Sample records for accumulation histamine release

  1. Induction of mast cell accumulation, histamine release and skin edema by N49 phospholipase A2

    Mo Ya-Zhen


    Full Text Available Abstract Background It has been recognized that phospholipase A2 (PLA2 is a crucial component of snake venom, which contributes greatly to snake venom induced inflammation in man. However, the mechanisms through which N49 PLA2 provoke inflammation remain unclear. Recently, a N49 PLA2, TM-N49 from Protobothrops mucrosquamatus crude venom was characterized in our laboratory. Since the purification procedure developed is able to supply us with relatively large quantity of highly purified TM-N49, we investigated the ability of TM-N49 in induction of inflammation. Results The results showed that TM-N49 provoked a dose dependent increase in microvascular leakage in the skin of rats. The potency of TM-N49 in induction of skin edema appeared similar potency of bradykinin and histamine. Pretreatment of rats with compound 48/80 diminished TM-N49 induced skin reaction and reduced mast cell numbers in rats. Ginkgolide B and cyproheptadine, but not terfenadine and quinacrine, inhibited TM-N49 elicited microvascular leakage when they were co-injected with the stimulus to rat skin. Moreover, TM-N49 was found to induce histamine release from human colon, lung and tonsil mast cells, and both metabolic inhibitors and pertussis toxin were capable of inhibiting TM-N49 elicited histamine release. TM-N49 induced mast cell accumulation in the peritoneum of mice, which was inhibited by co-injection of ginkgolide B, cyproheptadine and terfenadine. Intravenous injection of monoclonal antibodies against CD18, ICAM-1 and CD11a also blocked TM-N49 induced mast cell accumulation. Conclusion TM-N49 is a potent stimulus for skin edema, mast cell activation and accumulation.

  2. Histamine release from cord blood basophils

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


    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...... stimulated by the calcium ionophore A 23187 was found to be highly dependent on the storage time of the EDTA-anticoagulated blood samples, which should be carefully controlled....

  3. Homogeneous time resolved fluorescence assay to measure histamine release.

    Claret, Emmanuel J; Ouled-Diaf, Josy; Seguin, Patrick


    Histamine is a biogenic amine synthesized by the enzymatic decarboxylation of histidine. Implication of histamine in allergy is well described but histamine is also found in some specific neurones, functions as a neurotransmitter and regulates sleep/wake cycles, hormonal secretion, cardiovascular control and thermo-regulation. We have developed a TR-FRET histamine assay, based on the competition between sample histamine and allophycocyanine (XL665) labelled histamine for binding to a Europium cryptate (EuK) labelled antibody. As histamine is a small monoamine molecule, high affinity antibodies have been raised against carrier protein conjugated histamine. Therefore, sample histamine needs to be derivatized in the same way as the conjugated histamine, so that the antibody will have a similar affinity for both molecules. This acylation step is performed directly in wells and does not need to be done in separate vials, making handling easier for large numbers of samples. The incubation takes place at room temperature for 3 hours. The assay covers a measurement range of 1.56 to 400 nM and shows an analytical sensitivity of 1.3nM. We have shown that miniaturization of sample and reagents volumes down to 20 micro l does not alter these performances. This histamine release assay provides a particularly well adapted procedure for HTS and secondary screening compared to current heterogeneous methods. PMID:14683484

  4. Blood histamine release: A new allergy blood test

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

  5. Inhibitory effect of the CA2+ antagonist nifedipine on histamine release from rat peritoneal mast cells.



    Full Text Available 45Ca uptake and histamine release was examined in mast cells from rats sensitized with ovalbumin and Bordetella Bertussis as an adjuvant. The uptake of 45Ca by the mast cells was significantly increased by stimulation with ovalbumin as was the release of histamine from the mast cells. Nifedipine, a calcium antagonist, inhibited the increase in both 45Ca uptake and histamine release stimulated by ovalbumin, though the effect on 45Ca uptake was stronger than that on histamine release.

  6. Inhibitory effect of the CA2+ antagonist nifedipine on histamine release from rat peritoneal mast cells.

    Tanizaki,Yoshiro; Komagoe,Haruki; Sudo,Michiyasu; Ohtani,Jun; Kimura,Ikuro; Akagi,Katsumi; Townley, Robert G.


    45Ca uptake and histamine release was examined in mast cells from rats sensitized with ovalbumin and Bordetella Bertussis as an adjuvant. The uptake of 45Ca by the mast cells was significantly increased by stimulation with ovalbumin as was the release of histamine from the mast cells. Nifedipine, a calcium antagonist, inhibited the increase in both 45Ca uptake and histamine release stimulated by ovalbumin, though the effect on 45Ca uptake was stronger than that on histamine release.

  7. Characterization of histamine receptors mediating the stimulation of cyclic AMP accumulation in rabbit cerebral cortical slices.

    Al-Gadi, M.; Hill, S. J.


    The characteristics of histamine-stimulated adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulation in slices of rabbit cerebral cortex have been investigated. The selective H2-receptor antagonists, cimetidine, tiotidine, metiamide and ranitidine appeared to antagonize the stimulation of cyclic AMP accumulation elicited by histamine in a competitive manner consistent with an interaction with histamine H2-receptors. The H1-receptor antagonist mepyramine (0.8 microM) produced only a weak...

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

    Raininko, R.


    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.

  9. Study on histamine release in lung tissue of rats after irradiation

    In order to study a relationships between radiation induced histamine release and radiation pneumonitis. Histamine levels in the lung tissue of wister rats after whole lung irradiation were investigated through fluorometric assay. The results showed that a peak histamine level occurred within 30 min after irradiation of 274 rads. When the thymus of the rat was protected from radiation histamine in the lung tissue was not released. This investigation of fluorometric assay shows high histamine levels in the lung tissue after irradiation and suggests that radiation treatment of the thymus may induce histamine release. (auth.)

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

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


    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...

  11. Effect of methylmercury on histamine release from rat mast cells

    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)


    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.)

  12. Effect of a serum factor on IgE-mediated histamine release from whole blood.

    Tanizaki,Yoshiro; Komagoe,Haruki; Sudo,Michiyasu; Morinaga, Hiroshi; Nakagawa,Saburo; Kitani,Hikaru; Takahashi, Kiyoshi; Kimura,Ikuro


    IgE-mediated histamine release from whole blood was analyzed in 44 patients with bronchial asthma by observing maximum present release and dose-response curves of histamine release induced by anti-IgE and house dust extract. The maximum histamine release from whole blood induced by anti-IgE correlated with total serum IgE levels. There was a close correlation between allergen-induced release from whole blood and the serum levels of specific IgE antibodies. In the maximum histamine release fro...

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

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


    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 cau...

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

    Jensen, C; Svendsen, U G; Thastrup, Ole; Stahl Skov, P; Leon, A; Norn, S

    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...... acid moieties, was more potent than gangliosides with 2 moieties (GD1a and GD1b), which again were more potent inhibitors than GM1 with one moiety. Asialo-GM1 was without effect. In high concentrations the gangliosides potentiated basophil histamine release. The modulation of histamine release was...

  15. Histamine H3 receptors regulate acetylcholine release from the guinea pig ileum myenteric plexus

    The effect of selective histamine H3-receptor agonists and antagonists on the acetylcholine release from peripheral nerves was evaluated in the guinea pig longitudinal muscle-myenteric plexus preparations, preloaded with (3H)choline. In the presence of H1 and H2 blockade, histamine and (R)-α-methylhistamine inhibited the electrically-evoked acetylcholine release, being (R)-α-methylhistamine more active than histamine, but behaving as a partial agonist. The effect of histamine was completely reversed by selective H3-blocking drugs, thioperamide and impromidine, while only submaximal doses of (R)-α-methylhistamine were antagonized. Furthermore, thioperamide and impromidine enhanced the electrically-evoked acetylcholine release. On the contrary, the new H3-blocker, HST-7, was found substantially ineffective, both as histamine antagonist and as acetylcholine overflow enhancer. These data suggest that histamine exerts an inhibitory control on the acetylcholine release from intestinal cholinergic nerves through the activation of H3 receptors

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

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

  17. Pasteurella haemolytica leukotoxin induces histamine release from bovine pulmonary mast cells.

    Adusu, T E; Conlon, P D; Shewen, P.E.; Black, W D


    Pasteurella haemolytica A1 leukotoxic culture supernatant was evaluated for its ability to induce histamine release from bovine pulmonary mast cells isolated by enzymatic dispersion of lung tissue. Histamine was measured by a radioimmunoassay technique. Leukotoxic culture supernatant of P. haemolytica significantly released histamine in a time and concentration-related manner. This effect was lost when culture supernatant was heat-inactivated or preincubated with leukotoxin neutralizing rabbi...

  18. Human, recombinant interleukin-2 induces in vitro histamine release in a dose-dependent manner

    Nielsen, Hans Jørgen; Petersen, L J; Skov, P S


    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...

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

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


    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...

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

    Knudsen, T; Ferjan, I; Johansen, Torben

    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...... enhanced the histamine release while digitoxigenin either had no effect or was slightly inhibitory. In the presence of calcium, the glycosides only affected potassium uptake and histamine release slightly. In the presence of lithium or lanthanum the enhancement of the histamine release was counteracted....... Hydrophilic digitalis glycosides seem to enhance histamine release secondary to an increase in intracellular sodium. Lipophilic glycosides have no effect on the release....

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

    Johansen, Torben


    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...

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

    Johansen, Torben


    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...

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

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


    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...

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

    Garland, L G; Johansen, Torben


    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....... 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...

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

    Petersen, Lars J; Pedersen, Juri L; Skov, Per S;


    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...... (baseline 11.6 +/- 1.8 nM vs. post-burn values of 14.8 +/- 1.8 nM, n = 8). CONCLUSIONS: Histamine is not released in human skin during the acute phase of a thermal injury....

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

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


    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.

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


    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

  8. Apomorphine-induced inhibition of histamine release in rat peritoneal mast cells.

    Battistella, A.; Boarato, E.; Bruni, A; Mietto, L.; Palatini, P.; Toffano, G.


    The apomorphine-induced inhibition of histamine release in rat peritoneal mast cells was studied by means of secretagogues stimulating different pathways of mast cell activation. Apomorphine inhibited the mast cell response to all releasing agents (lysophosphatidylserine plus nerve growth factor, compound 48/80, substance P, ATP, tetradecanoylphorbolacetate, melittin). The IC50 ranged from 4 microM to 24 microM at concentrations of secretagogues releasing 30-50% of mast cell histamine. Howeve...

  9. Roles of intracellular Ca2+ and cyclic AMP in mast cell histamine release induced by radiographic contrast media.

    Saito, Mami; Itoh, Yoshinori; Yano, Takahisa; Sendo, Toshiaki; Goromaru, Takeshi; Sakai, Naoko; Oishi, Ryozo


    Mast cell histamine release is considered to be associated with the etiology of anaphylactoid reactions to iodinated radiographic contrast media (RCM). In the present study, the effects of various ionic and non-ionic RCM on histamine release from mast cells were compared, and the possible mechanisms of the histamine release were subsequently determined. Both ionic (ioxaglate and amidotrizoate) and non-ionic (iohexol, ioversol, iomeprol, iopamidol and iotrolan) RCM increased histamine release from the dissociated rat pulmonary cells, whereby ionic materials were more potent than non-ionic agents. There was no significant correlation between the extent of histamine release and the osmolarity of each RCM solution. In addition, hyperosmotic mannitol solution (1000 mOsm/kg) caused no marked histamine release. Thus, it is unlikely that the hyperosmolarity of RCM solutions contributes to the histamine release. RCM also stimulated, but to a lesser extent, the histamine release from rat peritoneal cells. The RCM-induced histamine release from both types of cells was inhibited by dibutyl cyclic AMP or combined treatment with forskolin and 3-isobutyl-1-methylxanthine. Corresponding to these results, RCM markedly reduced the cellular cyclic AMP content. On the other hand, the removal of intracellular but not the extracellular Ca2+ attenuated the RCM-induced mast cell histamine release. From these findings, it is suggested that the decrease in cellular cyclic AMP content and an increase in intracellular Ca2+ contribute at least in part to the RCM-induced mast cell histamine release. PMID:12690428

  10. Activation of sensory nerves participates in stress-induced histamine release from mast cells in rats.

    Huang, Z L; Mochizuki, T; Watanabe, H; Maeyama, K


    To elucidate the mechanism by which stress induces rapid histamine release from mast cells, Wistar rats, pretreated as neonates with capsaicin, were subjected to immobilization stress for 2 h, and histamine release was measured in paws of anesthetized rats by using in vivo microdialysis after activation of sensory nerves by electrical or chemical stimulation. Immobilization stress studies indicated that in control rats stress induced a 2.7-fold increase in the level of plasma histamine compared to that in freely moving rats. Whereas pretreatment with capsaicin significantly decreased stress-induced elevation of plasma histamine. Microdialysis studies showed that electrical stimulation of the sciatic nerve resulted in a 4-fold increase of histamine release in rat paws. However, this increase was significantly inhibited in rats pretreated with capsaicin. Furthermore, injection of capsaicin into rat paw significantly increased histamine release in a dose-dependent manner. These results suggest that activation of sensory nerves participates in stress-induced histamine release from mast cells. PMID:10462124

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

    Nielsen, Hans Jørgen; Edvardsen, L; Vangsgaard, K; Dybkjaer, E; Skov, P S


    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...... full amount of leucocytes, and this may play a significant role in detrimental effects of blood transfusion....

