecholamine, indolamine, and acetylcholine nerve endings could inhibit or increase the release of noradrenaline, serotonin, dopamine, and acetylcholine. This would secondarily result in changes of sleep variables.

  8. The interaction between histamine H1 receptor and μ- opioid receptor in scratching behavior in ICR mice.

    Science.gov (United States)

    Nakasone, Tasuku; Sugimoto, Yumi; Kamei, Chiaki

    2016-04-15

    In this study, we examined the interaction between histamine H1 receptor and μ-opioid receptor in scratching behavior in ICR mice. Both histamine and morphine caused scratching and simultaneous injection of histamine and morphine had an additive effect. Chlorpheniramine and naloxone inhibited histamine-induced scratching behavior. These two drugs also inhibited morphine-induced scratching behavior. Simultaneous injection of chlorpheniramine and naloxone caused a significant inhibition of histamine-induced scratching compared with separate injections. The same findings were also noted for morphine-induced scratching. These results strongly indicate a close relationship between histamine H1 receptor and μ-opioid receptor in scratching behavior in ICR mice.

  9. Analysis of histamine receptors in the central thermoregulatory mechanism of Mastomys natalensis.

    OpenAIRE

    Dhawan, B. N.; Shukla, R.; Srimal, R. C.

    1982-01-01

    1 The effect of intracerebroventricular (i.c.v.) injection of histamine on the rectal temperature of Mastomys natalensis at ambient temperatures of 10, 24 and 33 degrees C has been studied. 2 Low doses (0.1-1.0 microgram) of histamine produced hypothermia while larger doses (5-20 micrograms) produced dose-dependent hyperthermia. The hypothermic effect was significantly antagonized by mepyramine while the hyperthermia was blocked by cimetidine. 3 Histamine H1-receptor agonists, 2-methyl-histam...

  10. Development of molecular approach based on PCR assay for detection of histamine producing bacteria.

    Science.gov (United States)

    Wongsariya, Karn; Bunyapraphatsara, Nuntavan; Yasawong, Montri; Chomnawang, Mullika Traidej

    2016-01-01

    Histamine fish poisoning becomes highly concern not only in public health but also economic aspect. Histamine is produced from histidine in fish muscles by bacterial decarboxylase enzyme. Several techniques have been developed to determine the level of histamine in fish and their products but the effective method for detecting histamine producing bacteria is still required. This study was attempted to detect histamine producing bacteria by newly developed PCR condition. Histamine producing bacteria were isolated from scombroid fish and determined the ability to produce histamine of isolated bacteria by biochemical and TLC assays. PCR method was developed to target the histidine decarboxylase gene (hdc). The result showed that fifteen histamine producing bacterial isolates and three standard strains produced an amplicon at the expected size of 571 bp after amplified by PCR using Hdc_2F/2R primers. Fifteen isolates of histamine producing bacteria were classified as M. morganii, E. aerogenes, and A. baumannii. The lowest detection levels of M. morganii and E. aerogenes were 10(2) and 10(5) Cfu/mL in culture media and 10(3) and 10(6) Cfu/mL in fish homogenates, respectively. The limit of detection by this method was clearly shown to be sensitive because the primers could detect the presence of M. morganii and E. aerogenes before the histamine level reached the regulation level at 50 ppm. Therefore, this PCR method exhibited the potential efficiency for detecting the hdc gene from histamine producing bacteria and could be used to prevent the proliferation of histamine producing bacteria in fish and fish products.

  11. Punishing and cardiovascular effects of intravenous histamine in rats: pharmacological selectivity.

    Science.gov (United States)

    Podlesnik, Christopher A; Jimenez-Gomez, Corina

    2013-11-01

    Although drugs may serve as reinforcers or punishers of operant behavior, the punishing function has received much less experimental attention than the reinforcing function. A sensitive method for studying drug-induced punishment is to assess choice for a punished response over an unpunished response. In these experiments, rats chose between pressing one lever and receiving a sucrose pellet or pressing another lever and receiving a sucrose pellet plus an intravenous injection of histamine. When sucrose was delivered equally frequently for either the punished or the unpunished response, rats selected the unpunished lever consistently, but decreases in the punished response did not differ as a function of intravenous histamine dose (0.1-1 mg/kg/inj). Changing the procedure so that sucrose was delivered on the unpunished lever with p = .5 increased the rats' responding on the punished lever with saline injections. In addition, the same range of histamine doses produced a much larger range of responses on the punished lever that was dose dependent. Using these procedures to assess the receptors mediating histamine's effects, the histamine H1 -receptor antagonists, pyrilamine and ketotifen, antagonized the punishing effect of histamine, but the histamine H2 -receptor antagonist ranitidine did not. However, ranitidine pretreatments reduced histamine-induced heart-rate increases to a greater extent than did the histamine H1 -receptor antagonists when administered at the same doses examined under conditions of histamine punishment. Overall, the present findings extend the general hypothesis that activation of histamine H1 -receptors mediates the punishing effects of histamine. They also introduce methods for rapidly assessing pharmacological mechanisms underlying drug-induced punishment.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1982-08-01

    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 /sup 3/H-1-methylhistamine (generated by the enzyme N-methyltransferase acting on histamine in the presence of S-(methyl-/sup 3/H)-adenosyl-L-methionine) into chloroform and isolating the /sup 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.

  13. [Prick tests for histamine and cow milk in children].

    Science.gov (United States)

    Ruiz, F J; Jiménez, A

    1995-01-01

    Three hundred and one children were evaluated in six different rural areas in Tlaxcala, State (México). Through skin prick tests which included histamine, glycerine, cow's milk antigen and a drop fulfill a registration form including: personal data; personal and family atopic background; degree and frequency of gastrointestinal, respiratory and cutaneous diseases, as well as the child temperament. Besides, feeding history (length and type of breast-feeding). Six cases were found positive to cow's milk antigen (1.9%) by Prick test but none of them had showed signology related to (83%) were breast-fed at least for the first month of life. Histamine wheal size increased progressively up to eight months of age and reached a plateau.

  14. Spectrofluorometric determination of histamine in wines and other alcoholic beverages.

    Science.gov (United States)

    Vidal-Carou, M C; Izquierdo-Pulido, M L; Mariné-Font, A

    1989-01-01

    The spectrofluorometric determination of histamine in wines, other alcoholic beverages, and vinegars is described. Histamine is extracted with n-butanol, transferred to hydrochloric acid, and subjected to a condensation reaction with o-phthalaldehyde (OPT). The method was tested for sensitivity (0.03 ppm limit of detection and 0.08 ppm limit of determination), precision (6.4% CV for a content of 1.25 ppm and 19.5% CV for a content of 0.25 ppm), accuracy (97.1%), recovery (90.6-96.9%), and lack of interference by histidine. The method can be applied to wine, must, beer, champagne, cider, vermouth, and vinegar with satisfactory results.

  15. Histamine and tyramine degradation by food fermenting microorganisms.

    Science.gov (United States)

    Leuschner, R G; Heidel, M; Hammes, W P

    1998-01-06

    Microorganisms suitable for food fermentation were examined with regard to their potential to degrade histamine and tyramine. Out of 64 lactic acid bacteria evaluated in this study, 27 degraded histamine and one tyramine, respectively, with low activity. Among 32 strains of Brevibacterium linens and coryneform bacteria, 21 exhibited histamine and tyramine oxidase activity. None of 20 strains of Staphylococcus carnosus tested degraded histamine or tyramine. One strain out of nine strains of Geotrichum candidum degraded tyramine slightly. Among 44 strains of Micrococcus sp. examined, 17 degraded either one or two biogenic amines. In this study Micrococcus varians (M. varians) LTH 1540 exhibited the highest tyramine oxidase activity of all strains tested and was therefore investigated in detail. The enzyme was found to be located in the cytoplasm and was not membrane bound. The reaction end product p-hydroxyphenyl acetic acid was detected by HPLC analysis. An activity staining for the amine oxidase in a native polyacrylamide gel based on the formation of H2O2 during amine oxidation was developed. Resting cells of the strain exhibited optimal tyramine oxidase activity at a pH of 7 at 37-40 degrees C. The enzyme in the cell free extract had a pH optimum between 7-8. The enzyme activity was decreased by NaCl, glucose and hydralazine. Phenylethylamine and tryptamine were oxidized at lower concentrations than tyramine. The potential for amine degradation was not found to be associated with that of formation of biogenic amines, as 23 microorganisms with the ability to metabolise biogenic amines exhibited no decarboxylase activity toward histidine, tyrosine, phenylalanine, lysine or ornithine.

  16. Effects of histamine and cholinergic systems on memory retention of passive avoidance learning in rats.

    Science.gov (United States)

    Eidi, Maryam; Zarrindast, Mohammad-Reza; Eidi, Akram; Oryan, Shahrbanoo; Parivar, Kazem

    2003-03-28

    In the present study, the effects of the histamine and cholinergic systems on memory retention in adult male rats were investigated. Post-training intracerebroventricular injections were carried out in all the experiments. Cholinoceptor agonist, acetylcholine (1-10 microg/rat) or nicotine (1-10 microg/rat), increased, while a cholinoceptor antagonist, scopolamine (5-20 microg/rat), decreased memory retention. The response to acetylcholine was attenuated by scopolamine. Administration of histamine (5-20 microg/rat) reduced, but the histamine H(1) receptor antagonist, pyrilamine (10-50 microg/rat), and the histamine H(2) receptor antagonist, cimetidine (1-50 microg/rat), increased memory retention in rats. The histamine receptor antagonists attenuated the response to histamine. Histamine reduced the acetylcholine- or nicotine-induced enhancement. The histamine receptor antagonists enhanced the nicotine- or acetylcholine-induced response. Histamine potentiated the inhibitory effect induced by scopolamine. It is concluded that histaminergic and cholinergic systems have opposing effects on memory retention. Also, the histaminergic system elicits an interaction with the cholinergic system in memory retention.

  17. Hippocampal somatostatin receptors and modulation of adenylyl cyclase activity in histamine-treated rats

    OpenAIRE

    Puebla Jiménez, Lilian; Rodríguez Martín, Eulalia; Arilla Ferreiro, Eduardo

    1996-01-01

    In the present study, the effects of an intracerebroventricular (i.c.v.) dose of histamine (0.1, 1.0 or 10.0 ¿g) on the hippocampal somatostatin (SS) receptor/effector system in Wistar rats were investigated. In view of the rapid onset of histamine action, the effects of histamine on the somatostatinergic system were studied 2 h after its administration. Hippocampal SS-like immunoreactivity (SSLI) levels were not modified by any of the histamine doses studied. SS-mediated inhibition of basal ...

  18. 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.

  19. Quality control of the analysis of histamine in fish by proficiency test

    Science.gov (United States)

    Evangelista, Warlley P.; Tette, Patrícia A. S.; Gloria, Maria Beatriz A.

    2015-01-01

    The analysis of histamine is required by the European Union for the importation of tuna and other Scombroid fish. The aim of this study was to investigate the quality of the analysis of histamine in fish, by means of reference material (RM) and of proficiency test (PT). Sample analysis carried out using RM provided 89.4% recovery. During the proficiency test, the histamine content of the sample was 311.9 mg/kg and the z-score was zero. These results assure the good performance of the laboratory in the analysis of histamine in fish, asuring reliability of results to clients.