  12. Histamine is released from skin by substance P but does not act as the final vasodilator in the axon reflex.

    Barnes, P J; Brown, M. J.; Dollery, C. T.; Fuller, R W; Heavey, D. J.; Ind, P. W.


    We have explored in man the hypothesis that histamine released from dermal mast cells by neurotransmitters from afferent nerves contributes to vasodilatation of the axon reflex. The ability of substance P to release histamine from human skin in vivo, and the effects of a histamine H1-receptor antagonist on capsaicin-induced axon reflex flares were studied. Intradermal injections of substance P (50 pmol) produced a weal and flare response which was associated with increased histamine concentra...

  13. Cardiac mast cells regulate myocyte ANP release via histamine H2 receptor in beating rabbit atria.

    Li, Dan; Wen, Jin Fu; Jin, Jing Yu; Quan, He Xiu; Cho, Kyung Woo


    It has been shown that histamine inhibits atrial natriuretic peptide (ANP) release. Because cardiac mast cells are the principal source of histamine in the heart, we hypothesized that cardiac mast cells are involved in the regulation of atrial ANP release. To test the hypothesis, experiments were performed in perfused beating rabbit atria allowing atrial pacing and measurements of changes in atrial stroke volume, intraatrial pulse pressure and myocyte ANP release. Mast cell degranulation with Compound 48/80 decreased atrial myocyte ANP release, and the response was blocked by a selective histamine H(2) receptor blocker, cimetidine, indicating that histamine was responsible for the decrease in ANP release. Mast cell stabilization with cromolyn blocked the Compound 48/80-induced decrease in ANP release. These data suggest that mast cell-derived histamine is involved in the regulation of cardiac ANP release. Thus, the cardiac mast cell-cardiomyocyte communication via the histamine-ANP pathway may implicate in the cardiac disorder associated with mast cell degranulation such as in acute coronary syndrome or cardiac hypertrophy. PMID:19328828

  14. Inhibition of cortical acetylcholine release and cognitive performance by histamine H3 receptor activation in rats.

    Blandina, P.; Giorgetti, M.; L. Bartolini; M.Cecchi; Timmerman, H.; Leurs, R.; Pepeu, G; Giovannini, M. G.


    1. The effects of histamine and agents at histamine receptors on spontaneous and 100 mM K(+)-evoked release of acetylcholine, measured by microdialysis from the cortex of freely moving, rats, and on cognitive tests are described. 2. Local administration of histamine (0.1-100 microM) failed to affect spontaneous but inhibited 100 mM K(+)-stimulated release of acetylcholine up to about 50%. The H3 receptor agonists (R)-alpha-methylhistamine (RAMH) (0.1-10 microM), imetit (0.01-10 microM) and im...

  15. Potentiation of Vancomycin-Induced Histamine Release by Muscle Relaxants and Morphine in Rats

    Shuto, Hideki; Sueyasu, Masanori; Otsuki, Shuji; Hara, Tomoko; Tsuruta, Yuki; Kataoka, Yasufumi; Oishi,Ryozo


    The intravenous injection of vancomycin sometimes causes anaphylactoid reactions, in which histamine release may play a major role. These reactions are more frequently manifested when vancomycin is injected into anesthetized patients. We examined the vancomycin-induced histamine release and the interaction of vancomycin with muscle relaxants or opioid in rats. In an in vitro study with rat peritoneal mast cells, treatment with vancomycin at concentrations of greater than 1.25 mM produced sign...

  16. FK506 inhibition of histamine release and cytokine production by mast cells and basophils.

    Sengoku, T; Kishi, S; Sakuma, S; Ohkubo, Y; Goto, T


    Histamine release and cytokine production by mast cells and basophils are thought to be closely involved in the pathogenesis of allergic diseases. Some reports show that FK506 (tacrolimus hydrate) inhibited histamine release and cytokine production by mast cells and basophils. However, as the effects of FK506 has not been compared with those of clinically used drugs in those reports, the clinical relevancy of FK506 inhibition remained unclear. In this paper, we compared the actions of FK506 with those of steroids or disodium cromoglycate (DSCG) which has been clinically used. FK506 inhibited histamine release by Brown-Norway rat peritoneal mast cells more potently than steroids and especially DSCG. FK506 also inhibited histamine release by a mast rat basophilic leukemia (RBL)-1 cell line and human peripheral blood basophils, whereas steroids failed to inhibit histamine release by human basophils. FK506 as well as steroids inhibited TNF-alpha and IL-4 production by RBL-1 cells. FK506 was therefore more effective than steroids and DSCG in inhibiting histamine release, and it also had the ability of inhibiting cytokine production by mast cells as steroids do. We concluded that FK506 might regulate allergic diseases via these actions, judging from the viewpoint of clinical relevancy. PMID:10685002

  17. Human, recombinant interleukin-2 induces in vitro histamine release in a dose-dependent manner

    Nielsen, Hans Jørgen; Petersen, L J; Skov, P S


    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...... 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 < 0.05) after 1 hour stimulation, and no further increase was observed after 24 and 48 hours, respectively. Histamine concentration increased...

  18. Involvement of histamine released from mast cells in acute radiation dermatitis in mice

    A possible involvement of histamine in acute radiation dermatitis in mice was investigated. The dose of 40 Gy of gamma irradiation induced erythema and edema in C57BL/6 mice treated with vehicle. However, in C57BL/6 mice treated with chlorpheniramine and WBB6F1-W/WV mice, erythema and edema were not observed. In all of these mice, epilation and dry desquamation were induced, but bepotastine significantly reduced the extent of these areas. These results suggest that gamma irradiation-induced erythema and edema were caused by histamine released from mast cells via histamine H1 receptor, and epilation was induced by other inflammatory mediators. (author)

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

    Shao-Heng He; Hua Xie


    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.

  20. Lymphatic diamine oxidase secretion stimulated by fat absorption is linked with histamine release

    JI Yong; Sakata, Yasuhisa; Li, Xiaoming; Zhang, Chao; Yang, Qing; Xu, Min; Wollin, Armin; Langhans, Wolfgang; Tso, Patrick


    Diamine oxidase (DAO) is abundantly expressed in mammalian small intestine catalyzing the oxidative breakdown of polyamines and histamine. The aim of this study was to determine the relationship between stimulation of intestinal diamine oxidase secretion with intestinal fat absorption and histamine release. Conscious intestinal lymph fistula rats were used. The mesenteric lymph ducts were cannulated and intraduodenal tubes were installed for the infusion of Liposyn II 20% (an intralipid emuls...

  1. Suppressed histamine release from rat peritoneal mast cells by ultraviolet B irradiation: decreased diacylglycerol formation as a possible mechanism

    This study was designed to investigate the effect of ultraviolet B (UVB) irradiation on mast cell functions. Purified mast cells obtained from rat peritoneal cavity were irradiated with UVB and subsequently exposed to a degranulator, compound 48/80, or the calcium ionophore A-23187. The amount of histamine released from mast cells measured by the enzyme isotopic assay was significantly decreased by UVB irradiation (100-400 mJ/cm2). Within this dose range, UVB alone was not cytotoxic to the cells because it did not induce histamine release. The suppression was observed when mast cells were subjected to degranulation without intervals after UVB irradiation, and even after 5 h postirradiation. The wavelength of 300 nm from a monochromatic light source showed the maximum effect. When mast cells prelabeled with [3H]arachidonate were irradiated and challenged by compound 48/80, label accumulation in diacylglycerol produced by the phosphatidylinositol cycle was considerably decreased by UVB irradiation. From these results, we hypothesize that, within an adequate irradiation dose, UVB irradiation suppresses histamine release from mast cells, probably by causing noncytotoxic damage to the membrane phospholipid metabolism, which is tied to the degranulation mechanisms

  2. Inhaled nedocromil sodium reduces histamine release from isolated large airway segments of asthmatic subjects in vivo.

    Maxwell, D L; Hawksworth, R J; Lee, T H


    Placement of an intrabronchial single balloon catheter provides the possibility of measuring histamine release in isolated large airway segments in vivo. We wanted to assess the protective effect of nedocromil sodium on intrabronchial histamine release after hyperosmolar challenge. Six mild asthmatics were bronchoscoped 30 min after inhalation of 4 mg nedocromil sodium or placebo, given via a metered dose inhaler in a randomized, double-blind, cross-over study. Lavage of the left main bronchus was carried out proximal to a balloon catheter inflated at its bifurcation, and specimens were assayed for histamine and prostaglandin D2 (PGD2) by radioimmunoassay. The rise in histamine concentration in bronchial epithelial fluid following hyperosmolar saline challenge was significantly greater following placebo than following nedocromil sodium (mean +/- SEM prechallenge histamine concentration on placebo day 6.9 +/- 2.9 nM; post-challenge: 25.3 +/- 8.0 nM; mean +/- SEM prechallenge histamine concentration on the day nedocromil sodium was given: 3.7 +/- 0.7 nM; post-challenge 5.8 +/- 1.7 nM). Changes in PGD2 levels reflected the changes in histamine, but the variability of response was large, and there were no significant differences between the effects of placebo and nedocromil sodium. The procedure caused significantly greater falls in peak expiratory flow rates following placebo (mean +/- SEM percentage fall 20.2 +/- 4.4%) than following nedocromil sodium (0.9 +/- 5.8%, p airways, and that nedocromil sodium inhibits histamine release from mediator cells in vivo. PMID:7693506

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

    Dalgaard, Emil G; Andersen, Kenneth; Svenningsen, Per; Hansen, Pernille B L


    AIMS: The aims were to develop a method for real-time detection of histamine release and to test if incubation with aldosterone induces histamine release from isolated, perfused mice mesenteric arteries. METHODS: Fura-2 loaded HEK-293 cells transfected with the histamine H1 receptor was used 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...

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

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


    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...... was abolished, whereas the inhibition by verapamil or lanthanum was unaffected. This difference may be explained by the different mode of action of the calcium channel antagonists, and the results suggest an association between membrane sialic acid and the calcium channel....

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

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


    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. PMID:25468497

  6. Staphylococcus aureus and influenza A virus stimulate human bronchoalveolar cells to release histamine and leukotrienes

    Clementsen, P; Bisgaard, H; Pedersen, M;


    Mediator release was examined from superficially lying cells in the airway epithelium obtained by bronchoalveolar lavage (BAL) in 13 non-atopic individuals. The BAL-cells were incubated (20 min, 37 degrees C) with Staphylococcus (Staph.) aureus or with human influenza A virus Staph. aureus...... 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...

  7. Histamine in the central nervous system: characterization of release and effects of other neurotransmitters on the activity of histaminergic neurons

    The release of endogenous histamine and the involvement of adrenergic, dopaminergic and glutamatergic neurons in the modulation of histamine release was investigated by the push-pull technique. The posterior hypothalamus of conscious rats was superfused through a push-pull cannula with artificial cerebrospinal fluid containing neuroactive compounds. Histamine was determined radioenzymatically or by HPLC with fluorimetric detection. Experiments with depolarizing, channel-blocking and enzyme-inhibiting agents proved the neuronal origin of the histamine analysed. Superfusion with agonists and antagonists of α-adrenoceptors led to the conclusion that under in vivo conditions the neuronal histamine released is modulated by noradrenergic α2-adrenoceptors in a negative way, but not by β-adrenoceptors. Findings with dopaminergic agents suggested that dopaminergic neurons of the hypothalamus influence the release of histamine in a dual way: D2-heteroreceptors stimulate, D3-heteroreceptors inhibit the release. The anterior and medial hypothalamus possess glutamate-heteroreceptors, which modulate the histamine release in a positive way. We further studied the influence of the GABA- and NO-system on the manifestation of genetic hypertension and connections to the histaminergic system. The chronical activation of both systems led to distinct effects on blood pressure and histamine contents of main brain areas of normo- and hypertensive rats (WKY, SHR). However, a primary contribution of both systems to the manifestation of hypertension must be excluded. (author)

  8. Comparative effect of recombinant IL-1, -2, -3, -4, and -6, IFN-gamma, granulocyte-macrophage-colony-stimulating factor, tumor necrosis factor-alpha, and histamine-releasing factors on the secretion of histamine from basophils

    Most cytokines possess multiple biologic activities. This study was undertaken to investigate the effect of rIL-1 beta, -2, -3, -4 and -6, IFN-gamma, TNF-alpha, and granulocyte-macrophage (GM)-CSF on basophils from 16 donors and the amount of histamine released was compared with that by partially purified mononuclear cell-derived histamine-releasing factor (HRF) and anti-IgE. We found that only IL-3 and GM-CSF at relatively high doses (50 to 500 ng/ml) released small amounts of histamine (3 to 14%) from two allergic donors. In contrast, both HRF and anti-IgE released significant amounts of histamine from all donors. Other cytokines did not release any measurable quantity of histamine. Simultaneous addition of several cytokines to the basophils also failed to release histamine. IL-3, GM-CSF, and IL-1 can also release histamine at lower concentrations (less than 5 ng/ml) when incubated with basophils in the presence of D2O. Basophils from 6 out of 13 allergic donors released histamine in response to IL-3, whereas three donors responded to IL-1 beta and two responded to GM-CSF. The results of this study demonstrated that although IL-3 and GM-CSF release small amounts of histamine only from a select group of allergic patients, mononuclear cell-derived HRF is more potent in their action and release histamine from normals as well as allergic patients

  9. Effect of amiloride on arachidonic acid and histamine release from rat mast cells

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


    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...

  10. Dependence of anaphylactic histamine release from rat mast cells on cellular energy metabolism

    Johansen, Torben


    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...

  11. Basophil response to antigen and anti-IgE 3. Ca(2+) influx and histamine release

    Tanizaki,Yoshiro; Kitani,Hikaru; Okazaki, Morihiro; Mifune, Takashi; Mitsunobu, Fumihiro; Kimura,Ikuro


    The release mechanism of chemical mediators from basophils and mast cells was discussed when these cells were stimulated by different antigens and anti-IgE. 1. Ca(2+) influx into mast cells increased after stimulation by antigen. The increased Ca(2+) uptake by mast cells was inhibited by antiallergic agents, disodium cromoglycate (DSCG) and tranilast, and calcium antagonists, nifedipine and nicardipine. 2. The dose-response curve of histamine release by antigen was different from that by anti...

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

    Johansen, Torben


    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...... The observations are consistent with the view that energy requiring processes are involved in ionophore-induced histamine release from rat mast cells although part of the ATP reduction in the aerobic experiments may be due to an uncoupling effect of calcium on the oxidative phosphorylation....

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

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

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

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

  15. Histamine, histamine intoxication and intolerance.

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


    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. PMID:26242570

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

    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 3H-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

  17. Inhibition of anaphylactic histamine release from heterologously sensitized mast cells: differential effects of drugs which interfere with calcium influx.

    Kurose, Masao


    Drug effects were studied on anaphylactic histamine release from rat mast cells sensitized in vitro with mouse IgE antibody. When histamine release was elicited by adding Ca-++ at various times after antigen-stimulation of sensitized cells in Ca++-free medium, the drugs to be tested were added shortly before each Ca++ addition. Quercetin was effective only when added before or immediately after antigen. Theophylline and disodium cromoglycate (DSCG) were active irrespective of the time interva...

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

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


    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

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

    Nolte, Hendrik; Spjeldnæs, Nikolaj; Kruse, Aksel; Nielsen, Bent Windelborg


    macroscopically inflamed and normal tissue. Mast cells and corresponding basophils were challenged with anti-IgE, anti-IgG, subclass anti-IgG4, and formyl-methionyl-leucyl-phenylalanine (FMLP) and results were compared with those from nine patient control subjects. The mast cell count in patients with ulcerative...... histamine per sample at anti-IgG4 challenge; however, the corresponding basophils did not respond to anti-IgG4. In addition, the anti-IgG4 mediated histamine release was primarily confined to patients with inflammatory bowel disease. This study substantiates previous histopathological findings that mast...... cells may play a functional role in the inflammatory process of inflammatory bowel diseases and provides evidence for a possible role of subclass IgG4 as a reaginic antibody....

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

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


    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'. PMID:26169221

  1. Aortic endothelial and smooth muscle histamine metabolism. Relationship to aortic 125I-albumin accumulation in experimental diabetes

    We studied rat aortic endothelial and smooth muscle cell de novo histamine synthesis mediated by histidine decarboxylase (HD) and the effects of its inhibition by alpha-hydrazinohistidine on the intracellular histamine content and intraaortic albumin accumulation in streptozotocin-induced diabetes. Diabetes was induced by a single jugular vein injection of streptozotocin (60 mg/kg, pH 4.5, ether anesthesia), with animals held 4 weeks following the overt manifestation of diabetes. Additional diabetic and nondiabetic rats received alpha-hydrazinohistidine (25 mg/kg, i.p. every 12 hours) during the last week; this had no effect on the severity of diabetes in any animal receiving streptozotocin. Data indicate that the aortic endothelial (EC) HD activity was increased more than 130% in the untreated diabetic group but was similar to control values in the diabetic group receiving alpha-hydrazinohistidine; similarily, the EC histamine content from diabetic aortas increased 127% over control values, but in EC from diabetic animals receiving alpha-hydrazinohistidine it was comparable to control values. Similar trends were observed for the subjacent aortic smooth muscle. In untreated diabetic animals the aortic 125I-albumin mass transfer rate was increased 60% over control values, while in diabetic animals receiving alpha-hydrazinohistidine the 125I-albumin mass transfer rate was essentially identical to controls. These data indicate that in streptozotocin diabetes there is an expansion of the inducible aortic histamine pool, and that this expansion is intimately related to the increased aortic albumin accumulation

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

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


    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...... ciclosporin because they were H1 anti-histamine unresponsive. CSU patients with a positive BHRA were more likely to respond clinically (P...

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

    Johansen, Torben


    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 a......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...

  4. IgE-mediated histamine release from nasal mucosa is inhibited by SLPI (secretory leukocyte protease inhibitor to the level of spontaneous release

    U. Westin


    Full Text Available The secretory leukocyte protease inhibitor (SLPI is a low-molecular-weight inhibitor of proteases, such as elastase and cathepsin G which are released from leukocytes during phagocytosis. The purpose of this study was to determine whether or not SLPI is able to inhibit IgE-mediated histamine release. Nasal mucosa from 11 test subjects without atopic disposition was used for this in vitro study. We found that SLPI inhibited histamine release in a dose-dependent way but was without influence on the spontaneous release.

  5. Dual effects of protoporphyrin and long wave ultraviolet light on histamine release from rat peritoneal and cutaneous mast cells

    In this study we investigated the effects of long wave ultraviolet light (UVA) and various doses of protoporphyrin (PP) on the release of histamine from rat peritoneal and cutaneous mast cells. We also correlated these results with morphologic characteristics and viability of the cells. PP at a dose of 30 ng/ml plus UVA-induced negligible histamine release from rat peritoneal mast cells (RPMC), but was able to suppress the ability of the cells to release histamine in response to subsequent exposure to the calcium ionophore A23187, compound 48/80, or the combination of Ag and IgE. This functional change was associated with an increase in cell size, and cell lysis that gradually occurred during 24 h in culture. PP at a dose of 3 ng/ml plus UVA also significantly inhibited secretogogue-induced histamine release from rat peritoneal mast cells, but this dose was not associated with significant changes in morphology or viability. These various effects of PP plus UVA were also observed with mast cell preparations obtained by the enzymatic dispersion of rat skin. The suppression of secretogogue-induced histamine release in rat peritoneal mast cells treated with PP (3 ng/ml) and UVA could not be reversed by culturing the cells in the dark for 24 h in the absence of PP. Unlike the direct cytotoxic histamine releasing action of high doses of PP plus UVA, the suppressive effect of low PP doses could not be inhibited by catalase, but could be reduced by the absence of calcium. Our results indicate that PP plus UVA has dual effects on mast cells, apparently involving distinct mechanisms. This implies the possibility that PP and UVA at appropriate doses could be used in photochemotherapy of mast cell-mediated skin diseases

  6. Pyrazolopyrimidines: synthesis, effect on histamine release from rat peritoneal mast cells and cytotoxic activity.

    Quintela, J M; Peinador, C; Moreira, M J; Alfonso, A; Botana, L M; Riguera, R


    A series of 1H-pyrazolo[3,4-d]pyrimidines (3--6) substituted at positions 1 (R(1)=Ph, H, tert-butyl and ribosetribenzoate), 4 (R(2)=chlorine, nitrogen and oxygen nucleophiles), and 6 (dimethylamino) have been synthesized and their effect on the release of histamine from rat peritoneal mast cells measured. After chemical stimulation, (polymer 48/80), several compounds (i.e. 3b, 4a, 4b, 4d, 4g, 5a), produce inhibition two to three times higher (40--60%) than DSCG but this action is lower after preincubation. 4b (R(1)=Ph, R(2)=NHCH(2)Ph; 50--70% inhibition) and 5a (R(1)=H, R(2)=OMe; 50--55% inhibition) are the most active ones in both experiments. With ovoalbumin as stimulus, several pyrazolopyrimidines show inhibition similar to DSCG, the most active compounds being 6a--d (IC(50)=12--16 microM; R(1)=ribosetribenzoate, R(2)=methoxy and amino). Compounds 4e (R(1)=t-butyl, R(2)=OMe) and 4g (R(1)=t-butyl, R(2)=piperidino) are inducers of the release of histamine (60 and 150% increase). Compounds 4b and 4c showed cytotoxic activity (IC(50)=1 microg/mL) to HT-29 human colon cancer cells. PMID:11461757

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

    Fukugasako, Sanae; ITO, SHINICHI; Ikemoto, Yoshimi


    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...

  8. Adenosine triphosphate levels during anaphylactic histamine release in rat mast cells in vitro. Effects of glycolytic and respiratory inhibitors

    Johansen, Torben


    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...... related to the histamine release process and not to an uncoupling of oxidative phosphorylation by an increased concentration of cytosol Ca2+. The ATP content of the cells was not restored within the 2 h of observation. No inhibition of lactate production from mast cells exposed to antigen in the presence...

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

    Johansen, Torben


    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...

  10. The effects of thermal stimuli on intracellular calcium change and histamine releases in rat basophilic leukemia mast cells

    Wu, Zu-Hui; Zhu, Dan; Chen, Ji-Yao; Zhou, Lu-Wei


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



    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.

  12. Modulation of human basophil histamine release by protein kinase C inhibitors differs with secretagogue and with inhibitor.

    Bergstrand, H; Lundquist, B; Karabelas, K; Michelsen, P


    To assess possible involvement of protein kinase C (PKC) in human basophil degranulation, the present work compared effects of various purported PKC inhibitors on leukocyte histamine release triggered by different stimuli. The effects recorded varied with the inhibitor and the secretagogue used; moreover, with a given secretagogue, different inhibitors often displayed different activities. Thus, histamine release triggered by the PKC activator 4 beta-phorbol 12-myristate 13-acetate was blocked by K252a, staurosporine and the purported specific PKC inhibitor Ro 31-7549, and reduced by calphostin C, H-7, TMB-8 and W-7 but not affected by polymyxin B; it was augmented by 2.1 microM palmitoyl carnitine. The leukocyte response induced by another putative activator of PKC, 1,2-isopropylidene-3-decanoyl-sn-glycerol, was also enhanced by 2.1 microM palmitoyl carnitine, slightly increased by staurosporine, TMB-8 and W-7 but not affected by calphostin C, H-7, K252a or Ro 31-7549, whereas the hyperosmolar mannitol-induced response was reduced by H-7, calphostin C, TMB-8 and W-7 and slightly augmented by staurosporine. Anti-IgE-induced histamine release was blocked by staurosporine and K252a and reduced by calphostin C, sphingosine, TMB-8 and W-7 but not affected by H-7, polymyxin B or retinal. It was enhanced by Ro 31-7549. In contrast, leukocyte histamine release induced by calcium ionophore A23187 or by ionomycin was blocked by retinal, TMB-8 and W-7 and reduced by calphostin C and palmitoyl carnitine but enhanced by H-7, staurosporine and polymyxin B; K252a and Ro 31-7549 did not affect such responses. Formyl-methionyl-leucyl-phenylalanine-triggered histamine release was barely affected by any agent used. Thus, the specific PKC inhibitor Ro 31-7549 selectively blocked 4 beta-phorbol 12-myristate 13-acetate-triggered leukocyte histamine release. These results imply that examined secretagogues trigger human leukocyte histamine release through partly separate pathways

  13. Fentanyl enhances the excitability of rapidly adapting receptors to cause cough via the enhancement of histamine release in the airways

    Kamei, Junzo; Nakanishi, Yuki; ASATO, MEGUMI; Ikeda, Hiroko


    Background Although the mechanism of fentanyl-induced cough is unclear, several lines of evidence suggest that allergic mediators, such as histamine, may play a role in the production of fentanyl-induced coughs. The aim of this study was to explore the effects of fentanyl on cough sensitivity to inhaled citric acid and on histamine release in BALF in mice. Methods The cough reflex was induced by the inhalation of citric acid. Male ICR mice were exposed to a nebulized solution of citric acid a...

  14. Basophil histamine release in patients with birch pollen hypersensitivity with and without allergic symptoms to fruits.