  20. Aggravated myocardial infarction-induced cardiac remodeling and heart failure in histamine-deficient mice

    Science.gov (United States)

    Chen, Jinmiao; Hong, Tao; Ding, Suling; Deng, Long; Abudupataer, Mieradilijiang; Zhang, Weiwei; Tong, Minghong; Jia, Jianguo; Gong, Hui; Zou, Yunzeng; Wang, Timothy C.; Ge, Junbo; Yang, Xiangdong

    2017-01-01

    Histamine has pleiotropic pathophysiological effects, but its role in myocardial infarction (MI)-induced cardiac remodeling remains unclear. Histidine decarboxylase (HDC) is the main enzyme involved in histamine production. Here, we clarified the roles of HDC-expressing cells and histamine in heart failure post-MI using HDC-EGFP transgenic mice and HDC-knockout (HDC−/−) mice. HDC+CD11b+ myeloid cell numbers markedly increased in the injured hearts, and histamine levels were up-regulated in the circulation post-MI. HDC−/− mice exhibited more adverse cardiac remodeling, poorer left ventricular function and higher mortality by increasing cardiac fibrogenesis post-MI. In vitro assays further confirmed that histamine inhibited heart fibroblast proliferation. Furthermore, histamine enhanced the signal transducer and activator of transcription (STAT)-6 phosphorylation level in murine heart fibroblasts, and the inhibitive effects of histamine on fibroblast proliferation could be blocked by JAK3/STAT6 signaling selective antagonist. STAT6-knockout (STAT6−/−) mice had a phenotype similar to that of HDC−/− mice post-MI; however, in contrast to HDC−/− mice, the beneficial effects of exogenous histamine injections were abrogated in STAT6−/− mice. These data suggest that histamine exerts protective effects by modulating cardiac fibrosis and remodeling post-MI, in part through the STAT6-dependent signaling pathway. PMID:28272448

  1. Roles of histamine on the expression of aldehyde dehydrogenase 1 in endometrioid adenocarcinoma cell line.

    Science.gov (United States)

    Wang, Yi; Jiang, Yang; Ikeda, Jun-Ichiro; Tian, Tian; Sato, Atsushi; Ohtsu, Hiroshi; Morii, Eiichi

    2014-10-01

    Cancer-initiating cells (CICs) are a limited number of cells that are essential for maintenance, recurrence, and metastasis of tumors. Aldehyde dehydrogenase 1 (ALDH1) has been recognized as a marker of CICs. We previously reported that ALDH1-high cases of uterine endometrioid adenocarcinoma showed poor prognosis, and that ALDH1 high population was more tumorigenic, invasive, and resistant to apoptosis than ALDH1 low population. Histamine plays a critical role in cancer cell proliferation, migration, and invasion. Here, we examined the effect of histamine on ALDH1 expression in endometrioid adenocarcinoma cell line. The addition of histamine increased ALDH1 high population, which was consistent with the result that histamine enhanced the invasive ability and the resistance to anticancer drug. Among 4 types of histamine receptors, histamine H1 and H2 receptor (H1R and H2R) were expressed in endometrioid adenocarcinoma cell line. The addition of H1R agonist but not H2R agonist increased ALDH1. The antagonist H1R but not H2R inhibited the effect of histamine on ALDH1 expression. These results indicated that histamine increased the expression of ALDH1 via H1R but not H2R. These findings may provide the evidence for exploring a new strategy to suppress CICs by inhibiting ALDH1 expression with histamine.

  2. Role of histamine H1-and H2-receptors in the cardiovascular system of the rabbit.

    Science.gov (United States)

    Sakai, K

    1980-01-01

    The effects of histamine were examined on the circulation of the blood-perfused heart, kidney, intestine, and hindlimb of rabbits. Single intrarterial injections of drugs were made into the perfusion system of the coronary, renal, mesenteric, or femoral vascular bed. In the hearts, histamine caused dose-dependent positive inotropic and chronotropic responses and vaso-constriction. 2-Methylhistamine, a relatively selective histamine H1-receptor agonist, produced vascular effects very similar to those of histamine, but had no cardiac actions at low and negative inotropic responses at high doses. 4-Methylhistamine, a relatively selective histamine H2-receptor agonist, induced slight vasodilatation and positive inotropic and chronotropic responses. In the renal, mesenteric, and femoral vascular beds, histamine and 2-methylhistamine caused vasoconstriction, while 4-methylhistamine induced slight vasodilatation. Mepyramine, a selective H1-receptor antagonist, blocked the vasoconstriction in response to histamine and 2-methylhistamine, but not the positive inotropic and chronotropic responses to histamine. The combined action of mepyramine and cimetidine (a selective H2-receptor antagonist) eliminated all cardiac and vascular effects of histamine. These results strongly support the view that in the cardiovascular system of the rabbit, H1-receptors mediate negative inotropic effects and vasoconstriction, whereas H2-receptors are responsible for positive inotropic and chronotropic effects and vasodilatation.

  3. Identification and specific blockade of two receptors for histamine in the cardiovascular system.

    Science.gov (United States)

    Powell, J R; Brody, M J

    1976-01-01

    Histamine caused a fall in blood pressure in anesthetized dogs and cats which was only partially attenuated by mepyramine (pyrilamine), a histamine type H1-receptor antagonist. Further treatment with burimide or metiamide, type H2-receptor antagonists, caused nearly complete attenuation of the response to histamine. Burimamide alone had no effect on vasodilatation produced by histamine in the dog gracilis muscle whereas mepyramine alone caused a partial attenuation. An H2-receptor agonist, 4-methylhistamine and an H1-receptor agonist, 2-(2-pyridyl)ethylamine, both produced vasodilatation which was blocked by metiamide and mepyramine, respectively. Constriction of the saphenous vein produced by histamine was found to involve interaction with H1-receptors only. In the intact dog, histamine increased heart rate and decreased left ventricular dp/dt through direct effects. Mepyramine prevented the increase in heart rate but did not affect the chronotropic actions of isoproterenol and glyceryl trinitrate. H1-receptor blockade did not alter inotropic effects whereas subsequent H2-receptor blockade prevented the negative inotropic effect of histamine. It is concluded that both peripheral vascular and cardiac responses to histamine are mediated through activation of H1- and H2-histamine receptors.

  4. Neuronal histamine and the interplay of memory, reinforcement and emotions.

    Science.gov (United States)

    Dere, E; Zlomuzica, A; De Souza Silva, M A; Ruocco, L A; Sadile, A G; Huston, J P

    2010-12-31

    The biogenic amine histamine is an important neurotransmitter-neuromodulator in the central nervous system that has been implicated in a variety of biological functions including thermo- and immunoregulation, food intake, seizures, arousal, anxiety, reward and memory. The review of the pertinent literature indicates that the majority of findings are compatible with the appraisal that the inhibition of histaminergic neurotransmission impairs learning and memory formation, decreases cortical activation and arousal, has a suppressive effect on behavioral measures of fear and anxiety, exponentiates the rewarding effects of drugs of abuse and intracranial brain stimulation. In contrast, the stimulation of histaminergic neurotransmission can ameliorate learning and memory impairments that are associated with various experimental deficit models and pathological conditions. Clinical investigations with patients suffering from neurodegenerative diseases such as Alzheimer's and Parkinson's disease demonstrate pathological alterations in the brain's histaminergic system, which, in some cases are correlated with the severity of cognitive deficits. The role of the brain's histamine system in episodic memory formation and the potential of histamine-related drugs to ameliorate cognitive deficits in early stages of neurodegenerative diseases are discussed.

  5. Serotonin and Histamine Therapy Increases Tetanic Forces of Myoblasts, Reduces Muscle Injury, and Improves Grip Strength Performance of Dmdmdx Mice

    Directory of Open Access Journals (Sweden)

    Volkan Gurel

    2015-11-01

    Full Text Available Duchenne muscular dystrophy (DMD is a recessive X-linked fatal disorder caused by a mutation in the dystrophin gene. Although several therapeutic approaches have been studied, none has led to substantial long-term effects in patients. The aim of this study was to test a serotonin and histamine (S&H combination on human skeletal myoblasts and Dmdmdx mice for its effects on muscle strength and injury. Normal human bioartificial muscles (BAMs were treated, and muscle tetanic forces and muscle injury tests were performed using the MyoForce Analysis System. Dmdmdx mice, the murine model of DMD, were administered serotonin, histamine, or S&H combination twice daily for 6 weeks, and functional performance tests were conducted once a week. The S&H combination treatment caused significant increases in tetanic forces at all time points and concentrations tested as compared to the saline controls. Dose response of the BAMs to the treatment demonstrated a significant increase in force generation at all concentrations compared to the controls after 3 to 4 days of drug treatment. The highest 3 concentrations had a significant effect on lowering contractile-induced injury as measured by a reduction in the release of adenylate kinase. Histamine-only and S&H treatments improved grip strength of Dmdmdx mice, whereas serotonin-only treatment resulted in no significant improvement in muscle strength. The results of this study indicate that S&H therapy might be a promising new strategy for muscular dystrophies and that the mechanism should be further investigated.

  6. Associations of polymorphisms in histidine decarboxylase, histamine N-methyltransferase and histamine receptor H3 genes with breast cancer.

    Directory of Open Access Journals (Sweden)

    Gong-Hao He

    Full Text Available We previously found that genetic polymorphisms in gene coding for histamine H4 receptors were related to the risk and malignant degree of breast cancer. The roles of polymorphisms in other histamine-related genes, such as histidine decarboxylase (HDC, histamine N-methyltransferase (HNMT and histamine H3 receptor (HRH3, remain unexplored. The aim of this study is to analyze the clinical associations of polymorphisms in HDC, HNMT and HRH3 with breast cancer. Two hundred and one unrelated Chinese Han breast cancer patients and 205 ethnicity-matched health controls were recruited for case-control investigation. Genomic DNA from the participants was extracted and 5 single nucleotide polymorphisms (SNPs in HDC, HNMT and HRH3 were genotyped. We found that polymorphisms of HNMT and HRH3 were irrelevant with breast cancer in the present study. However, the T allele of rs7164386 in HDC significantly decreased the risk of breast cancer (adjusted odds ratios [ORs], 0.387; 95% confidence intervals [CIs], 0.208-0.720; P = 0.003. Furthermore, for HDC haplotypes, the CG haplotype of rs7164386-rs7182203 was more frequent among breast cancer patients (adjusted OR, 1.828; 95% CI, 1.218-2.744; P = 0.004 while the TG haplotype was more frequent among health controls (adjusted OR, 0.351; 95% CI, 0.182-0.678; P = 0.002. These findings indicated that polymorphisms of HDC gene were significantly associated with breast cancer in Chinese Han population and may be novel diagnostic or therapeutic targets for breast cancer. Further studies with larger participants worldwide are still needed for conclusion validation.

  7. Determination of histamine and 1-methylhistamine in human plasma by high-performance liquid chromatography and fluorescence detection

    NARCIS (Netherlands)

    Wubs KL; Stolker AAM; Kortboyer JM; Meulenbelt J; van Ginkel LA; ARO

    1997-01-01

    Voor de bepaling van histamine en 1-methylhistamine (=Nt-methylhistamine=histamine metaboliet) in humaanplasma is de vloeistofchromatografische methode gebruikt. De uit het plasma geextraheerde histaminen werden met behulp van fluorescamine gederivatiseerd tot fluorescerende verbindingen. De deriv

  8. Hippocampal somatostatin receptors and modulation of adenylyl cyclase activity in histamine-treated rats.

    Science.gov (United States)

    Puebla, L; Rodríguez-Martín, E; Arilla, E

    1996-01-01

    In the present study, the effects of an intracerebroventricular (i.c.v.) dose of histamine (0.1, 1.0 or 10.0 micrograms) on the hippocampal somatostatin (SS) receptor/effector system in Wistar rats were investigated. In view of the rapid onset of histamine action, the effects of histamine on the somatostatinergic system were studied 2 h after its administration. Hippocampal SS-like immunoreactivity (SSLI) levels were not modified by any of the histamine doses studied. SS-mediated inhibition of basal and forskolin (FK)-stimulated adenylyl cyclase (AC) activity was markedly increased in hippocampal membranes from rats treated with 10 micrograms of histamine (23% +/- 1% vs. 17% +/- 1% and 37% +/- 2% vs. 23% +/- 1%, respectively). In contrast, neither the basal nor the FK-stimulated enzyme activities were affected by histamine administration. The functional activity of the hippocampal guanine-nucleotide binding inhibitory protein (Gi protein), as assessed by the capacity of the stable GTP analogue 5'-guanylylimidodiphosphate (Gpp[NH]p) to inhibit FK-stimulated AC activity, was not modified by histamine administration. These data suggest that the increased response of the enzyme to SS was not related to an increased functional activity of Gi proteins. In fact, the increased AC response to SS in hippocampal membranes from histamine (10 micrograms)-treated rats was associated with quantitative changes in the SS receptors. Equilibrium binding data obtained with [125I]Tyr11-SS indicate an increase in the number with specific SS receptors (541 +/- 24 vs. 365 +/- 16 fmol/mg protein, P histamine (10 micrograms)-treated rats as compared to control animals. With the aim of determining if these changes were related to histamine binding to its specific receptor sites, the histaminergic H1 and H2 receptor antagonists mepyramine and cimetidine, respectively, were administered 1 h before histamine injection. The pretreatment with mepyramine or cimetidine induced an increase in the

  9. Antidepressant-like effects of endogenous histamine and of two histamine H1 receptor agonists in the mouse forced swim test

    OpenAIRE

    Lamberti, Claudia; Ipponi, Alessandro; Bartolini, Alessandro; Schunack, Walter; Malmberg-Aiello, Petra

    1998-01-01

    Effects of substances which are able to alter brain histamine levels and two histamine H1 receptor agonists were investigated in mice by means of an animal model of depression, the forced swim test.Imipramine (10 and 30 mg kg−1, i.p.) and amitriptyline (5 and 15 mg kg−1, i.p.) were used as positive controls. Their effects were not affected by pretreatment with the histamine H3 receptor agonist, (R)-α-methylhistamine, at a dose (10 mg kg−1, i.p.) which did not modify the cumulative time of imm...