    Kleine-Tebbe, J; Galleani, M; Jeep, S; Pilz, B; Baisch, A; Kunkel, G


    Histamine release (HR) studies were performed in 40 birch pollen-allergic patients (positive case history, positive SPT, positive birch pollen-specific serum IgE: RAST > or = 3) with (n = 20, A) and without (n = 20, B) fruit hypersensitivity, and 10 nonatopic volunteers (C). Several fruit allergens were used and characterized by protein determination and immunoblot techniques. Dose-dependent HR (apple peel = apple pulp > peach = cherry) was demonstrated in both allergic groups, but to a higher extent in patients with fruit allergy (P < 0.01). Increased basophil sensitivity to birch pollen was found in the group with fruit allergy (P < 0.001). Strong correlations between the mediator response induced by several fruits indicate common allergens within the extracts. We conclude that fruit-related symptoms require not only high specific serum IgE, but a strong cellular sensitization to birch pollen allergens together with an increased cellular reactivity to fruit allergens. PMID:1283657

  15. Influence of MRI contrast media on histamine release from mast cells

    Mast cells, owing to diversity of secreted mediators, play a crucial role in the regulation of inflammatory response. Together with basophils, mast cells constitute a central pathogenetic element of anaphylactic (IgE-dependent) and anaphylactoid (IgE-independent) reactions. In severe cases, generalized degranulation of mast cells may cause symptoms of anaphylactic shock. The influence of the classical, iodine-based contrast media on mastocyte degranulation has been fully described. Our objective was to determine the influence of the gadolinium-based MRI contrast media on histamine release from mast cells and to compare the activity of ionic and non-ionic preparations of contrast media. To determine the intensity of mast cell degranulation, we used an experimental model based on mastocytes isolated from rat peritoneal fluid. Purified suspensions of mast cells were incubated with various concentrations of Gd-DTPA and Gd-DTPA-BMA, and solutions of PEG 600 which served as a non-toxic osmotic stimulus. The intensity of mast cell activation was presented as mean percentage of histamine released from cells after incubation. The obtained results demonstrate that both ionic and non-ionic preparations of the MRI contrast media are able to induce mast cell degranulation in vitro. It was also proved that the non-ionic MRI contrast media stimulate mast cells markedly more weakly than ionic contrast media at identical concentration. The aforementioned results may suggest a more profitable safety profile of the non-ionic contrast preparations. We may also conclude that triggering of mast cell degranulation after incubation with the solutions of MRI contrast media results from non-specific osmotic stimulation and direct toxicity of free ionic residues

  16. Mobilization of leucocytes and subsequent release of histamine and lysosomal enzymes into the peritoneal and pleural cavities of rats by actinomycin D (dactinomycin).

    Giro, S N; Joshi, B; Peoples, S A


    1. The effects of intraperitoneal injections of actinomycin D on the temporal characteristics of the accumulation of the inflammatory exudate and cells into the peritoneal and pleural cavities were studied in male Sprague Dawley rats. 2. A measurable quantity of the exudate appeared in both cavities within 24 h and reached maxima in the peritoneal and pleural cavities on the fourth and third days, respectively. Thereafter, the accumulated volume of liquid decreased progressively in the peritoneal cavity but stayed more or less at about the same level in the pleural cavity until the sixth day. 3. The pooled peritoneal and pleural exudates contained neutrophils, macrophages, mast cell and eosinophils. The leucocyte infiltration occurred in two phases, the maximum cell numbers being found on the third and fifth days. A precipitous fall in the number of leucocytes occurred on the fourth day. Neutrophils and macrophages accounted for 85-95% of the total number of leucocytes. 4. The supernatant of the inflammatory exudate after centrifugation at 3,000 g contained histamine and the soluble lysosomal enzyme proteins, acid phosphatase and beta-glucuronidase until the sixth day following the initial dose of actinomycin D. 5. It is suggested that the release of lysosomal enzymes in the exudate, subsequent to leucocyte mobilization and the release of histamine from the mast cells, are probably involved in the genesis of inflammatory conditions induced by actinomycin D. PMID:50158

  17. Bradykinin induced wheal and flare is not mediated by histamine release or cyclooxygenase products.

    Crossman, D C; Fuller, R W


    The wheal and flare response to intradermal bradykinin was studied in man. The possibility that histamine and cyclooxygenase products are involved in the response to bradykinin was examined. Terfenadine given by mouth significantly inhibited the cutaneous response to histamine but the effect of bradykinin was unaltered. Similarly the cutaneous response to bradykinin was unchanged by aspirin.

  18. The Effects of Electrical Stimuli on Calcium Change and Histamine Release in Rat Basophilic Leukemia Mast Cells

    Zhu, Dan; Wu, Zu-Hui; Chen, Ji-Yao; Zhou, Lu-Wei


    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. Histamine receptors coupled to [3H]cAMP accumulation in brain: pharmacological characterization in a vesicular preparation of guinea pig cortex

    The histamine-stimulated accumulation of [3H]cAMP (formed by prelabeling with [3H]adenine) was characterized pharmacologically in a vesicular preparation of guinea pig cortex. The H2 antagonist cimetidine maximally blocked 80% of the response, whereas only 45% of the response could be inhibited by H1 antagonists. A combination of H1 and H2 antagonists completely abolished the response. These and other findings show that both H1 and H2 receptors mediate the response, but 25% of the response may require simultaneous activation of both receptors. A role for adenosine as a mediator of the histamine response was investigated. Adenosine deaminase (EC, 2.5 units/ml) decreased basal [3H]cAMP levels, abolished the cimetidine-resistant component of the histamine response, and reduced maximal H1 antagonism of the histamine response to 30%. Treatment with a combination of adenosine deaminase and the calcium chelator EGTA (2 mM) appeared to eliminate the H1 component completely. Under these latter conditions only H2 receptors appeared to mediate the histamine response. Thus, both H1 and H2 receptors stimulate [3H]cAMP accumulation in the vesicular preparation, but the H1 response seems to require either concomitant adenosine or H2 receptor stimulation and may be calcium dependent. These findings differ from those found in broken cell membrane preparations, where only H2 receptors appear to be coupled to adenylate cyclase activation

  20. Effects of H1-receptor antagonists on 14C-aminopyrine accumulated in histamine-stimulated rabbit gastric glands

    After stimulation of gastric acid production there is a considerable delay before the acid starts to appear in the gastric lumen. The present study was carried out on isolated gastric glands to test the hypothesis that there may be a mechanisms in the parietal cell that contributes to this delay by preventing emptying of the secretory canaliculi. Glands were incubated with 14C-aminopyrine and stimulated with histamine. After accumulation of 14C-aminopyrine, various concentration of H1-receptor antagonists were added. Clemastine, promethazine, and hydroxyzine effectively and cetirizine and tripelennamine less effectively decreased the accumulated 14C-aminopyrine content in a dose-dependent manner without significantly reducing the oxygen consumption. The H1-receptor antagonists influenced the 14C-aminopyrine content in another manner than H2-receptor antagonists. No effects were obtained by atropine or lidocaine, indicating that the elimination of 14C-amionopyrine is not an inticholinergic effect or due to membrane effects as exerted by local anesthetics. Stimulation of glands by further addition of histamine did not significantly stimulate the uptake of 14C-aminopyrine in the glands, whereas stimulation with db-cAMP produced an increase that was most pronounced when low concentrations of hydroxyzine had been used. It is suggested that H1-receptor antagonists do not inhibit stimulation of acid production in the secretory canaliculi. They may, however, interfere with a mechanism preventing acid from leaving the parietal cell. Such a mechanism may contribute to the delay in appearance of acid in the gastric lumen after stimulation of gastric acid production. 37 refs., 7 figs

  1. Histamine H4 Receptor mediates interleukin-8 and TNF-α release in human mast cells via multiple signaling pathways.

    Chen, X-F; Zhang, Z; Dou, X; Li, J-J; Zhang, W; Yu, Y-Y; Yu, B; Yu, B


    Histamine, mainly produced by mast cells, is an important inflammatory mediator in immune response. Recently Histamine H4 Receptor (H4R) was also identified in mast cells, from which pro-inflammatory cytokines and chemokines are released. However, the mechanism of how H4R mediates these cytokines and chemokines release in mast cells was still unclear. To further explore the role of H4R in the immune inflammatory response in mast cells, we tested the release of inflammatory cytokine tumor necrosis factor-α (TNF-α), chemokine interleukin-8 (IL-8) and the relevant signaling pathways activated by H4R on LAD2 cells (a human mast cell line). We found that the release of IL-8 and TNF-α were blocked by inhibitors of PI3K, ERK and Ca2+-Calcineurin-NFAT signaling pathways, while the release of these cytokines and chemokines were enhanced by the inhibitor of P38 signaling pathway. However, inhibitors of the JNK and NF-κB signaling pathways had little effect on the expression of the pro-inflammatory mediators. Moreover, activation of the H4R could induce phosphorylation of ERK, p38 and AKT in mast cells. In conclusion, we found that H4R mediates the release of inflammatory cytokine TNF-α and chemokine IL-8 in human mast cells via PI3K, Ca2+-Calcineurin-NFAT and MAPKs signaling pathways. PMID:26828993

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

    Holck, Peter; Sletmoen, Marit; Stokke, Bjørn Torger; Permin, Henrik; Norn, Svend


    (1-->3)-beta-D-Glucans, a cell wall component in most microfungi, are suggested to play a role in the development of respiratory and general symptoms in organic dust-related diseases. The mechanisms by which they induce these effects are, however, not clear. In the present study, mediator release......-D-glucan aggravates IgE-mediated histamine release. Knowledge concerning the effects of glucans on immune responses may be of importance for understanding and treating inflammatory and allergic diseases.......(1-->3)-beta-D-Glucans, a cell wall component in most microfungi, are suggested to play a role in the development of respiratory and general symptoms in organic dust-related diseases. The mechanisms by which they induce these effects are, however, not clear. In the present study, mediator release......,6-branchings: 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...

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

    Jensen, Bettina Margrethe; Assing, K; Jensen, Lone Hummelshøj; Glue, C; Skov, P S; Poulsen, L K


    . 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.......Immunoglobulin (Ig)E-sensitized persons with positive skin prick test, but no allergy symptoms, are classified as being asymptomatic skin sensitized (AS). The allergic type 1 disease is dependant on IgE binding to the high affinity IgE-receptor (FcepsilonRI) expressed on basophils and mast cells...

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

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


    . 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...

  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

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


    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]arachidonic a...

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


    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.

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

    Philip Lazarovici


    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.

  8. Inhibition of anaphylactic histamine release from heterologously sensitized mast cells: differential effects of drugs which interfere with calcium influx.



    Full Text Available Drug effects were studied on anaphylactic histamine release from rat mast cells sensitized in vitro with mouse IgE antibody. When histamine release was elicited by adding Ca-++ at various times after antigen-stimulation of sensitized cells in Ca++-free medium, the drugs to be tested were added shortly before each Ca++ addition. Quercetin was effective only when added before or immediately after antigen. Theophylline and disodium cromoglycate (DSCG were active irrespective of the time interval between antigen and Ca++ addition. Verapamil was more effective when added before or simultaneously with antigen than when added later. When tested in the two-stage experiments, quercetin showed inhibition only in Stage 1 and verapamil was inhibitive primarily in Stage 1, while theophylline and DSCG wee only inhibitive in Stage 2. It seems that quercetin selectively and verapamil primarily act to block calcium-gate opening resulting from antigen-antibody interaction on the mast cell membrane, while theophylline and DSCG selectively inhibit the passage of calcium through open calcium channels.

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

    Kazibwe Francis


    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

  10. Histamine and the striatum.

    Bolam, J Paul; Ellender, Tommas J


    The neuromodulator histamine is released throughout the brain during periods of wakefulness. Combined with an abundant expression of histamine receptors, this suggests potential widespread histaminergic control of neural circuit activity. However, the effect of histamine on many of these circuits is unknown. In this review we will discuss recent evidence for histaminergic modulation of the basal ganglia circuitry, and specifically its main input nucleus; the striatum. Furthermore, we will discuss recent findings of histaminergic dysfunction in several basal ganglia disorders, including in Parkinson's disease and most prominently, in Tourette's syndrome, which has led to a resurgence of interest in this neuromodulator. Combined, these recent observations not only suggest a central role for histamine in modulating basal ganglia activity and behaviour, but also as a possible target in treating basal ganglia disorders. This article is part of the Special Issue entitled 'Histamine Receptors'. PMID:26275849

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

    Guldager, H; Søndergaard, I


    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...

  12. Effects of histamine on the guinea-pig stomach: excitation of smooth muscle and inhibition of transmitter release.

    Ono, H.; Suzuki, H.


    1 The effects of histamine on electrical responses of smooth muscle cells of the guinea-pig stomach were studied. 2 In the fundus, histamine (above 10(-6) M) depolarized the membrane and decreased the membrane resistance. In the antrum, the slow waves were enhanced by histamine, without change in the resting membrane potential or membrane resistance (10(-7)-10(-6) M), or with depolarization of the membrane (above 10(-5) M). 3 When the effects of histamine on neuromuscular transmission were es...

  13. MCP-1-Induced Histamine Release from Mast Cells Is Associated with Development of Interstitial Cystitis/Bladder Pain Syndrome in Rat Models

    Jianwei Lv


    Full Text Available Objective. Interstitial cystitis/bladder pain syndrome (IC/BPS is characterized by overexpression of monocyte chemoattractant protein-1 (MCP-1 in bladder tissues and induction of mast cell (MC degranulation. This study was undertaken to explore the mechanism of action of MCP-1 in the development of IC/BPS. Methods. A rat model of IC/BPS was developed by perfusing bladders of nine SPF- grade female Sprague-Dawley rats with protamine sulfate and lipopolysaccharide (PS+LPS. MCP-1 and histamine levels in bladder tissue and urine were detected by immunohistochemistry and ELISA. MC degranulation was measured by immunofluorescence techniques and chemokine (C-C motif receptor 2 (CCR2 was assayed by flow cytometry. Results. Increased MCP-1 expression in bladder tissue and elevated MCP-1 and histamine levels were observed in the urine of LS+LPS-treated rats. This was accompanied by the expression of CCR2 on MC surfaces, suggesting MCP-1 may induce MC degranulation through CCR2. Exposure to LPS stimulated MCP-1 expression in bladder epithelial cells, and exposure to MCP-1 induced histamine release from MCs. Conclusions. MCP-1 upregulation in IC/BPS is one of possible contributing factors inducing histamine release from MCs. CCR2 is involved in the process of mast cell degranulation in bladder tissues. These changes may contribute to the development of symptoms of IC/BPS.