  10. Effects of histamine on spontaneous neuropathic pain induced by peripheral axotomy

    Institute of Scientific and Technical Information of China (English)

    Jie Yu; Guo-Dong Lou; Jia-Xing Yue; Ying-Ying Tang; Wei-Wei Hou; Wen-Ting Shou; Hiroshi Ohtsu

    2013-01-01

    The present study was designed to investigate the effects of histamine on spontaneous neuropathic pain (NP) induced by peripheral axotomy.Rats and mice were subjected to complete transection of the left sciatic and saphenous nerves to induce spontaneous NP (the neuroma model).Rats were then treated with drugs once daily for 30 days (histidine and Ioratadine,i.p.) or 21 days (histamine,i.c.v.).Autotomy behavior was scored daily until day 50 post-operation (PO).On days 14 to 21 PO,some rats in the control group were subjected to single-fiber recording.Autotomy behavior was also monitored daily in histidine decarboxylase (the key enzyme for histamine synthesis) knockout (HDC~) and wild-type mice for 42 days.We found that both histidine (500 mg/kg) (a precursor of histamine that increases histamine levels in the tissues) and histamine (50 μg/5 μL) significantly suppressed autotomy behavior in rats.HDC-/-mice lacking endogenous histamine showed higher levels of autotomy than the wild-type.In addition,the analgesic effect of histidine was not antagonized by Ioratadine (a peripherally-acting H1 receptor antagonist),while Ioratadine alone significantly suppressed autotomy.Electrophysiological recording showed that ectopic spontaneous discharges from the neuroma were blocked by systemic diphenhydramine (an H1 receptor antagonist).Our results suggest that histamine plays an important role in spontaneous NP.It is likely that histamine in the central nervous system is analgesic,while in the periphery,via H1 receptors,it is algesic.This study justifies the avoidance of a histamine-rich diet and the use of peripherally-acting H1 receptor antagonists as well as agents that improve histamine action in the central nervous system in patients with spontaneous NP.

  11. Spinal histamine in attenuation of mechanical hypersensitivity in the spinal nerve ligation-induced model of experimental neuropathy.

    Science.gov (United States)

    Wei, Hong; Viisanen, Hanna; You, Hao-Jun; Pertovaara, Antti

    2016-02-05

    Here we studied whether and through which mechanisms spinal administration of histamine dihydrochloride (histamine) attenuates pain behavior in neuropathic animals. Experiments were performed in rats with spinal nerve ligation-induced neuropathy and a chronic intrathecal catheter for spinal drug delivery. Mechanical hypersensitivity was assessed with monofilaments while radiant heat was used for assessing nociception. Ongoing neuropathic pain and its attenuation by histamine was assessed using conditioned place-preference test. Following spinal administration, histamine at doses 0.1-10µg produced a dose-related mechanical antihypersensitivity effect. With prolonged treatment (twice daily 10µg for five days), the antihypersensitivity effect of spinal histamine was reduced. In place-preference test, neuropathic animals preferred the chamber paired with histamine (10µg). Histamine (10µg) failed to influence heat nociception in neuropathic animals or mechanically induced pain behavior in a group of healthy control rats. Histamine-induced mechanical antihypersensitivity effect was prevented by spinal pretreatment with zolantidine (histamine H2 receptor antagonist), prazosine (α1-adrenoceptor antagonist) and bicuculline (γ-aminobutyric acid subtype A, GABA(A), receptor antagonist), but not by pyrilamine (histamine H1 receptor antagonist), atipamezole (α2-adrenoceptor antagonist), or raclopride (dopamine D2 receptor antagonist). A-960656, a histamine H3 receptor antagonist alone that presumably increased endogenous histamine levels reduced hypersensitivity. Additionally, histamine prevented central (presumably postsynaptically-induced) facilitation of hypersensitivity induced by N-methyl-d-aspartate. The results indicate that spinal histamine at the dose range of 0.1-10µg selectively attenuates mechanical hypersensitivity and ongoing pain in neuropathy. The spinal histamine-induced antihypersensitivity effect involves histamine H2 and GABA(A) receptors and

  12. Enhanced morphine-induced antinociception in histamine H3 receptor gene knockout mice.

    Science.gov (United States)

    Mobarakeh, Jalal Izadi; Takahashi, Kazuhiro; Yanai, Kazuhiko

    2009-09-01

    Previous studies have implicated a potential role for histamine H3 receptor in pain processing. There have been conflicting data, however, on the roles of H3 receptors in pain perception, and little information is available about the role of spinal histamine H3 receptors in morphine-induced antinociception. In the present study we examined the role of histamine H3 receptor in morphine-induced antinociception using histamine H3 receptor knockout mice and a histamine H3 receptor antagonist. Anitinociception was evaluated by assays for four nociceptive stimuli: hot-plate, tail-flick, paw-withdrawal, and formalin tests. Antinociception induced by morphine (0.125 nmol/5 microl, i.t.) was significantly augmented in histamine H3 receptor knockout (-/-) mice compared to the wild-type (+/+) mice in all four assays of pain. Furthermore, the effect of intrathecally administered morphine with thioperamide, a histamine H3 antagonist, was examined in C57BL/6J mice. A low dose of i.t. administered thioperamide (0.125 nmol/5 microl) alone had no significant effect on the nociceptive response. In contrast, the combination of morphine (0.125 nmol/5 microl, i.t.) with the same dose of thioperamide resulted in a significant reduction in the pain-related behaviors in all four nociceptive tests. These results suggest that histamine exerts inhibitory effects on morphine-induced antinociception through H3 receptors at the spinal level.

  13. Histamine-producing pathway encoded on an unstable plasmid in Lactobacillus hilgardii 0006

    NARCIS (Netherlands)

    Lucas, PM; Wolken, WAM; Claisse, O; Lolkema, JS; Lonvaud-Funel, A; Lucas, Patrick M.; Wolken, Wout A.M.

    2005-01-01

    Histamine production from histidine in fermented food products by lactic acid bacteria results in food spoilage and is harmful to consumers. We have isolated a histamine-producing lactic acid bacterium, Lactobacillus hilgardii strain IOEB 0006, which could retain or lose the ability to produce hista

  14. Biphasic changes in body temperature produced by intracerebroventricular injections of histamine in the cat.

    Science.gov (United States)

    Clark, W G; Cumby, H R

    1976-09-01

    1. Intracerebroventricular administration of histamine to cats caused hypothermia followed by a rise in body temperature. 2-Methylhistamine caused a similar biphasic response, while 3-methylhistamine had no effect on body temperature and 4-methylhistamine produced a delayed hyperthermia. Some tolerance to the hypothermic activity developed when a series of closely spaced injections of histamine was given. 2. Doses of histamine and 2-methylhistamine which altered body temperature when given centrally were ineffective when infused or injected I.V. 3. Pyrilamine, an H1-receptor antagonist, prevented the hypothermic response to histamine. 4. Hypothermic responses to histamine at an environmental temperature of 22 degrees C were comparable to responses in a cold room at 4 degrees C in both resting animals and animals acting to depress a lever to escape an external heat load. A change in error signal from the thermostat could account for these results. However, lesser degrees of hypothermia developed when histamine was given to animals in a hot environment. In some, but not all animals, this smaller response could be attributed to inadequate heat loss in spite of maximal activation of heat-loss mechanisms. 5. The hyperthermic response to histamine was antagonized by central, but not peripheral, injection of metiamide, an H2-receptor antagonist. 6. The results indicate that histamine and related agents can act centrally to cause both hypothermia, mediated by H1-receptors, and hyperthermia, mediated by H2-receptors.

  15. Effects of histamine and opioid systems on memory retention of passive avoidance learning in rats.

    Science.gov (United States)

    Zarrindast, Mohammad-Reza; Eidi, Maryam; Eidi, Akram; Oryan, Shahrbano

    2002-10-04

    The present study investigated the effect of interactions between histamine receptor agents and the opioid peptidergic system on memory retention of passive avoidance learning in rats. Post-training intracerebroventricular (i.c.v.) injections were carried out in all the experiments. Administration of histamine (20 micro g/rat) reduced, but the histamine H(1) receptor antagonist, pyrilamine (20 and 50 micro g/rat), and the histamine H(2) receptor antagonist, cimetidine (10 and 50 micro g/rat), increased memory retention in rats. The histamine receptor antagonists decreased the response induced by histamine. Morphine (1-10 micro g/rat) reduced, while pentazocine (5 and 10 micro g/rat) or the opioid receptor antagonist, naloxone (5 and 15 micro g/rat), increased memory retention. The combination of histamine with morphine showed potentiation. Effects of pyrilamine and cimetidine were attenuated by morphine. The responses to pentazocine and naloxone also were decreased by histamine. It is concluded that the histaminergic system has an interaction with opioidergic system that is involved in the memory retention process.

  16. Evidence for an inhibitory role of central histamine on carrageenin-induced hyperalgesia.

    Science.gov (United States)

    Netti, C; Sibilia, V; Guidobono, F; Villani, P; Pecile, A; Braga, P C

    1994-02-01

    The effects of intracerebroventricular (i.c.v.) injection of histamine, the H1 agonist 2-methyl-histamine and the H2 agonist dimaprit were tested on carrageenin induced hyperalgesia by the Randall-Selitto paw pressure test in the rat. Treatment with histamine (0.1, 0.2, 0.4 mumol/rat, i.c.v.) 150 min after intraplantar carrageenin (0.1 ml of 1% solution) caused a significant increase of paw pressure thresholds in inflamed (but not in non-inflamed) paws. The magnitude and the duration of the antinociceptive effects of histamine were dose-dependent. Administration of 2-methyl-histamine (0.2, 0.4, 0.8, 1.0 mumol/rat, i.c.v.) and dimaprit (0.1, 0.2, 0.4, 0.8 mumol/rat, i.c.v.) also displayed dose-dependent blockade of carrageenin-induced hyperalgesia. Antinociceptive ED50 values calculated 30 min after drug treatments were: histamine 0.18 mumol/rat; 2-methyl-histamine 0.65 mumol/rat; dimaprit 0.33 mumol/rat. These data indicate that histamine through central H1 and H2 receptors exerts an inhibitory role in the control of nociception in pain resulting from inflammation.

  17. Histamine induces postprandian tachycardia through a direct effect on cardiac H2-receptors in pythons

    DEFF Research Database (Denmark)

    Jensen, Nini Skovgaard; Møller, Kate; Gesser, Hans

    2009-01-01

    snakes histamine caused a systemic vasodilatation and a marked increase in heart rate and cardiac output mediated through a direct effect on H2-receptors. Our study strongly indicates that histamine regulates heart rate during the initial phase of digestion in pythons. This study describes a novel...

  18. Effects of histamine on growth and apoptosis of human melanoma cells A375

    Institute of Scientific and Technical Information of China (English)

    RAN Li-wei; TAN Sheng-shun; XU Xin-ling; ZHANG Jiang-an; WANG Wan-juan

    2005-01-01

    Objective: To investigate the effects of histamine on growth and apoptosis of human melanoma cells A375. Methods: The effect of histamine on growth of A375 cells in vitro was examined by MTT assay and Trypan blue exclusion assay. Cell cycle analysis, early apoptosis analysis by double staining with Annexin V-FITC and PI, and active caspase-3 analysis by staining FITC-conjugated monoclonal rabbit anti-active caspase-3 antibody were made by flow cytometer. StreptAvidin-Biotin Complex (SABC)immunocytochemical assays were adopted to detect Bax/Bcl-2 protein expressions. Results: Histamine inhibited proliferation of A375 cells in a dose- and time-dependent manner, and altered cell cycle distribution of A375 cells revealing an increase in G0/G1-phase population, a decrease in S-phase population and the inhibition of G1/S switching. Histamine induced apoptosis of A375 cells (P<0. 05), elevated the cells population with detectable active caspase-3 (P<0. 05), increased the number of cells forming Bax and decreased the number of cells forming Bcl-2 significantly (P<0.05). Conclusion: That histamine inhibits cell cycle progress of A375 cells is one of the possible mechanisms of proliferation arrest of A375 cells elicited by histamine. Histamine mediates apoptosis in A375 cells that may be caspase-dependent through mitochondria routine. Histamine with high concentration inhibits growth of A375 cells in vitro by interfering proliferation and inducing apoptosis of cells.

  19. Comparison of nasal responsiveness to histamine, methacholine and phentolamine in allergic rhinitis patients and controls

    NARCIS (Netherlands)

    R. Gerth van Wijk (Roy); P.H. Dieges

    1987-01-01

    textabstractIn a selected group of rhinitis patients with an IgE‐mediated allergy to house dust mites the nasal response to insufflation of histamine chloride, methacholine and phentolamine was demonstrated to be higher than in a control group. With the methods used histamine chloride was better at

  20. Determination of histamine in fish by Surface Enhanced Raman Spectroscopy using silver colloid SERS substrates.

    Science.gov (United States)

    Janči, Tibor; Valinger, Davor; Gajdoš Kljusurić, Jasenka; Mikac, Lara; Vidaček, Sanja; Ivanda, Mile

    2017-06-01

    This study was focused on development of a rapid and sensitive method for histamine determination in fish based on Surface Enhanced Raman Spectroscopy (SERS) using simple and widely available silver colloid SERS substrate. Extraction of histamine with 0.4M perchloric acid and purification with 1-butanol significantly shortened sample preparation (30min) and provided clear SERS spectra with characteristic Raman bands of histamine. Principal component analysis effectively distinguished SERS spectra of fish samples with different histamine content. Partial least square (PLS) regression models confirmed reliability of detection and spectral analysis of histamine with SERS. In histamine concentration range 0-200mgkg(-1), significant in legislative and fish quality control aspects, PLS regression model based on spectral range 1139.9-1643.7cm(-1) showed linear trend with R(2)pred=0.962, RPD=7.250. Presented protocol for histamine extraction and purification followed by SERS analysis coupled with chemometric approach, enabled development of rapid and inexpensive method for histamine determination in fish.

  1. Enhancement of ionizing radiation response by histamine in vitro and in vivo in human breast cancer.

    Science.gov (United States)

    Martinel Lamas, Diego J; Cortina, Jorge E; Ventura, Clara; Sterle, Helena A; Valli, Eduardo; Balestrasse, Karina B; Blanco, Horacio; Cremaschi, Graciela A; Rivera, Elena S; Medina, Vanina A

    2015-01-01

    The radioprotective potential of histamine on healthy tissue has been previously demonstrated. The aims of this work were to investigate the combinatorial effect of histamine or its receptor ligands and gamma radiation in vitro on the radiobiological response of 2 breast cancer cell lines (MDA-MB-231 and MCF-7), to explore the potential molecular mechanisms of the radiosensitizing action and to evaluate the histamine-induced radiosensitization in vivo in a triple negative breast cancer model. Results indicate that histamine significantly increased the radiosensitivity of MDA-MB-231 and MCF-7 cells. This effect was mimicked by the H1R agonist 2-(3-(trifluoromethyl)phenyl)histamine and the H4R agonists (Clobenpropit and VUF8430) in MDA-MB-231 and MCF-7 cells, respectively. Histamine and its agonists enhanced radiation-induced oxidative DNA damage, DNA double-strand breaks, apoptosis and senescence. These effects were associated with increased production of reactive oxygen species, which correlated with the inhibition of catalase, glutathione peroxidase and superoxide dismutase activities in MDA-MB-231 cells. Histamine was able also to potentiate in vivo the anti-tumoral effect of radiation, increasing the exponential tumor doubling time. We conclude that histamine increased radiation response of breast cancer cells, suggesting that it could be used as a potential adjuvant to enhance the efficacy of radiotherapy.

  2. Comparable profiles of serum histamine and IgG4 levels in allergic beekeepers.

    Science.gov (United States)

    Chliva, C; Aggelides, X; Makris, M; Katoulis, A; Rigopoulos, D; Tiligada, E

    2015-04-01

    Growing evidence identifies histamine as a key player in allergic responses, but the reports relating serum histamine to tolerance are scarce and inconclusive. This study investigated the relationship of circulating histamine to the tolerant phenotype in allergic beekeepers. The results showed a positive correlation between the serum levels of histamine and specific immunoglobulin G4 (sIgG4) to honeybee venom, but not with total IgE or sIgE. Interestingly, both sIgG4 and histamine levels were negatively correlated with the time since the last bee sting. In contrast to total IgE and sIgE, serum sIgG4 and histamine levels followed comparable patterns, being higher in tolerant/recently stung individuals and lower in the least frequently stung subgroup. The data obtained in this pilot study associated, for the first time, serum histamine levels with allergen tolerance in allergic individuals and provided the lead for further considering the putative immunomodulatory properties of histamine in allergic responses.

  3. Interaction Between Brain Histamine and Serotonin, Norepinephrine, and Dopamine Systems: In Vivo Microdialysis and Electrophysiology Study.

    Science.gov (United States)

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

    2015-06-01

    Brain monoamines (serotonin, norepinephrine, dopamine, and histamine) play an important role in emotions, cognition, and pathophysiology and treatment of mental disorders. The interactions between serotonin, norepinephrine, and dopamine were studied in numerous works; however, histamine system received less attention. The aim of this study was to investigate the interactions between histamine and other monoamines, using in vivo microdialysis and electrophysiology. It was found that the inverse agonist of histamine-3 receptors, thioperamide, increased the firing activity of dopamine neurons in the ventral tegmental area. Selective agonist of histamine-3 receptors, immepip, reversed thiperamide-induced stimulation of firing activity of dopamine neurons. The firing rates of serotonin and norpeinephrine neurons were not attenuated by immepip or thioperamide. Thioperamide robustly and significantly increased extracellular concentrations of serotonin, norepinephrine, and dopamine in the rat prefrontal cortex and slightly increased norepinephrine and dopamine levels in the tuberomammillary nucleus of the hypothalamus. It can be concluded that histamine stimulates serotonin, norepinephrine, and dopamine transmission in the brain. Modulation of firing of dopamine neurons is a key element in functional interactions between histamine and other monoamines. Antagonists of histamine-3 receptors, because of their potential ability to stimulate monoamine neurotransmission, might be beneficial in the treatment of mental disorders.

  4. Role of histidine/histamine in carnosine-induced neuroprotection during ischemic brain damage.

    Science.gov (United States)

    Bae, Ok-Nam; Majid, Arshad

    2013-08-21

    Urgent need exists for new therapeutic options in ischemic stroke. We recently demonstrated that carnosine, an endogenous dipeptide consisting of alanine and histidine, is robustly neuroprotective in ischemic brain injury and has a wide clinically relevant therapeutic time window. The precise mechanistic pathways that mediate this neuroprotective effect are not known. Following in vivo administration, carnosine is hydrolyzed into histidine, a precursor of histamine. It has been hypothesized that carnosine may exert its neuroprotective activities through the histidine/histamine pathway. Herein, we investigated whether the neuroprotective effect of carnosine is mediated by the histidine/histamine pathway using in vitro primary astrocytes and cortical neurons, and an in vivo rat model of ischemic stroke. In primary astrocytes, carnosine significantly reduced ischemic cell death after oxygen-glucose deprivation, and this effect was abolished by histamine receptor type I antagonist. However, histidine or histamine did not exhibit a protective effect on ischemic astrocytic cell death. In primary neuronal cultures, carnosine was found to be neuroprotective but histamine receptor antagonists had no effect on the extent of neuroprotection. The in vivo effect of histidine and carnosine was compared using a rat model of ischemic stroke; only carnosine exhibited neuroprotection. Taken together, our data demonstrate that although the protective effects of carnosine may be partially mediated by activity at the histamine type 1 receptor on astrocytes, the histidine/histamine pathway does not appear to play a critical role in carnosine induced neuroprotection.

  5. Cardiovascular effects of histamine administered intracerebroventricularly in critical haemorrhagic hypotension in rats.

    Science.gov (United States)

    Jochem, J

    2000-06-01

    The study was designed to determine the cardiovascular effects of histamine administered intracerebroventricularly (icv) in a rat model of volume-controlled haemorrhagic shock. The withdrawal of approximately 50% of total blood volume resulted in the death of all control saline icv treated animals within 30 min. Icv injection of histamine produced a prompt dose-dependent (0.1-100 nmol) and long-lasting (10-100 nmol) increase in mean arterial pressure (MAP), pulse pressure (PP) and heart rate (HR), with a 100% survival of 2h after treatment (100 nmol). The increase in MAP and HR after histamine administration in bled rats in comparison to the normovolaemic animals was 2.7-3.3- and 1.3-3.6-fold higher, respectively. Pretreatment with chlorpheniramine (50 nmol icv), H1 receptor antagonist, inhibited the increase in MAP, PP, HR and survival rate produced by histamine, while chlorpheniramine given alone had no effect. Neither ranitidine (50 nmol icv), H2 histamine receptor antagonist, nor thioperamide (50 nmol icv), H3 receptor blocker, influenced the histamine action, however, when given alone, both evoked the pressor effect with elongation of survival time. It can be concluded that histamine administered icv reverses the haemorrhagic shock conditions, and histamine H1 receptors are involved.

  6. Histamine H3 recetpor antagonists: research advances%组胺H3受体拮抗剂的研究进展

    Institute of Scientific and Technical Information of China (English)

    王欢; 郑志兵; 李松

    2012-01-01

    组胺H3受体是G蛋白偶联受体超家族成员之一,调节组胺及其他多种神经递质的合成与释放.以组胺H3受体为靶点设计开发的组胺H3受体拮抗剂对于临床治疗阿尔茨海默病、帕金森病、嗜睡症等中枢社经系统疾病具有一定应用前景.组胺H3受体拮抗剂已成为当今抗组胺药物研究的一个热点领域,并已成功研制出大量高效、高选择性H3受体拮抗剂,部分化合物已进入临床研究.本文对近年来H3受体拮抗剂的研究进展进行综述.%Histamine H3 receptor, a member of G-protein-coupled receptor family, regulates the synthesis and release of hista-mine and various major neurotransmitters. As a novel therapeutic target for Alzheimer's disease, Parkinson's disease and narcolepsy, Histamine H3 receptor has a certain prospect. Hence, more and more institutions focus on the research and develponent of H3 receptor antagonists. Many highly selective and potent H3 receptor antagonists have been developed, some of which have advanced to clinical trials. This thesis reviews the development of histamine H3 receptor antagonists in recent years.