  14. Histamine release from rodent and human mast cells induced by protoporphyrin and ultraviolet light: studies of the mechanism of mast-cell activation in erythropoietic protoporphyria

    We report that protoporphyrin (PP) and ultraviolet light (UVA) induces histamine release from rat peritoneal mast cells, mouse bone marrow mast cells and human cutaneous mast cells in a dose- and temperature-dependent manner. The mast-cell activation was associated with loss of membrane integrity and inhibited by the hydrogen peroxide scavenger, catalase. Histamine release was independent of extracellular calcium in the rodent mast cells, but was markedly reduced in the absence of calcium in human cells. These findings indicate that PP and UVA induce mast-cell-mediator release by a process that may involve hydrogen peroxide formation. There appear to be differences in response to PP and UVA between rodent and human mast cells. (author)

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

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


    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. PMID:18938170

  16. The role of histamine in neurogenic inflammation

    Rosa, A. C.; Fantozzi, R


    The term ‘neurogenic inflammation’ has been adopted to describe the local release of inflammatory mediators, such as substance P and calcitonin gene-related peptide, from neurons. Once released, these neuropeptides induce the release of histamine from adjacent mast cells. In turn, histamine evokes the release of substance P and calcitonin gene-related peptide; thus, a bidirectional link between histamine and neuropeptides in neurogenic inflammation is established. The aim of this review is to...

  17. Mosla dianthera inhibits mast cell-mediated allergic reactions through the inhibition of histamine release and inflammatory cytokine production

    In this study, we investigated the effect of the aqueous extract of Mosla dianthera (Maxim.) (AEMD) on the mast cell-mediated allergy model and studied the possible mechanism of action. Mast cell-mediated allergic disease is involved in many diseases such as asthma, sinusitis and rheumatoid arthritis. The discovery of drugs for the treatment of allergic disease is an important subject in human health. AEMD inhibited compound 48/80-induced systemic reactions in mice. AEMD decreased immunoglobulin E-mediated local allergic reactions, passive cutaneous anaphylaxis. AEMD attenuated intracellular calcium level and release of histamine from rat peritoneal mast cells activated by compound 48/80. Furthermore, AEMD attenuated the phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187-stimulated TNF-α, IL-8 and IL-6 secretion in human mast cells. The inhibitory effect of AEMD on the pro-inflammatory cytokines was nuclear factor-κB (NF-κB) dependent. AEMD decreased PMA and A23187-induced degradation of IκBα and nuclear translocation of NF-κB. Our findings provide evidence that AEMD inhibits mast cell-derived immediate-type allergic reactions and involvement of pro-inflammatory cytokines and NF-κB in these effects

  18. Effect of progesterone on the release of arachidonic acid from human endometrial cells stimulated by histamine

    Progesterone at concentrations of 10(-7)M and 10(-8)M inhibits release of [3H]-arachidonic acid from stimulated, perfused, endometrial cells. The effect is independent of the mechanism of stimulation. Cortisol (10(-5)M but not 10(-7)M) has a similar effect in this system but estradiol (10(-7)M) is without effect. There was a positive correlation (p less than 0.05) between the magnitude of inhibition by progesterone and the day of cycle. The inhibitory action of progesterone on the release of arachidonic acid was greater in endometrial cells than in decidual cells and was apparent after fifteen minutes. The activities of commercial and endometrial cell-free preparations of phospholipase A2 and phospholipase C were unaffected by the presence of progesterone. We conclude that progesterone modulates release of [3H]-arachidonic acid from endometrial cells by a rapid, indirect action on phospholipase activity

  19. The Effect of Ouabain on Histamine Release from Human Skin Mast Cells

    Şenol, Mustafa; Özerol, İ. Halil; Patel, Asha V.; Skoner, David P.


    There are controversial reports on the effect of sodium-potassium adenosine triphosphatase (Na+-K+ ATPase) inhibition on mast cell mediator release. Some of them have indicated that ouabain (strophanthin G), a specific Na+-K+ ATPase inhibitor, inhibited the release, whereas the others have shown that ouabain had no effect or even had a stimulatory effect on the mediator secretion. Most of these studies utilized animal-derived cells. The aim of this study was to determine the effect of Na+-K+ ...

  20. Histamine modulates nitric oxide release by microglia and dopaminergic neuronal survival

    Pires, Joel Pereira


    Microglia cells, the resident immune cells in the brain, play a critical role in the development and progression of several neurodegenerative diseases. Parkinson's disease (PD) is a neurodegenerative disorder characterized by a dramatic loss of dopaminergic neurons (DA) in the substantia nigra (SN), striatal dopamine depletion and motor impairments. Accumulating clinical and experimental evidences suggest that neuroinflammation plays a critical role in the pathogenesis of PD through the activ...

  1. Aldehyde dehydrogenase type 2 activation by adenosine and histamine inhibits ischemic norepinephrine release in cardiac sympathetic neurons: mediation by protein kinase Cε.

    Robador, Pablo A; Seyedi, Nahid; Chan, Noel Yan-Ki; Koda, Kenichiro; Levi, Roberto


    During myocardial ischemia/reperfusion, lipid peroxidation leads to the formation of toxic aldehydes that contribute to ischemic dysfunction. Mitochondrial aldehyde dehydrogenase type 2 (ALDH2) alleviates ischemic heart damage and reperfusion arrhythmias via aldehyde detoxification. Because excessive norepinephrine release in the heart is a pivotal arrhythmogenic mechanism, we hypothesized that neuronal ALDH2 activation might diminish ischemic norepinephrine release. Incubation of cardiac sympathetic nerve endings with acetaldehyde, at concentrations achieved in myocardial ischemia, caused a concentration-dependent increase in norepinephrine release. A major increase in norepinephrine release also occurred when sympathetic nerve endings were incubated in hypoxic conditions. ALDH2 activation substantially reduced acetaldehyde- and hypoxia-induced norepinephrine release, an action prevented by inhibition of ALDH2 or protein kinase Cε (PKCε). Selective activation of G(i/o)-coupled adenosine A(1), A(3), or histamine H(3) receptors markedly inhibited both acetaldehyde- and hypoxia-induced norepinephrine release. These effects were also abolished by PKCε and/or ALDH2 inhibition. Moreover, A(1)-, A(3)-, or H(3)-receptor activation increased ALDH2 activity in a sympathetic neuron model (differentiated PC12 cells stably transfected with H(3) receptors). This action was prevented by the inhibition of PKCε and ALDH2. Our findings suggest the existence in sympathetic neurons of a protective pathway initiated by A(1)-, A(3)-, and H(3)-receptor activation by adenosine and histamine released in close proximity of these terminals. This pathway comprises the sequential activation of PKCε and ALDH2, culminating in aldehyde detoxification and inhibition of hypoxic norepinephrine release. Thus, pharmacological activation of PKCε and ALDH2 in cardiac sympathetic nerves may have significant protective effects by alleviating norepinephrine-induced life-threatening arrhythmias that

  2. Histamine H4-receptors inhibit mast cell renin release in ischemia/reperfusion via protein kinase C ε-dependent aldehyde dehydrogenase type-2 activation.

    Aldi, Silvia; Takano, Ken-ichi; Tomita, Kengo; Koda, Kenichiro; Chan, Noel Y-K; Marino, Alice; Salazar-Rodriguez, Mariselis; Thurmond, Robin L; Levi, Roberto


    Renin released by ischemia/reperfusion (I/R) from cardiac mast cells (MCs) activates a local renin-angiotensin system (RAS) causing arrhythmic dysfunction. Ischemic preconditioning (IPC) inhibits MC renin release and consequent activation of this local RAS. We postulated that MC histamine H4-receptors (H4Rs), being Gαi/o-coupled, might activate a protein kinase C isotype-ε (PKCε)-aldehyde dehydrogenase type-2 (ALDH2) cascade, ultimately eliminating MC-degranulating and renin-releasing effects of aldehydes formed in I/R and associated arrhythmias. We tested this hypothesis in ex vivo hearts, human mastocytoma cells, and bone marrow-derived MCs from wild-type and H4R knockout mice. We found that activation of MC H4Rs mimics the cardioprotective anti-RAS effects of IPC and that protection depends on the sequential activation of PKCε and ALDH2 in MCs, reducing aldehyde-induced MC degranulation and renin release and alleviating reperfusion arrhythmias. These cardioprotective effects are mimicked by selective H4R agonists and disappear when H4Rs are pharmacologically blocked or genetically deleted. Our results uncover a novel cardioprotective pathway in I/R, whereby activation of H4Rs on the MC membrane, possibly by MC-derived histamine, leads sequentially to PKCε and ALDH2 activation, reduction of toxic aldehyde-induced MC renin release, prevention of RAS activation, reduction of norepinephrine release, and ultimately to alleviation of reperfusion arrhythmias. This newly discovered protective pathway suggests that MC H4Rs may represent a new pharmacologic and therapeutic target for the direct alleviation of RAS-induced cardiac dysfunctions, including ischemic heart disease and congestive heart failure. PMID:24696042

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

    Muhammad Nazrul Hakim


    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.

  4. Interleukin-4 (IL-4 enhances and soluble interleukin-4 receptor (sIL-4R inhibits histamine release from peripheral blood basophils and mast cells in vitro and in vivo

    B. Niggemann


    Full Text Available The aim of the study was to analyse the effect of interleukin-4 (IL-4 on allergen and anti-IgE mediated histamine release from basophils and human skin mast cells and to assess whether soluble recombinant interleukin-4 receptor (sIL4R can inhibit these effects. Anti-IgE stimulated histamine release from peripheral blood basophils and mast cells of atopic donors was enhanced after preincubation with IL-4, whereas after preincubation with sIL-4R it was inhibited. These effects were even more pronounced when samples were stimulated with a clinically relevant allergen. In IL-4 preincubated skin mast cells, there was a similar enhancement of anti-IgE stimulated histamine release, which could again be inhibited by sIL-4R. The effects of IL-4 and sIL4R were dose- and time-dependent. Mice sensitized to ovalbumin and treated with soluble recombinant murine sIL-4R showed significantly reduced immediate-type cutaneous hypersensitivity responses compared with untreated mice. These in vivo effects were IgE independent, since there were no significant differences in total and allergen specific IgE/IgG1 antibody titres between treated and untreated mice. This indicates that IL4 exerts priming effects on histamine release by effector cells of the allergic response and that these effects are potently antagonized by soluble IL-4R both in vitro and in vivo.

  5. Autoregulation of enterochromaffin-like cell histamine secretion via the histamine 3 receptor subtype.

    Kidd, M.; Tang, L. H.; Miu, K.; Lawton, G. P.; Sandor, A.; Modlin, I. M.


    INTRODUCTION: The neuroendocrine histamine-secreting cell of the gastric fundus, the enferochromaffin-like cell, is the principal regulator of parietal cell acid secretion. We have proposed that histamine may regulate its own synthesis and release via an autocrine mechanism. The purpose of this study was to evaluate the role of the histamine receptor subtypes H1, H2 and H3 in the regulation of this phenomenon. METHODS: Purified ECL cells were isolated by pronase digestion and EDTA exposure of...

  6. Gastrointestinal histamine and histamine formation capacity after gastric irradiation in mice

    Mice were exposed to a single dose of 9 or 15 Gy of X rays directed to the stomach. After 9 Gy, mean gastric mural histamine fell to 61% of the control value 7 days after irradiation while HFC rose to 172%. Histamine and HFC returned to control values within 2 weeks of irradiation. With 15 Gy, on Day 7, histamine fell to 46%, HFC rose to 260%. Histamine concentration remained low (less than half control value) while HFC returned to normal. These dose-dependent changes in histamine were observed neither elsewhere in the gut nor in circulating blood. Further groups were exposed to 3, 6, 9 or 15 Gy to the stomach, with gastric histamine and HFC assayed on Day 7. Histamine concentration was inversely related to dose and HFC was directly dose dependent. These results suggest that irradiation of the stomach may reduce gastric histamine without inducing a general histamine release. Depletion of the gastric histamine store may explain the inhibitory effect of irradiation of the stomach on gastric acid secretion. (author)

  7. Histamine modulates contraction and cyclic nucleotides in cultured rat mesangial cells. Differential effects mediated by histamine H1 and H2 receptors.

    Sedor, J R; Abboud, H. E.


    Histamine influences the glomerular microcirculation and modulates immune-inflammatory responses. In the rat kidney, histamine is synthesized by glomeruli and stimulates cyclic nucleotide production specifically in glomeruli. We investigated the in vitro effect of histamine on cyclic nucleotide accumulation in rat cultured glomerular mesangial and epithelial cells. Histamine stimulated cyclic AMP (cAMP) accumulation in cultured mesangial cells (64.0 +/- 22.1 to 511.4 +/- 86.6 pmol/mg protein,...