  7. Inhibition of in vivo histamine metabolism in rats by foodborne and pharmacologic inhibitors of diamine oxidase, histamine N-methyltransferase, and monoamine oxidase

    Energy Technology Data Exchange (ETDEWEB)

    Hui, J.Y.; Taylor, S.L.

    1985-11-01

    When (/sup 14/C)histamine was administered orally to rats, an average of 80% of the administered radioactivity was recovered in the urine at the end of 24 hr. About 10% of the total dose was excreted via the feces. Analysis of 4-hr urine samples found imidazoleacetic acid to be the predominant metabolite (60.6%), with N tau-methylimidazoleacetic acid (8.6%), N tau-methylhistamine (7.3%), and N-acetylhistamine (4.5%) to be the minor metabolites. Histamine metabolism was inhibited by simultaneous oral administration of aminoguanidine, isoniazid, quinacrine, cadaverine, putrescine, tyramine, and beta-phenylethylamine. The administration of inhibitors resulted in an increased amount of unmetabolized histamine and a decreased amount of metabolites reaching the urine. Pharmacologic inhibitors were found to be more potent and have a longer duration of action than foodborne ones. The inhibitors could potentiate food poisoning caused by histamine by inhibiting its metabolism.

  8. Antinociception induced by central administration of histamine in the formalin test in rats.

    Science.gov (United States)

    Mojtahedin, Ali; Tamaddonfard, Esmaeal; Zanboori, Ali

    2008-01-01

    In the present study, effects of intracerebroventricular (icv) administration of histamine, mepyramine (H1-receptor antagonist) and famotidine (H2-receptor antagonist) have been investigated on the formalin test in rats. Subcutaneous injection of formalin (50 microl, 1%) into the ventral surface of the left hind paw produced a marked biphasic pain response (first phase: 0-5 min and second phase: 15-45 min). All the performed treatments did not significantly influence the first phase of pain. Histamine at the doses of 10 and 40 microg and mepyramine and famotidine at the same doses of 20 and 80 microg, significantly (P histamine (40 microg)-induced antinociception. These results indicate that brain histamine produces antinociception, and both central H1 and H2 receptors may involve in the histamine-induced antinociception in the formalin test in rats.

  9. Central effect of histamine in a rat model of acute trigeminal pain.

    Science.gov (United States)

    Tamaddonfard, Esmaeal; Khalilzadeh, Emad; Hamzeh-Gooshchi, Nasrin; Seiednejhad-Yamchi, Sona

    2008-01-01

    In conscious rats implanted with an intracerebroventricular (icv) cannula, effect of icv injections of histamine, chlorpheniramine (H(1)-receptor antagonist) and ranitidine (H(2)-receptor blocker) was investigated in a rat model of acute trigeminal pain. Acute trigeminal pain was induced by putting a drop of 5 M NaCl solution on the corneal surface of the eye and the numbers of eye wipes were counted during the first 30 s. Histamine (20, 40 microg) and chlorpheniramine (80 microg) significantly decreased the numbers of eye wipes. Ranitidine alone had no effect. Pretreatment with chlorpheniramine did not change the histamine-induced analgesia, whereas the histamine effect on pain was inhibited with ranitidine pretreatment. These results indicate that the brain histamine, through central H(2) receptors, may be involved in the modulation of the acute trigeminal pain in rats.

  10. Effects of intracerebroventricular injection of histamine and its related compounds on rectal temperature in mice.

    Science.gov (United States)

    Chen, Z; Sugimoto, Y; Kamei, C

    1995-12-01

    Effects of intracerebroventricular injection of histamine and its related compounds on rectal temperature were studied in mice. Histamine (0.1-1.0 mu g) and histidine (500-1,000 mg/kg) caused a dose-related hypothermia. H1 agonist, 2-methylhistamine and 2-thiazolylethylamine also displayed a dose-dependent hypothermia. In addition, H2 agonists, 4-methylhistamine and dimaprit elicited a decrease in body temperature. Preinjection of not only H1-antagonists (diphenhydramine and chlorpheniramine) but also H2 antagonists (cimetidine and ranitidine) abolished histamine-induced hypothermia. Either intracerebroventricular or intraperitoneal injection of thioperamide, a histamine H3 antagonist, showed hypothermia. The hypothermic effect produced by intracerebroventricular injection of thioperamide was significantly blocked by (R)-alpha-methylhistamine, a selective H3 agonist. In addition, the effect induced by thioperamide was inhibited by H1 and H2 antagonists, indicating that the H3 receptor also participates in histamine-induced hypothermia.

  11. Leukotriene C4 and histamine in early allergic reaction in the nose

    DEFF Research Database (Denmark)

    Bisgaard, H; Robinson, C; Rømeling, F

    1988-01-01

    We have examined the measurements of LTC4 and histamine in nasal lavage fluids and blown secretions as a possible model of the early mediator events during nasal allergy. A nasal challenge with grass pollen extract was undertaken on two separate occasions in 20 patients with a history of seasonal......mTc-labelled albumin as an exogenous marker added to the fluid. The amounts of admixture in the nasal lavages did not correlate to the concentrations of LTC4 and histamine, indicating that the variable amounts of nasal secretion in nasal lavage do not constitute a confounding variable...... for measurements of LTC4 and histamine. In the pre-challenge lavages, the median concentrations, of LTC4 and histamine were 1.7 and 52 nmol/l respectively. Following allergen challenge neither LTC4 nor histamine measured in nasal lavage showed any significant change from pre-challenge baseline values. However...

  12. 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

    We have previously proposed that histamine causes migraine via increased NO production. To test this hypothesis, we here examined if the NOS inhibitor, L-NG methylarginine hydrochloride (L-NMMA:546C88), could block or attenuate histamine induced migraine attacks and responses of the middle cerebral......, temporal and radial arteries. In a double blind crossover design 12 patients were randomized to receive pretreatment with L-NMMA (6 mg/kg) or placebo i.v. over 15 min followed on both study days by histamine (0.5 microg/kg/min) i.v. for 20 min. Headache scores, mean maximal blood velocity (Vmean......) in the middle cerebral artery (MCA) (transcranial doppler) and diameters of temporal and radial arteries (high resolution ultrasound) were repeatedly measured. Pre-treatment with L-NMMA, had no effect on histamine induced headache or migraine, but also had no effect on the magnitude of histamine induced...

  13. Disodium cromoglycate prevents ileum hyperreactivity to histamine in Toxocara canis-infected guinea pigs.

    Science.gov (United States)

    Sá-Nunes, A; Corrado, A P; Baruffi, M D; Faccioli, L H

    2003-11-01

    The aim of this study was to investigate whether Toxocara canis infection in guinea pigs provokes changes in ileum responsiveness to histamine. Ileum segments from control and T. canis-infected groups were placed at isometric conditions and submitted to various doses of histamine. No changes were observed between controls and T. canis-infected groups at days 3, 6 and 12 after infection. However, at days 18 and 24 after infection, there was a significant increase in ileum responsiveness to histamine in T. canis-infected group. Pre-incubation of ileum segments with 1mgml(-1) disodium cromoglycate (DSCG) prevented the increased responsiveness to histamine in T. canis-infected guinea pigs and did not affect ileum contractility in non-infected animals. These results indicate that T. canis-infected guinea pigs develop increased intestinal responsiveness to histamine and that DSCG prevents alterations in smooth-muscle contractility.

  14. 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.

  15. Virus and bacteria enhance histamine production in middle ear fluids of children with acute otitis media.

    Science.gov (United States)

    Chonmaitree, T; Patel, J A; Lett-Brown, M A; Uchida, T; Garofalo, R; Owen, M J; Howie, V M

    1994-06-01

    Histamine levels were measured in 677 middle ear fluid (MEF) samples from 248 children (aged 2 months to 7 years) with acute otitis media (AOM); of these, 116 (47%) had documented viral infection. Histamine content was higher in bacteria-positive than in bacteria-negative MEF samples (P = .007) and higher in samples from patients with viral infection than in those from patients with no viral infection (P = .002). Bacteria and viruses together had an additive effect on histamine content in MEF. Histamine concentration in the initial MEF sample tended to be higher in patients with persistent otitis than in those with good response to treatment (P = .14). Results suggest that viruses, bacteria, or both induce histamine production, which leads to increased inflammation in the middle ear. Antihistaminic drugs may be beneficial. Large, prospective, controlled trials of the effects of antihistamine as an adjunct therapy in bacterial and viral AOM are required before recommendations can be made.

  16. H3 receptor-mediated inhibition of noradrenaline release: an investigation into the involvement of Ca2+ and K+ ions, G protein and adenylate cyclase.

    Science.gov (United States)

    Schlicker, E; Kathmann, M; Detzner, M; Exner, H J; Göthert, M

    1994-07-01

    The present study was aimed at the identification of mechanisms following the activation of histamine H3 receptors. Mouse brain cortex slices preincubated with 3H-noradrenaline were superfused and the (H3 receptor-mediated) effect of histamine on the electrically evoked tritium overflow was studied under a variety of conditions. The extent of inhibition produced by histamine was inversely related to the frequency of stimulation used to evoke tritium overflow and to the Ca2+ concentration in the superfusion medium. An activator (levcromakalim) and blocker (glibenclamide) of ATP-dependent K+ channels did not affect the electrically evoked tritium overflow and its inhibition by histamine. A blocker of voltage-sensitive K+ channels, tetraethylammonium (TEA), increased the evoked overflow and attenuated the inhibitory effect of histamine. TEA also reduced the inhibitory effect of noradrenaline and prostaglandin E2 on the evoked overflow. When the facilitatory effect of TEA on the evoked overflow was compensated for by reducing the Ca2+ concentration in the superfusion medium, TEA did no longer attenuate the effect of histamine. Exposure of the slices to the SH group-alkylating agent N-ethylmaleimide increased the evoked overflow and attenuated the inhibitory effect of histamine; both effects were counteracted by the SH group-protecting agent dithiothreitol, which, by itself, did not affect the evoked overflow and its inhibition by histamine. Mouse brain cortex membranes were used to study the effect of the H3 receptor agonist R-(-)-alpha-methylhistamine on the basal cAMP accumulation and on the accumulation stimulated by forskolin or noradrenaline.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Mechanism of renal effects of intracerebroventricular histamine in rabbits.

    Science.gov (United States)

    Kook, Y J; Kim, K K; Yang, D K; Ahn, D S; Choi, B K

    1988-01-01

    Histamine, when given intracerebroventricularly (i.c.v.), has been reported to produce antidiuresis in the rabbit. In this study it was attempted to elucidate the mechanism involved in the effect. Histamine (H), 100 micrograms/kg i.c.v., produced antidiuresis with decreases in renal plasma flow and glomerular filtration rate in urethane-anesthetized rabbits. With larger doses, a tendency towards increased electrolyte excretion was noted in spite of decreased filtration. In the denervated kidney, marked diuresis and natriuresis were observed following i.c.v. H, whereas the contralateral innervated kidney responded with typical antidiuresis. Reserpinized rabbits also responded with marked natriuresis to i.c.v. H. Diphenhydramine (D), 250 micrograms/kg i.c.v., increased urine flow rate, sodium and potassium excretion, along with increase in renal perfusion. With 750 micrograms/kg i.c.v., marked natriuresis was observed in spite of decreased filtration. When H was given after D (250 micrograms/kg) the antidiuresis was completely abolished, and diuresis became more prominent. Cimetidine, 250 micrograms/kg i.c.v., elicited antidiuresis with decreases in renal hemodynamics, the pretreatment with cimetidine did not influence the antidiuresis by H and no natriuresis was noted. The present study suggests that histamine, given i.c.v., influences renal function in dual ways, i.e., antidiuresis by increasing the sympathetic tone to the kidney and diuresis due to some humoral natriuretic factor, the latter becoming apparent only when the former influence has been removed, and further suggests that H1-receptors might be involved in the nerve-mediated antidiuresis, whereas H2-receptors might mediate the humorally induced natriuresis and diuresis.

  18. Histamine Levels in Fish from Markets in Lima, Perú†

    Science.gov (United States)

    Gonzaga, Victor E.; Lescano, Andres G.; Huamán, Alfredo A.; Salmón-Mulanovich, Gabriela; Blazes, David L.

    2014-01-01

    Illnesses associated with seafood are an important public health concern worldwide, particularly considering the steady increase in seafood consumption. However, research about the risks associated with seafood products is scarce in developing countries. Histamine fish poisoning is the most common form of fish intoxication caused by seafood and usually presents as an allergic reaction. This condition occurs when fish are not kept appropriately refrigerated and histamine is formed in the tissues. Histamine levels of >500 ppm usually are associated with clinical illness. We assessed histamine levels in fish from markets in Lima, Peru, with a quantitative competitive enzyme-linked immunosorbent assay. Thirty-eight specimens were purchased from wholesale and retail markets: 17 bonito (Sarda sarda), 16 mackerel (Scomber japonicus peruanus), and 5 mahi-mahi (Coryphaena hippurus). Seven fish (18%) had histamine levels of 1 to 10 ppm (three mackerel and four bonito) and three (8%) had >10 ppm (three mackerel, 35 to 86 ppm). Fish from retail markets had detectable histamine levels (>1 ppm) more frequently than did fish bought at wholesale fish markets: 9 (36%) of 25 fish versus 1 (8%) of 13 fish, respectively (P = 0.063). Higher histamine levels were correlated with later time of purchase during the day (Spearman’s rho = 0.37, P = 0.024). Mackerel purchased at retail markets after 2 p.m. had a 75% prevalence of histamine levels of >10 ppm. Mackerel purchased late in the day in retail markets frequently contained high histamine levels, although the overall prevalence of elevated histamine levels was low. Despite the small sample, our findings highlight the need to reinforce seafood safety regulations and quality control in developing countries such as Peru. PMID:19517744

  19. Histamine levels in fish from markets in Lima, Perú.

    Science.gov (United States)

    Gonzaga, Victor E; Lescano, Andres G; Huamán, Alfredo A; Salmón-Mulanovich, Gabriela; Blazes, David L

    2009-05-01

    Illnesses associated with seafood are an important public health concern worldwide, particularly considering the steady increase in seafood consumption. However, research about the risks associated with seafood products is scarce in developing countries. Histamine fish poisoning is the most common form of fish intoxication caused by seafood and usually presents as an allergic reaction. This condition occurs when fish are not kept appropriately refrigerated and histamine is formed in the tissues. Histamine levels of > 500 ppm usually are associated with clinical illness. We assessed histamine levels in fish from markets in Lima, Peru, with a quantitative competitive enzyme-linked immunosorbent assay. Thirty-eight specimens were purchased from wholesale and retail markets: 17 bonito (Sarda sarda), 16 mackerel (Scomber japonicus peruanus), and 5 mahi-mahi (Coryphaena hippurus). Seven fish (18%) had histamine levels of 1 to 10 ppm (three mackerel and four bonito) and three (8%) had > 10 ppm (three mackerel, 35 to 86 ppm). Fish from retail markets had detectable histamine levels (> 1 ppm) more frequently than did fish bought at wholesale fish markets: 9 (36%) of 25 fish versus 1 (8%) of 13 fish, respectively (P = 0.063). Higher histamine levels were correlated with later time of purchase during the day (Spearman's rho = 0.37, P = 0.024). Mackerel purchased at retail markets after 2 p.m. had a 75% prevalence of histamine levels of > 10 ppm. Mackerel purchased late in the day in retail markets frequently contained high histamine levels, although the overall prevalence of elevated histamine levels was low. Despite the small sample, our findings highlight the need to reinforce seafood safety regulations and quality control in developing countries such as Peru.

  20. Ab initio calculation of the NMR shielding constants for histamine

    Science.gov (United States)

    Mazurek, A. P.; Dobrowolski, J. Cz.; Sadlej, J.

    1997-12-01

    The gage-independent atomic orbital (GIAO) approach is used within the coupled Hartree-Fock approximation to compute the 1H, 13C and 15N NMR shielding constants in two tautomeric forms of both the histamine molecule and its protonated form. An analysis of the results shows that the protonation on the end of the chain changes its nitrogen shielding constants of the pyridine and pyrrole type. These changes are much higher for the N(3)-H than for the N(1)-H tautomer.

  1. Interaktionen von Histamin H1-Rezeptoragonisten und –antagonisten mit dem humanen Histamin H4-Rezeptor

    OpenAIRE

    2012-01-01

    Der humane Histamin H(4)-Rezeptor (hH(4)R) zeichnet sich durch hohe konstitutive Aktivität aus und ist wie der humane H(1)-Rezeptor (hH(1)R) in die Pathogenese von allergischen Reaktionen vom Typ I involviert. Die Ziele der Untersuchungen waren die Evaluierung des Wertes von dualen H(1)/H(4)R Antagonisten als antiallergische Medikamente und die Klärung der Frage, ob H(1)R Liganden an den hH(4)R binden. Am in Sf9-Insektenzellen exprimierten hH(4)R zeigten 18 H(1)R Antagonisten und 22 H(1)R Ago...

  2. Diets high in heat-treated soybean meal reduce the histamine-induced epithelial response in the colon of weaned piglets and increase epithelial catabolism of histamine.

    Directory of Open Access Journals (Sweden)

    Susan Kröger

    Full Text Available We examined the influence of dietary fermentable protein (fCP and fermentable carbohydrates (fCHO on the colonic epithelial response to histamine in pigs. Thirty-two weaned piglets were fed 4 diets in a 2 × 2 factorial design with low fCP/low fCHO, low fCP/high fCHO, high fCP/low fCHO and high fCP/high fCHO. After 21-23 days, the pigs were killed and tissue from the proximal colon was stimulated with carbachol, histamine, PGE2 or sodium hydrogen sulphide in Ussing chambers. Changes in short-circuit current and tissue conductance were measured. Diamine oxidase, histamine N-methyltransferase, stem cell growth factor receptor, Fc-epsilon receptor I and cystic fibrosis transmembrane conductance regulator gene expression was determined. Activities of diamine oxidase and histamine N-methyltransferase and numbers of colonic mast cells were measured. The change in the short-circuit current in response to histamine was lower (P = 0.002 and tended to be lower for PGE2 (P = 0.053 in high fCP groups compared to low fCP groups, irrespective of fCHO. Additionally, the change in tissue conductance after the application of histamine was lower (P = 0.005 in the high fCP groups. The expression of histamine N-methyltransferase mRNA (P = 0.033 and the activities of diamine oxidase (P = 0.001 and histamine N-methyltransferase (P = 0.006 were higher with high fCP in comparison with low fCP. The expression of mast cell markers, stem cell growth factor receptor (P = 0.005 and Fc-epsilon receptor I (P = 0.049 was higher with high fCP diets compared to diets low in fCP, whereas the mast cell count did not differ between groups. The expression of the cystic fibrosis transmembrane conductance regulator was reduced (P = 0.001 with high fCP diets compared to low fCP diets. The lower epithelial response to histamine and PGE2 and elevated epithelial histamine inactivation suggests an adaptation to high fCP diets.

  3. Diets high in heat-treated soybean meal reduce the histamine-induced epithelial response in the colon of weaned piglets and increase epithelial catabolism of histamine.

    Science.gov (United States)

    Kröger, Susan; Pieper, Robert; Schwelberger, Hubert G; Wang, Jing; Villodre Tudela, Carmen; Aschenbach, Jörg R; Van Kessel, Andrew G; Zentek, Jürgen

    2013-01-01

    We examined the influence of dietary fermentable protein (fCP) and fermentable carbohydrates (fCHO) on the colonic epithelial response to histamine in pigs. Thirty-two weaned piglets were fed 4 diets in a 2 × 2 factorial design with low fCP/low fCHO, low fCP/high fCHO, high fCP/low fCHO and high fCP/high fCHO. After 21-23 days, the pigs were killed and tissue from the proximal colon was stimulated with carbachol, histamine, PGE2 or sodium hydrogen sulphide in Ussing chambers. Changes in short-circuit current and tissue conductance were measured. Diamine oxidase, histamine N-methyltransferase, stem cell growth factor receptor, Fc-epsilon receptor I and cystic fibrosis transmembrane conductance regulator gene expression was determined. Activities of diamine oxidase and histamine N-methyltransferase and numbers of colonic mast cells were measured. The change in the short-circuit current in response to histamine was lower (P = 0.002) and tended to be lower for PGE2 (P = 0.053) in high fCP groups compared to low fCP groups, irrespective of fCHO. Additionally, the change in tissue conductance after the application of histamine was lower (P = 0.005) in the high fCP groups. The expression of histamine N-methyltransferase mRNA (P = 0.033) and the activities of diamine oxidase (P = 0.001) and histamine N-methyltransferase (P = 0.006) were higher with high fCP in comparison with low fCP. The expression of mast cell markers, stem cell growth factor receptor (P = 0.005) and Fc-epsilon receptor I (P = 0.049) was higher with high fCP diets compared to diets low in fCP, whereas the mast cell count did not differ between groups. The expression of the cystic fibrosis transmembrane conductance regulator was reduced (P = 0.001) with high fCP diets compared to low fCP diets. The lower epithelial response to histamine and PGE2 and elevated epithelial histamine inactivation suggests an adaptation to high fCP diets.

  4. Histamine H1 antagonists and clinical characteristics of febrile seizures

    Directory of Open Access Journals (Sweden)

    Zolaly MA

    2012-03-01

    Full Text Available Mohammed A ZolalyDepartment of Pediatrics, College of Medicine, Taibah University, Al-Madinah Al-Munawarah, Kingdom of Saudi ArabiaBackground: The purpose of this study was to determine whether seizure susceptibility due to antihistamines is provoked in patients with febrile seizures.Methods: The current descriptive study was carried out from April 2009 to February 2011 in 250 infants and children who visited the Madinah Maternity and Children's Hospital as a result of febrile convulsions. They were divided into two groups according to administration of antihistamines at the onset of fever.Results: Detailed clinical manifestations were compared between patients with and without administration of antihistamines. The time from fever detection to seizure onset was significantly shorter in the antihistamine group than that in the nonantihistamine group, and the duration of seizures was significantly longer in the antihistamine group than in the nonantihistamine group. No significant difference was found in time from fever detection to seizure onset or seizure duration between patients who received a first-generation antihistamine and those who received a second-generation antihistamine.Conclusion: Due to their central nervous system effects, H1 antagonists should not be administered to patients with febrile seizures and epilepsy. Caution should be exercised regarding the use of histamine H1 antagonists in young infants, because these drugs could potentially disturb the anticonvulsive central histaminergic system.Keywords: antihistamine, nonantihistamine, histamine H1 antagonist, febrile seizures

  5. 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 H3 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. H3 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 D2, D3 and serotonin 5-HT1A receptors, antagonism at D2, 5-HT2A, 5-HT2B and 5-HT7 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 H3 antagonists/inverse agonists increase extracellular dopamine concentrations in rat prefrontal cortex, but not in the striatum suggesting that antagonism via H3 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 H3 receptors as a target of antiobesity therapeutics which

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

    Science.gov (United States)

    Mahmood, Danish

    2016-01-01

    Histamine H3 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. H3 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 D2, D3 and serotonin 5-HT1A receptors, antagonism at D2, 5-HT2A, 5-HT2B and 5-HT7 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 H3 antagonists/inverse agonists increase extracellular dopamine concentrations in rat prefrontal cortex, but not in the striatum suggesting that antagonism via H3 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 H3 receptors as a target of antiobesity therapeutics which

  7. Histamine H1 Receptor Gene Expression and Drug Action of Antihistamines.

    Science.gov (United States)

    Fukui, Hiroyuki; Mizuguchi, Hiroyuki; Nemoto, Hisao; Kitamura, Yoshiaki; Kashiwada, Yoshiki; Takeda, Noriaki

    2016-11-25

    The upregulation mechanism of histamine H1 receptor through the activation of protein kinase C-δ (PKCδ) and the receptor gene expression was discovered. Levels of histamine H1 receptor mRNA and IL-4 mRNA in nasal mucosa were elevated by the provocation of nasal hypersensitivity model rats. Pretreatment with antihistamines suppressed the elevation of mRNA levels. Scores of nasal symptoms were correlatively alleviated to the suppression level of mRNAs above. A correlation between scores of nasal symptoms and levels of histamine H1 receptor mRNA in the nasal mucosa was observed in patients with pollinosis. Both scores of nasal symptoms and the level of histamine H1 receptor mRNA were improved by prophylactic treatment of antihistamines. Similar to the antihistamines, pretreatment with antiallergic natural medicines showed alleviation of nasal symptoms with correlative suppression of gene expression in nasal hypersensitivity model rats through the suppression of PKCδ. Similar effects of antihistamines and antiallergic natural medicines support that histamine H1 receptor-mediated activation of histamine H1 receptor gene expression is an important signaling pathway for the symptoms of allergic diseases. Antihistamines with inverse agonist activity showed the suppression of constitutive histamine H1 receptor gene expression, suggesting the advantage of therapeutic effect.