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

    The release of [3H]GABA from slices of rat substantia nigra pars reticulata induced by increasing extracellular K+ from 6 to 15 mM in the presence of 10 μM sulpiride was inhibited by 73±3% by 1 μM SCH 23390, consistent with a large component of release dependent upon D1 receptor activation. The histamine H3 receptor-selective agonist immepip (1 μM) and the non-selective agonist histamine (100 μM) inhibited [3H]GABA release by 78±2 and 80±2%, respectively. The inhibition by both agonists was reversed by the H3 receptor antagonist thioperamide (1 μM). However, in the presence of 1 μM SCH 23390 depolarization-induced release of [3H]GABA was not significantly decreased by 1 μM immepip. In rats depleted of dopamine by pretreatment with reserpine, immepip no longer inhibited control release of [3H]GABA, but in the presence of 1 μM SKF 38393, which produced a 7±1-fold stimulation of release, immepip reduced the release to a level not statistically different from that in the presence of immepip alone. Immepip (1 μM) also inhibited the depolarization-induced release of [3H]dopamine from substantia nigra pars reticulata slices, by 38±3%.The evidence is consistent with the proposition that activation of histamine H3 receptors leads to the selective inhibition of the component of depolarization-induced [3H]GABA release in substantia nigra pars reticulata slices which is dependent upon D1 receptor activation. This appears to be largely an action at the terminals of the striatonigral GABA projection neurons, which may be enhanced by a partial inhibition of dendritic [3H]dopamine release. (Copyright (c) 1997 Elsevier Science B.V., Amsterdam. All rights reserved.)

  9. LRRK2 Promotes Tau Accumulation, Aggregation and Release.

    Guerreiro, Patrícia Silva; Gerhardt, Ellen; Lopes da Fonseca, Tomás; Bähr, Mathias; Outeiro, Tiago Fleming; Eckermann, Katrin


    Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are known as the most frequent cause of familial Parkinson's disease (PD), but are also present in sporadic cases. The G2019S-LRRK2 mutation is located in the kinase domain of the protein, and has consistently been reported to promote a gain of kinase function. Several proteins have been reported as LRRK2 substrates and/or interactors, suggesting possible pathways involved in neurodegeneration in PD. Hyperphosphorylated Tau protein accumulates in neurofibrillary tangles, a typical pathological hallmark in Alzheimer's disease and frontotemporal dementia. In addition, it is also frequently found in the brains of PD patients. Although LRRK2 is a kinase, it appears that a putative interaction with Tau is phosphorylation-independent. However, the underlying mechanisms and the cellular consequences of this interaction are still unclear. In this study, we demonstrate an interaction between LRRK2 and Tau and that LRRK2 promotes the accumulation of non-monomeric and high-molecular weight (HMW) Tau species independent of its kinase activity. Interestingly, we found that LRRK2 increases Tau secretion, possibly as a consequence of an impairment of Tau proteasomal degradation. Our data highlight a mechanism through which LRRK2 regulates intracellular Tau levels, contributing to the progression of the pathology caused by the LRRK2-mediated proteasome impairment. In total, our findings suggest that the interplay between LRRK2 and proteasome activity might constitute a valid target for therapeutic intervention in PD. PMID:26014385

  10. Histamine in regulation of bone remodeling processes

    Marek Wiercigroch


    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.

  11. [Histamine in regulation of bone remodeling processes].

    Wiercigroch, Marek; Folwarczna, Joanna


    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. PMID:24018454

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

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


    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.......90 and 0.10, respectively. The SCT with the same extracts showed sensitivities of 0.30, 0.50 and 0.20, respectively. The sensitivity of specific IgE to apple were 0.90 (CAP) and 0.10 (ML). The sensitivity of the HR test was 90% (A72), and 25% using the commercial extract. CONCLUSION: The SPT and HR test...

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

    Nielsen, Hans Jørgen


    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......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...... 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...

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

    Nielsen, Hans Jørgen


    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......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...

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

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


    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. PMID:23814966

  16. Experimental study of spontaneous release of accumulated energy in irradiated ices

    Shabalin, E.; Kulagin, E.; Kulikov, S.; Melikhov, V.


    A phenomenon of spontaneous release of energy accumulated in some hydrogenous materials under fast neutron irradiation at low temperature was studied at a cryogenic irradiation facility of the IBR-2 reactor in Dubna for the purpose of cold neutron moderator development. Spontaneous release of energy occurred in water ice after 5-11 h of fast neutron irradiation at temperature burp was observed in solid methane.

  17. Intracellular accumulation of indium ions released from nanoparticles induces oxidative stress, proinflammatory response and DNA damage.

    Tabei, Yosuke; Sonoda, Akinari; Nakajima, Yoshihiro; Biju, Vasudevanpillai; Makita, Yoji; Yoshida, Yasukazu; Horie, Masanori


    Due to the widespread use of indium tin oxide (ITO), it is important to investigate its effect on human health. In this study, we evaluated the cellular effects of ITO nanoparticles (NPs), indium chloride (InCl3) and tin chloride (SnCl3) using human lung epithelial A549 cells. Transmission electron microscopy and inductively coupled plasma mass spectrometry were employed to study cellular ITO NP uptake. Interestingly, greater uptake of ITO NPs was observed, as compared with soluble salts. ITO NP species released could be divided into two types: 'indium release ITO' or 'tin release ITO'. We incubated A549 cells with indium release ITO, tin release ITO, InCl3 or SnCl2 and investigated oxidative stress, proinflammatory response, cytotoxicity and DNA damage. We found that intracellular reactive oxygen species were increased in cells incubated with indium release ITO, but not tin release ITO, InCl3 or SnCl2. Messenger RNA and protein levels of the inflammatory marker, interleukin-8, also increased following exposure to indium release ITO. Furthermore, the alkaline comet assay revealed that intracellular accumulation of indium ions induced DNA damage. Our results demonstrate that the accumulation of ionic indium, but not ionic tin, from ITO NPs in the intracellular matrix has extensive cellular effects. PMID:26378248

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

    Nielsen, Hans Jørgen


    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......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...

  19. The inhibition of substance P-induced histamine release from mast cells by 6, 7-dihydro-6, 8, 8, 10-tetramethyl-8H-pyrano-[3, 2-g] chromone-2-carboxylic acid (EAA).

    Tsutsumi, Koji; Nishibori, Masahiro; Saeki, Kiyomi


    In the presence of extracellular Ca2+, 6,7-dihydro-6,8,8, 10-tetramethyl-8H-pyrano [3, 2-g] chromone-2-carboxylic acid (EAA) had an inhibitory effect on the substance P-induced histamine release from rat peritoneal mast cells. Not only Ca2+ but also Mg2+, Sr2+ and Ba2+ were effective in enhancing the activity of EAA. Marked tachyphylaxis to EAA developed irrespective of the presence or absence of extracellular Ca2+. Cross-tachyphylaxis was observed between EAA and disodium cromoglycate (DSCG)...

  20. Vascular Effects of Histamine.

    Ebeigbe, Anthony B; Talabi, Olufunke O


    Four subtypes of receptors (H1, H2, H3 and H4) mediate the actions of histamine. In the vascular wall, the effects of histamine are mediated via H1 and H2 receptors and the actions are modulated by H3 receptor subtype located on presynaptic neurones. Alterations in vascular responses to histamine are associated with experimental as well as a human form of hypertension, suggesting a role for histanine in cardiovascular regulation. PMID:26196559

  1. The new biology of histamine receptors.

    Huang, Jing-Feng; Thurmond, Robin L


    The physiologic functions of histamine have been recognized for more than 100 years, yet new roles are still being uncovered. Most importantly, a newly discovered receptor of the amine has helped refine our understanding of histamine. This new receptor, the histamine H4 receptor (H4R), has a higher affinity for histamine compared with the histamine H1 receptor and appears to be more selectively expressed, found mainly on hematopoietic cells. H4R is involved in chemotaxis and inflammatory mediator release by eosinophils, mast cells, monocytes, dendritic cells, and T cells. Studies in animal models using selective antagonists or H4R-deficient mice have shown a role for the receptor in inflammation in vivo. In particular, H4R antagonists have shown promise in experimental models of asthma and pruritus, two conditions where currently marketed antihistamines targeting the histamine H1 receptor are not optimally effective in humans. Thus, a new class of H4R-specific antihistamines may be distinctively effective in treating allergic diseases associated with chronic pruritus and asthma. PMID:18377770

  2. Experimental study of spontaneous release of accumulated energy in irradiated ices

    A phenomenon of spontaneous release of energy accumulated in some hydrogenous materials under fast neutron irradiation at low temperature was studied at a cryogenic irradiation facility of the IBR-2 reactor in Dubna for the purpose of cold neutron moderator development. Spontaneous release of energy occurred in water ice after 5-11 h of fast neutron irradiation at temperature <34 K and at absorbed dose rate 0.4 MGy/h. In contrast with previous data, no spontaneous burp was observed in solid methane

  3. Experimental study of spontaneous release of accumulated energy in irradiated ices

    Shabalin, E.; Kulagin, E.; Kulikov, S. E-mail:; Melikhov, V


    A phenomenon of spontaneous release of energy accumulated in some hydrogenous materials under fast neutron irradiation at low temperature was studied at a cryogenic irradiation facility of the IBR-2 reactor in Dubna for the purpose of cold neutron moderator development. Spontaneous release of energy occurred in water ice after 5-11 h of fast neutron irradiation at temperature <34 K and at absorbed dose rate 0.4 MGy/h. In contrast with previous data, no spontaneous burp was observed in solid methane.

  4. Seismicity research in the subregions of Chinese mainland using strain accumulating and releasing model based on G-R relation

    MA Hong-sheng; LIU Jie; ZHANG Guo-min; ZHANG Xiao-dong; WANG Hui; LI Wen-jun


    According to the deficiency of the strain accumulating and releasing curves and the previous models, the strain-accumulating rate of the strain accumulating and releasing model has been deduced based on the G-R rela tion and the empirical formula between energy release and earthquake magnitude, where the strain-accumulating rate is relative independent of the strain-releasing rate. Five typical areas in Chinese mainland are selected on the basis of the hypothesis on active tectonic block, and small earthquakes from 1970 are imported to calculate the annual strain-accumulating rates considering the completeness of historical seismic data. Having introduced the strain-accumulating rates into the amended model, present strain phases are got. According to the present stages in their own cycles, the future earthquake tendency of each sub-region is discussed.

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

    Fan Yang; Qing Yang; Xingxing Liu; Pan Wang


    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...


    Niraj*, M. M. Gupta and Shweta Pandey


    Full Text Available Some biogenic amine like Histamine, cadaverine and putrescine have been confirmed as useful chemical indicators to estimate bacterial spoilage of foods, particularly fish and fish products, cheese, meat and fermented foods. Histamine is toxic at high intakes, while cadaverine and putrescine potentiate the effects of Histamine. Histamine has regulated level of 200 mg/kg (200 ppm. Basic principle involved in Biogenic amines biosensor is the action of diamine oxidase (DAO that catalyzes the oxidative deamination of primary amines to the corresponding aldehydes, hydrogen peroxide and ammonia. Two different approaches for the histamine biosensor design were studied, i.e. the enzyme DAO was directly immobilized on the surface of the oxygen electrode membrane using glutaraldehyde or entrapped in a hydrogel film. In histamine biosensor consisting of diamine oxidase (DAO and a conventional oxygen electrode transducer was developed and applied for the determination of standard histamine solutions. For immobilisation with glutaraldehyde, the enzyme was cross-linked with glutaraldehyde as a bifunctional reagent on the electrode surface. For entrapment, DAO was entrapped in a polymeric hydrogel film, i.e. poly(hydroxyl ethyl methacrylate (pHEMA polymer and deposited onto the teflon membrane of the oxygen electrode. Good linear correlation response obtained of the histamine biosensors with immobilized DAO showed between the changes of oxygen level with changes in concentration of histamine at both high concentration ranges (200-1000 mg/L and low concentrations (20-100 mg/L. However, the sensitivity of the biosensor response decreased at high concentration range of histamine, for the direct DAO immobilisation with glutaraldehyde. Biogenic amines concentration can be measured by monitoring either the decrease in oxygen or the increase of hydrogen peroxide concentration.

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

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


    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. PMID:25754956

  8. On histamine and appetites

    Fernando eTorrealba


    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.

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

    Fan Yang


    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.

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

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


    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

  11. The inhibition of substance P-induced histamine release from mast cells by 6, 7-dihydro-6, 8, 8, 10-tetramethyl-8H-pyrano-[3, 2-g] chromone-2-carboxylic acid (EAA.



    Full Text Available In the presence of extracellular Ca2+, 6,7-dihydro-6,8,8, 10-tetramethyl-8H-pyrano [3, 2-g] chromone-2-carboxylic acid (EAA had an inhibitory effect on the substance P-induced histamine release from rat peritoneal mast cells. Not only Ca2+ but also Mg2+, Sr2+ and Ba2+ were effective in enhancing the activity of EAA. Marked tachyphylaxis to EAA developed irrespective of the presence or absence of extracellular Ca2+. Cross-tachyphylaxis was observed between EAA and disodium cromoglycate (DSCG. These results indicate that the mode of action of EAA is similar, but not identical, with that of DSCG.