  8. Histamine and spontaneous motor activity: biphasic changes, receptors involved and participation of the striatal dopamine system.

    Science.gov (United States)

    Chiavegatto, S; Nasello, A G; Bernardi, M M

    1998-01-01

    The time- and dose-related effects of exogenous histamine on spontaneous motor activity and receptors involved were evaluated in male rats. Intracerebroventricular administration of histamine (5.4 and 54.3 nmol) produced a biphasic effect with initial transitory hypoactivity and later hyperactivity expressed by locomotion frequency in an open-field. The rearing frequencies were only reduced by all doses of histamine used. The histamine-induced hypoactivity was inhibited by the H3-antagonist thioperamide and was also induced by the H3-agonist N-alpha-methylhistamine. The histamine-induced hyperactivity phase was blocked by the H1-antagonist mepyramine. The H2-antagonist ranitidine increased locomotion and rearing frequencies. The participation of other neurotransmitters in the persistent hypokinetic effect induced by 135.8 nmol of histamine was determined by HPLC in the striatum and hypothalamus as counter-proof. A decreased DOPAC/DA ratio was observed only in the striatum. In the hypothalamus, low levels of 5HT were detected, probably not correlated with motor activity. In conclusion, the present results suggest that the exogenous histamine-induced hypoactivity response is probably due to activation of H3-receptors as heteroreceptors reducing the activity of the striatal dopaminergic system. This effect can partially overlap with the expression of the hyperactivity induced by H1-receptor activation. The participation of H2-receptors requires further investigation.

  9. Effect of morphine, naloxone and histamine system on water intake in adult male rats.

    Science.gov (United States)

    Eidi, Maryam; Oryan, Shahrbanoo; Eidi, Akram; Sepehrara, Leili

    2003-10-08

    The present study investigated the interaction between histamine and opioid systems on water intake in adult male rats. Intracerebroventricular (i.c.v.) injections were carried out in all experiments. Water intake was measured 1 h after drug injections. Administration of histamine (40-80 microg/rat) and naloxone (0.5-1 microg/rat) increased, while morphine (2.5 microg/rat), pyrilamine (25-50 microg/rat), the histamine H1 receptor antagonist, and ranitidine (10-20 microg/rat), the histamine H2 receptor antagonist, decreased water intake in isolated rats. Blockade of histamine H1 and H2 receptors attenuated the histamine-induced response. Pyrilamine, but not ranitidine, increased the inhibitory effect induced by morphine. Also, pharmacological blockade of histamine H1 and H2 receptors decreased the naloxone-induced effect on water intake. It is concluded that the histaminergic system may have a close interaction with morphine and naloxone on drinking behavior.

  10. Effects of intracerebroventricular injection of histamine on memory deficits induced by hippocampal lesions in rats.

    Science.gov (United States)

    Kamei, C; Chen, Z; Nakamura, S; Sugimoto, Y

    1997-05-01

    The influence of bilateral hippocampal lesions on active avoidance response was studied in rats, as well as the effect of intracerebroventricular (i.c.v.) injection of histamine on memory deficits caused by hippocampectomy. Retardation of learning acquisition was produced by lesioning of the bilateral dorsal hippocampus in active avoidance response. Memory retention was also impaired by hippocampectomy. Although locomotor activity and rearing behavior measured by open-field test increased after hippocampal lesions, there was no relation between impairment of learning and increase in exploratory behavior. I.c.v. injection of histamine and i.p. injection of histidine resulted in an improvement of memory deficits (not only learning acquisition but also memory retrieval) induced by hippocampal lesions in rats. Histamine contents of the hippocampus and hypothalamus decreased after hippocampectomy, and a decrease in histamine contents of both areas was restored by histamine (i.c.v.) and histidine (i.p.) injection. In addition, a close relationship was found between decrease in response latency of avoidance response and an increase in histamine content of the hippocampus and hypothalamus after histamine injection.

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

    Energy Technology Data Exchange (ETDEWEB)

    Ruiz-Chica, A.J. [Departamento de Quimica Fisica, Facultad de Ciencias, Universidad de Malaga, 29071 Malaga (Spain); Soriano, A. [Departamento de Quimica Fisica/IcMol, Facultad de Quimicas, Universidad de Valencia, 46100 Burjassot Valencia (Spain); Tunon, I. [Departamento de Quimica Fisica/IcMol, Facultad de Quimicas, Universidad de Valencia, 46100 Burjassot Valencia (Spain); Sanchez-Jimenez, F.M. [Departamento de Bioquimica y Biologia Molecular, Facultad de Ciencias, Universidad de Malaga, 29071 Malaga (Spain); Silla, E. [Departamento de Quimica Fisica/IcMol, Facultad de Quimicas, Universidad de Valencia, 46100 Burjassot Valencia (Spain); Ramirez, F.J. [Departamento de Quimica Fisica, Facultad de Ciencias, Universidad de Malaga, 29071 Malaga (Spain)], E-mail: ramirez@uma.es

    2006-05-31

    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.

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

    Science.gov (United States)

    Ruiz-Chica, A. J.; Soriano, A.; Tuñón, I.; Sánchez-Jiménez, F. M.; Silla, E.; Ramírez, F. J.

    2006-05-01

    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.

  13. Histamine suppresses regulatory T cells mediated by TGF-β in murine chronic allergic contact dermatitis.

    Science.gov (United States)

    Tamaka, Kyoko; Seike, Masahiro; Hagiwara, Tamio; Sato, Atsushi; Ohtsu, Hiroshi

    2015-04-01

    Regulatory T cells (Tregs) suppress effector T cells and ameliorate contact hypersensitivity (CH); however, the role of Tregs in chronic allergic contact dermatitis (CACD) has not been assessed. Repeated elicitation of CH has been used to produce CACD models in mice. We previously showed that the presence of histamine facilitates the creation of eczematous lesions in this model using histidine decarboxylase (HDC) (-/-) mice. Therefore, the effects of histamine on Tregs in the CACD model were investigated in this study. CACD was developed by repeated epicutaneous application of 2, 4, 6-trinitro-1-chlorobenzene (TNCB) on HDC (+/+) and HDC (-/-) murine skin to assess the effects of histamine in CACD. Histamine aggravated CACD in the murine model and suppressed the number of Tregs in the skin. Histamine also suppressed the level of TGF-β1 in this model. Recombinant TGF-β1 or anti-TGF-β1 antibody was injected into the dorsal dermis of HDC (+/+) mice daily just before TNCB challenge to determine the effects of histamine-regulated TGF-β on the Treg population in CACD. Recombinant TGF-β1 injection promoted the infiltration of Tregs in the skin and the production of IL-10; however, anti-TGF-β1 antibody injection suppressed the number of Tregs in the skin and the production of IL-10. Histamine suppresses the number of Tregs in CACD, and this effect is mediated by TGF-β.

  14. A Case of Anaphylactic Reaction Following Matsutake Mushroom Ingestion: Demonstration of Histamine Release Reaction of Basophils

    Directory of Open Access Journals (Sweden)

    Takako Toda

    2010-01-01

    Discussion: Matsutake mushroom can, on rare occasions, cause anaphylaxis in sensitized people, a reaction so far observed only in Japan. Not ony the in vivo prick-to-prick test but also the in vitro basophil activation test utilizing the patient's blood represent useful methods for allergen identification and also for identification of sensitized subjects.

  15. Histamine H(3 receptor-mediated signaling protects mice from cerebral malaria.

    Directory of Open Access Journals (Sweden)

    Walid Beghdadi

    Full Text Available BACKGROUND: Histamine is a biogenic amine that has been shown to contribute to several pathological conditions, such as allergic conditions, experimental encephalomyelitis, and malaria. In humans, as well as in murine models of malaria, increased plasma levels of histamine are associated with severity of infection. We reported recently that histamine plays a critical role in the pathogenesis of experimental cerebral malaria (CM in mice infected with Plasmodium berghei ANKA. Histamine exerts its biological effects through four different receptors designated H1R, H2R, H3R, and H4R. PRINCIPAL FINDINGS: In the present work, we explored the role of histamine signaling via the histamine H3 receptor (H3R in the pathogenesis of murine CM. We observed that the lack of H3R expression (H3R(-/- mice accelerates the onset of CM and this was correlated with enhanced brain pathology and earlier and more pronounced loss of blood brain barrier integrity than in wild type mice. Additionally tele-methylhistamine, the major histamine metabolite in the brain, that was initially present at a higher level in the brain of H3R(-/- mice was depleted more quickly post-infection in H3R(-/- mice as compared to wild-type counterparts. CONCLUSIONS: Our data suggest that histamine regulation through the H3R in the brain suppresses the development of CM. Thus modulating histamine signaling in the central nervous system, in combination with standard therapies, may represent a novel strategy to reduce the risk of progression to cerebral malaria.

  16. Identification and pharmacological characterization of the histamine H3 receptor in cultured rat astrocytes.

    Science.gov (United States)

    Mele, Tina; Jurič, Damijana Mojca

    2013-11-15

    Recently we reported that cultured rat cortical astrocytes express histamine H3 receptor that is functionally coupled to Gi/o proteins and participates to the stimulatory effect of histamine. Due to the lack of data on the distribution of histamine H3 receptors on glial cells we further investigated their presence in cultured astrocytes from different brain regions. Real-time PCR was performed to examine the expression of native histamine H3 receptor in cultured rat astrocytes from cortex,cerebellum, hippocampus and striatum.Double-antigen immunofluorescence staining and[3H]N-α-methylhistamine([3H]NαMH) binding studies were utilized to specifically identify and characterize receptor binding sites in astrocytes. Histamine H3 receptor mRNA was detected in rat astrocytes from all the regions under investigation with the highest levels in striatal astrocytes followed by hippocampal astrocytes and approximately equal levels in cerebellar and cortical astrocytes.Double-antigen immunofluorescence confirmed the presence of histamine H3 receptors on the membrane of all examined astroglial populations.[3H]NαMH bound with high affinity and specificity to an apparently single class of saturable sites on cortical astrocytic membranes(KD¼4.5570.46 nM; Bmax¼5.6370.21 fmol/mg protein)and competition assays with selective agonists and antagonists were consistent with labeling of histamine H3 receptor(range of pKi values 7.50–8.87). Our study confirmed the ability of cultured astrocytes from different rat brain regions to express histamine H3 receptors.The observed diverse distribution of the receptors within various astrocytic populations possibly mirrors their heterogeneity in the brain and indicates their active involvement in histamine-mediated effects.