  12. PA01.80. The review of herbal anti-allergy and anti-histaminic drugs

    Kalaskar, Sneha; Nishteswar, K.; ,


    Purpose: The symptoms of an allergic reaction communicate sensitization to certain antigens in the environment. Initiation of antigen reaction stimulates mast cells to release histamine into the blood which interacts with the cells to produce most of the symptoms of the allergy. Drugs that block only the action of histamine are known as antihistaminic while the drugs preventing mast cells from releasing histamine are considered as anti allergic agents. Ayurveda considers Mandagni (Jadharagni ...

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

    Reese, Imke


    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. PMID:27177895

  14. Histamine induces the production of matrix metalloproteinase-9 in human astrocytic cultures via H1-receptor subtype.

    Patel, Aarti; Vasanthan, Vishnu; Fu, Wen; Fahlman, Richard P; MacTavish, David; Jhamandas, Jack H


    Accumulation of β-amyloid (Aβ) protein within the brain is a neuropathological hallmark of Alzheimer's disease (AD). One strategy to facilitate Aβ clearance from the brain is to promote Aβ catabolism. Matrix metalloproteinase-9 (MMP-9), a member of the family of Zn(+2)-containing endoproteases, known to be expressed and secreted by astrocytes, is capable of degrading Aβ. Histamine, a major aminergic brain neurotransmitter, stimulates the production of MMP-9 in keratinocytes through the histamine H1 receptor (H1R). In the present study, we show that histamine evokes a concentration- and calcium-dependent release of MMP-9 from human astrocytic U373 cells and primary cultures of human and rat astrocytes through the H1R subtype. Activation of H1R on astrocytes elevated intracellular levels of Ca(2+) that was accompanied by time-dependent increases in MAP kinase p44/p42 and PKC. In-cell western blots revealed dose-dependent increases in both enzymes, confirming involvement of these signal transduction pathways. We next investigated the extent of recombinant human MMP-9 (rhMMP-9) proteolytic activity on soluble oligomeric Aβ (soAβ). Mass spectrometry demonstrated time-dependent cleavage of soAβ (20 μM), but not another amyloidogenic protein amylin, upon incubation with rhMMP-9 (100 nM) at 1, 4 and 17 h. Furthermore, Western blots showed a shift in soAβ equilibrium toward lower order, less toxic monomeric species. In conclusion, both MAPK p44/p42 and PKC pathways appear to be involved in histamine-upregulated MMP-9 release via H1Rs in astrocytes. Furthermore, MMP-9 appears to cleave soAβ into less toxic monomeric species. Given the key role of histamine in MMP-9 release, this neurotransmitter may serve as a potential therapeutic target for AD. PMID:25682263

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

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


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

  16. Mast cell chymase potentiates histamine-induced wheal formation in the skin of ragweed-allergic dogs.

    Rubinstein, I; Nadel, J A; Graf, P D; Caughey, G H


    Skin mast cells release the neutral protease chymase along with histamine during degranulation. To test the hypothesis that chymase modulates histamine-induced plasma extravasation, we measured wheal formation following intradermal injection of purified mast cell chymase and histamine into the skin of ragweed-allergic dogs. We found that chymase greatly augments histamine-induced wheal formation. The magnitude of the potentiating effect increases with increasing doses of chymase and becomes m...

  17. Volatiles released by endophytic Pseudomonas fluorescens promoting the growth and volatile oil accumulation in Atractylodes lancea.

    Zhou, Jia-Yu; Li, Xia; Zheng, Jiao-Yan; Dai, Chuan-Chao


    Atractylodes lancea is a well-known, but endangered, Chinese medicinal plant whose volatile oils are its main active components. As the volatile oil content in cultivated A. lancea is much lower than that in the wild herb, the application of microbes or related elicitors to promote growth and volatile oil accumulation in the cultivated herb is an important area of research. This study demonstrates that the endophytic bacterium Pseudomonas fluorescens ALEB7B isolated from the geo-authentic A. lancea can release several nitrogenous volatiles, such as formamide and N,N-dimethyl-formamide, which significantly promote the growth of non-infected A. lancea. Moreover, the main bacterial volatile benzaldehyde significantly promotes volatile oil accumulation in non-infected A. lancea via activating plant defense responses. Notably, the bacterial nitrogenous volatiles cannot be detected in the A. lancea - Pseudomonas fluorescens symbiont while the benzaldehyde can be detected, indicating the nitrogenous volatiles or their precursors may have been consumed by the host plant. This study firstly demonstrates that the interaction between plant and endophytic bacterium is not limited to the commonly known physical contact, extending the ecological functions of endophyte in the phytosphere and deepening the understandings about the symbiotic interaction. PMID:26874622

  18. Histamine modulates multiple functional activities of monocyte-derived dendritic cell subsets via histamine receptor 2.

    Simon, Tünde; Gogolák, Péter; Kis-Tóth, Katalin; Jelinek, Ivett; László, Valéria; Rajnavölgyi, Eva


    Expression of CD1a proteins in human monocyte-derived dendritic cells (DCs) specifies functionally distinct subsets with different inflammatory properties. Histamine is recognized as an inflammatory mediator released by various cell types including DCs. The diverse biological effects of histamine are mediated by G-protein-coupled histamine receptors (HRs), which are able to modulate the functional activities of DC subsets. The goal of the present study was to compare the expression and activity of HRs in the CD1a(-) and CD1a(+) monocyte-derived DC subsets and to test the effects of histamine on the differentiation, activation and functional activities of these subsets. We show that H2R is present at high levels in both DC subsets, whereas H1R and H4R are expressed in a subset-specific manner. Histamine shifts DC differentiation to the development of CD1a(-) DCs and modulates DC activation through its inhibitory effect on CD1a(+) DC differentiation. Histamine-induced reduction of CD1a(+) DCs is associated with increased secretion of IL-6 and IL-10, up-regulation of a typical combination of chemokines, expression C5aR1 by the CD1a(-) DC subset and enhanced migration of both activated DC subsets supported by the production of MMP-9 and MMP-12 enzymes. All these effects were shown to be mediated in a H2R-specific manner as revealed by the specific antagonist of the receptor. As H2R is expressed at high levels in both DC subsets, we propose that it may dominate the regulation of multiple DC functions. In contrast, H1R and H4R with opposing subset-related expression may have a regulatory or fine-tuning role in histamine-induced functional activities. PMID:22232416

  19. Occurrence of Histamine Forming Bacteria and Histamine in Dried Fish

    Devarajan Sumitha


    Full Text Available Natural spoilage of protein rich foods leads to the production of histamine, which is associated with histamine poisoning throughout the world. Fish and fish products are at times associated with major concern due to the presence of histamine, which at toxic level generates histamine or scombroid poisoning known to be contaminated with high levels of histamine leading to histamine poisoning. Histamine consumption is also considered to be of health concerns at chronic levels due to effects on the physiological functions. Dried fish are known to be one of the most popular fish products consumed in the Indian subcontinent, often prepared under unhygienic conditions. In this present study, fifteen dried fish sold in local retail markets were purchased and screened to determine the occurrence of histamine and histamine-forming bacteria. The levels of pH, salt, moisture content and Aerobic Plate Count (APC were determined in all samples and ranged from 5.46 to 7.07, 0.5 to 1.19%, 33 to 77.05% and 10.5 to 11.4 log CFU/g respectively. Two strains of Enterobactercancerogenous PUFSTFMDf01 and Enterobacter sp., PUFSTFMDf02 were identified as histamine forming bacteria in dried fish samples. All fifteen dried fish samples contained an average histamine content of 10.03 mg/100 g which is greater than the guideline value (5 mg/100 g suggested by USFDA.

  20. Postischemic regulation of central histamine receptors.

    Lozada, A; Munyao, N; Sallmen, T; Lintunen, M; Leurs, R; Lindsberg, P J; Panula, P


    This study characterizes changes occurring in the central histaminergic system associated with ischemia-reperfusion pathology in the rat. Specifically, after a postocclusion time period of 48 h, we have analyzed histamine H(1) receptor mRNA expression, histamine H(2) receptor protein amount and binding densities, and histamine H(3) receptor mRNA expression and binding densities in brain regions that have been suggested to be selectively vulnerable to transient global ischemia, i.e. hippocampus, thalamus, caudate-putamen, and cerebral cortex. We found an increase in H(1) receptor mRNA expression in the caudate-putamen: given that ischemia reduces glucose uptake and H(1) receptor activation has been shown to decrease this effect, an increase of expression levels may result in mitigating tissue damage due to energy failure observed in ischemia. A decrease in H(2) receptor binding densities in the caudate-putamen was also observed; the ischemia-induced decrease in H(2) receptor protein was also detectable by Western blot analysis. This phenomenon may underlie the previously reported ischemia induced striatal dopamine release. H(3) receptor mRNA expression was increased in the caudate putamen of the postischemic brain but was decreased in the globus pallidus and the thalamus; in association with this, H(3) receptor binding densities were increased in the cortex, caudate-putamen, globus pallidus, and hippocampus. The upregulation of H(3) receptor ligand binding may be involved in the previously reported continuous neuronal histamine release. Our data suggest that central histamine receptor expression and ligand binding are altered in brain ischemia in distinct areas, and may participate in neuroprotection and/or ischemia-associated neuronal damage. PMID:16181737

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

    Shao-Heng He; Hua Xie


    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 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.

  2. H2 receptor blockade and bronchial hyperreactivity to histamine in asthma.

    Nogrady, S G; Bevan, C


    The role of histamine H1 and H2 receptors in the lung is not clear. H1 receptor blockade results in bronchodilatation and inhibition of histamine induced bronchoconstriction. H2 receptor blockade in vitro prevents the normal negative feedback of histamine on further mediator release in antigen challenge. Bronchospasm in guinea pigs given antigen challenge is enhanced by previous administration of metiamide or burimamide but not of cimetidine. These findings suggest the possible deleterious ef...

  3. Histamine and histidine effects on the transport of dopamine in the rat brain synaptosomes

    The effects of histamine (HA) on dopamine (DA) transport in rat brain synaptosomes has been studied. The exogenous HA inhibited the veratridine-evoked DA release, but had no effect on the DA uptake. A drop of DA uptake to synaptosomes under the conditions favoring histamine synthesis from histidine was connected with histidine itself, but not with the formed histamine. (author). 20 refs, 5 figs

  4. Aldehyde Dehydrogenase Type 2 Activation by Adenosine and Histamine Inhibits Ischemic Norepinephrine Release in Cardiac Sympathetic Neurons: Mediation by Protein Kinase Cε

    Robador, Pablo A.; Seyedi, Nahid; Chan, Noel Yan-Ki; Koda, Kenichiro; Levi, Roberto


    During myocardial ischemia/reperfusion, lipid peroxidation leads to the formation of toxic aldehydes that contribute to ischemic dysfunction. Mitochondrial aldehyde dehydrogenase type 2 (ALDH2) alleviates ischemic heart damage and reperfusion arrhythmias via aldehyde detoxification. Because excessive norepinephrine release in the heart is a pivotal arrhythmogenic mechanism, we hypothesized that neuronal ALDH2 activation might diminish ischemic norepinephrine release. Incubation of cardiac sym...

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

    Sandra M Rocha


    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.