  17. New developments in histamine and histamine receptors for immunological diseases%组胺及组胺受体对免疫系统调节作用

    Institute of Scientific and Technical Information of China (English)

    钟斐; 蒋瑾瑾

    2013-01-01

    在医学和生物学意义上,组胺是一种重要的生物胺类物质,但它在变态反应性疾病和自身免疫性疾病中的作用仍然知之甚少。近年来,随着组胺及其受体的不断研究,发现它们对免疫功能起着重要的调节作用。尤其是新的组胺受体4(histamine H4 recptor,H4R)的发现和研究,证明其对免疫系统的调节至关重要。这些研究确定了先前不能解释的变态反应炎症和自身免疫性疾病的机制。H4R 可能成为免疫系统调节新的治疗靶点。%Histamine is one of the most important biogenic amines in medicine and biology but its role in allergy and autoimmune has not yet been fully defined. The last few years have brought many discoveries concerning important modulatory effects of histamine and its receptors on basic mechanisms of the immunological processes. The immunomodulatory function of a newly described histamine H4 receptor has been revealed. One of the most important modulatory effects of the histamine currently studied is its influence on immunology. These include finding of previous unappreciated mechanism through which histamine regulated inflammation in allergy, as well as autoimmunity. The H4 histamine receptor has become a major target of novel therapeutics.

  18. Effects of intracerebroventricular histamine injection on circadian activity phase entrainment during rapid illumination changes.

    Science.gov (United States)

    Itowi, N; Yamatodani, A; Mochizuki, T; Wada, H

    1991-02-11

    Histamine is reported to have different effects on shifting the circadian activity phase depending on its circadian administration time (CT). The delay-sensitive period is CT 12-15, and the advance-sensitive period is CT 0-3. The activity phase of rats was entrained by a new light-dark cycle within a week in groups treated with either saline or i.c.v. histamine at CT 12-15. However, on treatment at CT 0-3 the activity phase of the group treated with histamine was entrained by the new light-dark cycle in half the period required for entrainment in the control group.

  19. Effects of histamine on MK-801-induced memory deficits in radial maze performance in rats.

    Science.gov (United States)

    Chen, Z; Zhao, Q; Sugimoto, Y; Fujii, Y; Kamei, C

    1999-08-21

    The effects of histamine on the spatial memory deficits induced by MK-801 were investigated using the eight-arm radial maze paradigm in rats. Intracerebroventricular (i.c.v.) injection of histamine or thioperamide, and intraperitoneal (i.p.) injection of histidine improved the spatial memory deficits induced by MK-801. Similar results were obtained with 2-thiazolylethylamine. In contrast, 4-methylhistamine showed no significant effect. Based on these observations, it seems likely that the protective effect of histamine on MK-801-induced spatial memory deficit is mediated by H(1)-receptors.

  20. Mechanism of the inhibitory effect of endogenous histamine on epilepsy in rats

    Institute of Scientific and Technical Information of China (English)

    ChenZhong

    2004-01-01

    Clinical data demonstrated that long-term epilepsy, especially among children, or ingesting anticonvulsant drugs over time are likely to result in cognitive deficits (e. g. memory or attention problems as well as other CNS side effects such as psychomotor speed abnormalities, somnolence, asthenia, and dizziness. New drug therapy has been expected. The histaminergic neuron system seems to be involved in various physiological and behavioral functions including sleep - wake cycles, stress behavior, neuroendocrine, learning and memory through histamine HI, H2 and H3 receptors. The role of brain histamine in regulating seizure susceptibility has been studied, and a possible anticonvulsant action of endogenous histamine has been postulated

  1. Evidence against Participation of Mast Cell Histamine in Formation of Burn Wound Edema

    Science.gov (United States)

    1982-01-01

    mast cell is the principal source of tissue histamine, the contribution of this cell to edema formation in rats with a standard 30% total body surface area (TBSA) partial-thickness burn was investigated. Degranulating the mast cells prior to burn injury evoked no difference in the amount of edema formed compared with that in rats with normal mast cells. Substantially lower systemic levels of histamine were observed in the plasma of this group of rats after burn injury, which confirmed that degranulation of mast cells affected histamine

  2. De novo generation of histamine in sputum and the effect of antibiotics.

    Science.gov (United States)

    Sheinman, B D; Devalia, J L; Crook, S J; Davies, R J

    1986-03-01

    We have performed experiments to test the hypothesis that bacteria may contribute to the presence of histamine in sputum. Sputum samples obtained from 7 patients with exacerbations of chronic bronchitis and 7 patients with cystic fibrosis were incubated at 37 degrees C for 72 hours. Serial sputum histamine estimations, performed by a recently-developed HPLC technique, showed large, progressive increases in both groups of samples. Both the pre-heating of samples at 100 degrees C prior to incubation and the addition of antibiotics to the incubates substantially reduced these increases. These findings strongly suggest that bacteria may contribute to sputum histamine in infective lung disease.

  3. Antitumor activity of platinum(II) complexes with histamine and radioiodinated histamine in a transplantable murine adenocarcinoma model

    Energy Technology Data Exchange (ETDEWEB)

    Garnuszek, Piotr [Department of Radiopharmaceuticals, National Medicines Institute, 00-725 Warsaw (Poland)], E-mail: pgarnuszek@il.waw.pl; Karczmarczyk, Urszula; Maurin, Michal [Department of Radiopharmaceuticals, National Medicines Institute, 00-725 Warsaw (Poland)

    2008-07-15

    Purpose: Antitumor activity of the dichloroplatinum(II)-histamine complexes labeled with I-125 or I-131 was investigated in a transplantable murine adenocarcinoma (MA) model. Methods: The tumor model was obtained in C3H/W female mice after subcutaneous inoculation of the tumor cells derived from the mice bearing a mammary tumor of spontaneous origin. Antitumor activities of the platinum-histamine complexes were investigated in three independent experiments, which differed in applied doses of preparations (PtCl{sub 2}Hist, PtCl{sub 2}[{sup 125}I]Hist, PtCl{sub 2}[{sup 131}I]Hist, PtCl{sub 2}Hist/PtCl{sub 2}[{sup 125}I]Hist and PtCl{sub 2}Hist/PtCl{sub 2}[{sup 131}I]Hist), treatment schedules as well as stages of the disease progress in the animals used. Experiment 1 included long-term, multidose treatment with low single doses (treatment duration 31-32 days; 8-10 doses of ca. 0.25{center_dot}MTD{sub Pt} each). Experiment 2 included short-term, multidose treatment with higher single doses (4xca. 0.5{center_dot}MTD{sub Pt} up to Day 13 of the treatment). Experiment 3 included long-term concomitant multidose treatment with higher single doses (9x0.9-0.4{center_dot}MTD{sub Pt} up to Day 33). Results: The long-term treatment with the platinum-histamine preparations revealed inhibiting activity on the tumor growth and size in comparison to control groups. The most intensive and significant antitumor effects were observed for the radioactive complexes. The tumor growth delay factors (GDFs) observed in Experiment 1 were 0.4, 0.7, and 1.2 for PtCl{sub 2}Hist, PtCl{sub 2}Hist/PtCl{sub 2}[{sup 131}I]Hist, and PtCl{sub 2}Hist/PtCl{sub 2}[{sup 125}I]Hist, respectively. Significant (P<.05) prolongations of median survivals (MS) were found in Experiment 2 following the treatment with higher single doses of PtCl{sub 2}Hist and PtCl{sub 2}His/PtCl{sub 2}[{sup 125}I]Hist (Ratio MS{sub tr}/MS{sub con} ca. 1.4). A slightly less potent activity was observed for PtCl{sub 2}Hist

  4. The 5-hydroxytryptamine4 receptor agonists prucalopride and PRX-03140 increase acetylcholine and histamine levels in the rat prefrontal cortex and the power of stimulated hippocampal θ oscillations.

    Science.gov (United States)

    Johnson, David E; Drummond, Elena; Grimwood, Sarah; Sawant-Basak, Aarti; Miller, Emily; Tseng, Elaine; McDowell, Laura L; Vanase-Frawley, Michelle A; Fisher, Katherine E; Rubitski, David M; Stutzman-Engwall, Kim J; Nelson, Robin T; Horner, Weldon E; Gorczyca, Roxanne R; Hajos, Mihaly; Siok, Chester J

    2012-06-01

    5-Hydroxytryptamine (5-HT)(4) receptor agonists reportedly stimulate brain acetylcholine (ACh) release, a property that might provide a new pharmacological approach for treating cognitive deficits associated with Alzheimer's disease. The purpose of this study was to compare the binding affinities, functional activities, and effects on neuropharmacological responses associated with cognition of two highly selective 5-HT(4) receptor agonists, prucalopride and 6,7-dihydro-4-hydroxy-7-isopropyl-6-oxo-N-[3-(piperidin-1-yl)propyl]thieno[2,3-b]pyridine-5-carboxamide (PRX-03140). In vitro, prucalopride and PRX-03140 bound to native rat brain 5-HT(4) receptors with K(i) values of 30 nM and 110 nM, respectively, and increased cAMP production in human embryonic kidney-293 cells expressing recombinant rat 5-HT(4) receptors. In vivo receptor occupancy studies established that prucalopride and PRX-03140 were able to penetrate the brain and bound to 5-HT(4) receptors in rat brain, achieving 50% receptor occupancy at free brain exposures of 330 nM and 130 nM, respectively. Rat microdialysis studies revealed that prucalopride maximally increased ACh and histamine levels in the prefrontal cortex at 5 and 10 mg/kg, whereas PRX-03140 significantly increased cortical histamine levels at 50 mg/kg, failing to affect ACh release at doses lower than 150 mg/kg. In combination studies, donepezil-induced increases in cortical ACh levels were potentiated by prucalopride and PRX-03140. Electrophysiological studies in rats demonstrated that both compounds increased the power of brainstem-stimulated hippocampal θ oscillations at 5.6 mg/kg. These findings show for the first time that the 5-HT(4) receptor agonists prucalopride and PRX-03140 can increase cortical ACh and histamine levels, augment donepezil-induced ACh increases, and increase stimulated-hippocampal θ power, all neuropharmacological parameters consistent with potential positive effects on cognitive processes.

  5. Histamine as a Radiosensitizer of Malignant Cell Lines

    Energy Technology Data Exchange (ETDEWEB)

    Rivera, E. S.; Medina, V.; Cricco, G.; Mohamed, N.; Croci, M.; Martin, G.; Nunez, M.; Bergoc, R. M.

    2004-07-01

    It has been established that the treatment with Histamine (Hi) produces a significant growth inhibition of different cell lines derived from human neoplasia. In a model of Knockout mice completely depleted of endogenous Hi, it was observed a significant delay in bone marroe repopulation after whole body irradiation. These results are in agreement with the hypothesis that histamine has a role in the regulation of haematopoiesis as well as an inhibitory effect on apoptosis. The objective of this paper was to study the possible effect of Hi as protector of normal cells and radiosensitizer of malignant ones. To study the effect of Hi on small-intestine and bone marrow, thirty made mice were randomly separeted into two groups: Control irradiated (C), and irradiated receiving Histamine (HI-group). All animals received a single dose of 10 Gy on whole-body employing a ''137Cs source of 189 TB{sub q} (Dose rate: 7.7 Gy/min) calibrated with TLD 700 dosimeter. Hi-group recieved a daily se injection (0.1 mg/kg) starting 20 hs before irradiation. Mice were sacrificed 5 days after irradiation. Histopathological analysis indicated that intestinal mucosae of C group showed important injury, whist mucosae of Hi-treated mice showed mild mucosal atrophy with conservation of villous projections and absence of vascular congestive changes. In order to investigate the effect of Hi on radiosensitivity of transformed cells, MDA-MB-231 (human breast carcinoma cells) were irradiated in vitro with doses ranging from 0 to 10 Gy. Results of radiobiological parameters indicate a significant increase on radiosensitivity of malignant cells. Employing specific fluorescent dyes and flow cytometric analysis we determined that the intracellular levels of hydrogen peroxide (H{sub 2}O{sub 2}) are significant increased by Hi 10 {mu}M in control and also in irradiated MDA-MB-231 cells, while the levels of superoxide (SO{sub 2}) were not significantly modified by Hi-treatment. (Author) 9 refs.

  6. HISTAMINE IN CANNED SARDINES HISTAMINA EM CONSERVAS DE SARDINHA

    Directory of Open Access Journals (Sweden)

    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,