  6. Functional Profiling of 2-Aminopyrimidine Histamine H4 Receptor Modulators.

    Tichenor, Mark S; Thurmond, Robin L; Venable, Jennifer D; Savall, Brad M


    Histamine is an important endogenous signaling molecule that is involved in a number of physiological processes including allergic reactions, gastric acid secretion, neurotransmitter release, and inflammation. The biological effects of histamine are mediated by four histamine receptors with distinct functions and distribution profiles (H1-H4). The most recently discovered histamine receptor (H4) has emerged as a promising drug target for treating inflammatory diseases. A detailed understanding of the role of the H4 receptor in human disease remains elusive, in part because low sequence similarity between the human and rodent H4 receptors complicates the translation of preclinical pharmacology to humans. This review provides an overview of H4 drug discovery programs that have studied cross-species structure-activity relationships, with a focus on the functional profiling of the 2-aminopyrimidine chemotype that has advanced to the clinic for allergy, atopic dermatitis, asthma, and rheumatoid arthritis. PMID:25993395

  7. Xanthurenic acid distribution, transport, accumulation and release in the rat brain.

    Gobaille, Serge; Kemmel, Véronique; Brumaru, Daniel; Dugave, Christophe; Aunis, Dominique; Maitre, Michel


    Tryptophan metabolism through the kynurenine pathway leads to several neuroactive compounds, including kynurenic and picolinic acids. Xanthurenic acid (Xa) has been generally considered as a substance with no physiological role but possessing toxic and apoptotic properties. In the present work, we present several findings which support a physiological role for endogenous Xa in synaptic signalling in brain. This substance is present in micromolar amounts in most regions of the rat brain with a heterogeneous distribution. An active vesicular synaptic process inhibited by bafilomycin and nigericin accumulates xanthurenate into pre-synaptic terminals. A neuronal transport, partially dependant on adenosine 5'-triphosphate (ATP), sodium and chloride ions exists in NCB-20 neurons which could participate in the clearance of extracellular xanthurenate. Both transports (neuronal and vesicular) are greatly enhanced by the presence of micromolar amounts of zinc ions. Finally, electrical in vivo stimulation of A10-induced Xa release in the extracellular spaces of the rat prefrontal cortex. This phenomenon is reproduced by veratrine, K+ ions and blocked by EGTA and tetrodotoxin. These results strongly argue for a role for Xa in neurotransmission/neuromodulation in the rat brain, thus providing the existence of specific Xa receptors. PMID:18182052

  8. Histamine induces NF-κB controlled cytokine secretion by orbital fibroblasts via histamine receptor type-1.

    Virakul, Sita; Phetsuksiri, Tanachaporn; van Holten-Neelen, Conny; Schrijver, Benjamin; van Steensel, Leendert; Dalm, Virgil A S H; Paridaens, Dion; van den Bosch, Willem A; van Hagen, P Martin; Dik, Willem A


    Mast cells and their products are likely to be involved in regulating orbital fibroblast activity in Graves' Ophthalmopathy (GO). Histamine is abundantly present in granules of mast cells and is released upon mast cell activation. However, the effect of histamine on orbital fibroblasts has not been examined so far. Orbital tissues from GO patients and controls were analyzed for the presence of mast cells using toluidine blue staining and immunohistochemical detection of CD117 (stem cell factor receptor). Orbital fibroblasts were cultured from GO patients and healthy controls, stimulated with histamine and cytokines (IL-6, IL-8, CCL2, CCL5, CCL7, CXCL10 and CXCL11) were measured in culture supernatants. Also hyaluronan levels were measured in culture supernatants and hyaluronan synthase (HAS) and hyaluronidase (HYAL) gene expression levels were determined. In addition, histamine receptor subtype gene expression levels were examined as well as the effect of the histamine receptor-1 (HRH1) antagonist loratadine and NF-κB inhibitor SC-514 on histamine-induced cytokine production. Mast cell numbers were increased in GO orbital tissues. Histamine stimulated the production of IL-6, IL-8 and CCL2 by orbital fibroblasts, while it had no effect on the production of CCL5, CCL7, CXCL10, CXCL11 and hyaluronan. Orbital fibroblasts expressed HRH1 and loratadine and SC-514 both blocked histamine-induced IL-6, IL-8 and CCL2 production by orbital fibroblasts. In conclusion, this study demonstrates that histamine can induce the production of NF-κB controlled-cytokines by orbital fibroblasts, which supports a role for mast cells in GO. PMID:27170049

  9. Cloning and Sequencing of the Histidine Decarboxylase Genes of Gram-Negative, Histamine-Producing Bacteria and Their Application in Detection and Identification of These Organisms in Fish

    Takahashi, Hajime; Kimura, Bon; Yoshikawa, Miwako; Fujii, Tateo


    The use of molecular tools for early and rapid detection of gram-negative histamine-producing bacteria is important for preventing the accumulation of histamine in fish products. To date, no molecular detection or identification system for gram-negative histamine-producing bacteria has been developed. A molecular method that allows the rapid detection of gram-negative histamine producers by PCR and simultaneous differentiation by single-strand conformation polymorphism (SSCP) analysis using t...

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

    In experiments with rats exposed to 200 Gy radiation it was shown that the diarrhea effect of serotonin under the effect of radiation is implemented via D- and M-type receptors, and that of histamine via H1 and H2 receptors. Serotonin and histamine, that were released under the effect of radiation from endocrine and mast cells of the digestive tract stimulated the propulsion activity of the intestine whereas histamine, in addition, inhibited the absorption process. It is suggested that serotonin and histamine antagonists should be used as means of preventing of radiation-induced diarrhea

  11. Arrhythmogenic Effect of Sympathetic Histamine in Mouse Hearts Subjected to Acute Ischemia

    He, Gonghao; HU, JING; Li, Teng; Ma, Xue; Meng, Jingru; Jia, Min; Lu, Jun; Ohtsu, Hiroshi; Chen, Zhong; Luo, Xiaoxing


    The role of histamine as a newly recognized sympathetic neurotransmitter has been presented previously, and its postsynaptic effects greatly depended on the activities of sympathetic nerves. Cardiac sympathetic nerves become overactivated under acute myocardial ischemic conditions and release neurotransmitters in large amounts, inducing ventricular arrhythmia. Therefore, it is proposed that cardiac sympathetic histamine, in addition to norepinephrine, may have a significant arrhythmogenic eff...

  12. The role of histamine H1 and H4 receptors in allergic inflammation: the search for new antihistamines.

    Thurmond, Robin L; Gelfand, Erwin W; Dunford, Paul J


    Histamine has a key role in allergic inflammatory conditions. The inflammatory responses resulting from the liberation of histamine have long been thought to be mediated by the histamine H1 receptor, and H1-receptor antagonists--commonly known as antihistamines--have been used to treat allergies for many years. However, the importance of histamine in the pathology of conditions such as asthma and chronic pruritus may have been underestimated. Here, we review accumulating evidence suggesting that histamine indeed has roles in inflammation and immune function modulation in such diseases. In particular, the discovery of a fourth histamine receptor (H4) and its expression on numerous immune and inflammatory cells has prompted a re-evaluation of the actions of histamine, suggesting a new potential for H4-receptor antagonists and a possible synergy between H1 and H4-receptor antagonists in targeting various inflammatory conditions. PMID:18172439

  13. Submucosal microinfusion of endothelin and adrenaline mobilizes ECL-cell histamine in rat stomach, and causes mucosal damage: a microdialysis study

    Bernsand, M; Ericsson, P; Björkqvist, M; Zhao, C -M; Håkanson, R; Norlén, P


    Rat stomach ECL cells release histamine in response to gastrin. Submucosal microinfusion of endothelin or adrenaline, known to cause vasoconstriction and gastric lesions, mobilized striking amounts of histamine. While the histamine response to gastrin is sustainable for hours, that to endothelin and adrenaline was characteristically short-lasting (1–2 h).The aims of this study were to identify the cellular source of histamine mobilized by endothelin and adrenaline, and examine the differences...

  14. Sequencing and transcriptional analysis of the streptococcus thermophilus histamine biosynthesis gene cluster: Factors that affect differential hdca expression

    Calles-Enríquez, Marina; Hjort Eriksen, Benjamin; Skov Andersen, Pia; Rattray, F.; Johansen, Annette H.; Fernández García, María; Ladero Losada, Víctor Manuel; Álvarez González, Miguel Ángel


    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 st...

  15. Cimetidine inhibits in vivo growth of human colon cancer and reverses histamine stimulated in vitro and in vivo growth.

    Adams, W J; Lawson, J. A.; Morris, D. L.


    The effect of histamine and cimetidine on the growth of four human colon cancer cell lines was studied. Histamine significantly stimulated the uptake of tritiated thymidine in vitro in a dose dependent manner, to a maximum of 120% and 116% of controls for C170 and LIM2412, respectively. This effect was antagonised by cimetidine, but not diphenhydramine. Histamine also stimulated a dose dependent increase in cyclic adenosine monophosphate accumulation in C170 cells, antagonised by cimetidine. ...

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

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


    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. PMID:25545415

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

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


    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. PMID:25223033

  18. Development of a sensitive radioassay of histamine for in vitro allergy testing

    A radioenzymatic assay for the measurement of histamine is described, based on the incubation of histamine in the presence of histamine-N-methyl-transferase from rat kidney and [3H-methyl]-S-adenosyl-L-methionine (sp act 15 Ci/mmol) in phosphate buffer, 0.05 mole/l, pH 7.9, at 370C for 60 min. The N-[3H-methyl]histamine generated was selectively extracted into toluene/isoamyl alcohol (3:2) and the quantity of the tritium in the sample was determined by liquid-scintillation counting. As little as 1 nmol/l of histamine can be detected. The assay is specific, with no cross-reactivity noted for several compounds closely related to histamine. The assay was used to measure the released histamine of a group of allergic subjects following the incubation of their blood with various allergens. A good correlation was found between histamine release from whole blood and the response of skin mast cells to intradermal antigen administration

  19. Role of histamine in the aetiology of byssinosis. I Blood histamine concentrations in workers exposed to cotton and flax dusts.

    Noweir, M H; Abdel-Kader, H M; Omran, F


    The formation or the accumulation, or both, of histamine in the lungs may be potentiated by agent(s) present in cotton dust at higher level(s) than in flax dust and negligible in cottonseed dust. It has been suggested that such potentiation may be due to the activation of the ability of the lung to produce histamine and/or produce or recruit mast cells; this may present an acceptable explanation of the mechanism by which the propagation of the chronic effect of the dust proceeds in cotton and...

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

    Donskov, F; Middleton, M; Fode, K;


    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...... randomised phase III trial is warranted to clarify the potential role of adding histamine to IL-2 in mRCC....

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

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


    Flies recycle the photoreceptor neurotransmitter histamine by conjugating it to β-alanine to form β-alanyl-histamine (carcinine). The conjugation is regulated by Ebony, while Tan hydrolyses carcinine, releasing histamine and β-alanine. In Drosophila, β-alanine synthesis occurs either from uracil or from the decarboxylation of aspartate but detailed roles for the enzymes responsible remain unclear. Immunohistochemically detected β-alanine is present throughout the fly’s entire brain, and is en...

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

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


    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'. PMID:26107118

  3. Study of the histamine production in a red flesh fish (Sardina pilchardus) and a white flesh fish (Dicentrarchus punctatus)

    (1), M.A. Afilal; (1), H. Daoudi; (2), S. Jdaini; (1), A. Asehraou; *(2), A. Bouali


    The histaminic poisoning, known since 1910, still raises relevant questions. Several authors have agreed that the red flesh fish is more susceptible to accumulate histamine during deterioration, than the white one. This is why this type of food is often involved in this kind of poisoning. High values of histamine concentration (77.7 mg/100g) was observed in sardines having stored for 24 hours at 30°C, while the rate of histamine in white flesh fish, under the same conditions and at the stag...

  4. Histamine in the chick pineal gland: origin, metabolism, and effects on the pineal function.

    Nowak, J Z; Zawilska, J B; Woldan-Tambor, A; Sek, B; Voisin, P; Lintunen, M; Panula, P


    The chick pineal gland contains histamine and tele-methylhistamine. The levels of both substances are elevated after treatment of chicks with the amino acid precursor of histamine, L-histidine (1 g/kg, ip). In control and L-histidine-loaded animals the pineal levels of histamine and tele-methylhistamine are higher in light-exposed than in dark-adapted animals (measured at the end of the light phase and in the middle of the dark phase of 12 hr light, 12 hr dark illumination cycle, respectively). The chick pineal gland contains histamine-immunofluorescent cells displaying mast cell morphology; they are seen in the vicinity of the capsule and in the parenchyma. Enzymatic studies showed the presence of the activity of histamine synthesizing and inactivating enzyme, i.e., L-histidine decarboxylase (HDC) and histamine-methyltransferase (HMT). The detected enzyme activities were sensitive to specific inhibitors of HDC (alpha-fluoromethylhistidine and alpha-hydrazinohistidine) and HMT (quinacrine and metoprine); inhibitors of aromatic amino acid decarboxylase alpha-methyl-DOPA and NSD-1015 were inactive on HDC. Exogenous histamine added to organ-cultured chick pineals strongly stimulated endogenous cyclic AMP accumulation and moderately increased melatonin secretion. The data, considered collectively, suggest that in avians histamine, probably originating from the pineal mast cell compartment, may function as a regulator of pineal gland activity. PMID:9062867

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

    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.

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

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


    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.

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

    Karadag C.H.; Dokmeci D.; Dost T.; Ulugol A.; Dokmeci I.


    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,...

  8. Physiological significance of ECL-cell histamine.

    Andersson, K.; Chen, D; Mattsson, H.; Sundler, F; Håkanson, R


    In the oxyntic mucosa of the mammalian stomach, histamine is stored in ECL cells and in mucosal mast cells. In the rat, at least 80 percent of oxyntic mucosal histamine resides in the ECL cells. Histamine is a key factor in the regulation of gastric acid secretion. Following depletion of ECL-cell histamine by treatment with alpha-fluoromethylhistidine (alpha-FMH), basal acid secretion was reduced, and gastrin-stimulated acid secretion was abolished. Vagally-induced acid secretion (by insulin ...

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

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


    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 (H1 Rs). The phospholipase C inhibitor U-73122 blocked H1 Rs-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 H1 R/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 H1 Rs 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. PMID:26811198

  10. Seasonal methane accumulation and release from a gas emission site in the central North Sea

    Mau, S.; Gentz, T.; Körber, J.-H.; Torres, M. E.; Römer, M.; Sahling, H.; Wintersteller, P.; Martinez, R.; Schlüter, M.; Helmke, E.


    We investigated dissolved methane distributions along a 6 km transect crossing active seep sites at 40 m water depth in the central North Sea. These investigations were done under conditions of thermal stratification in summer (July 2013) and homogenous water column in winter (January 2014). Dissolved methane accumulated below the seasonal thermocline in summer with a median concentration of 390 nM, whereas during winter, methane concentrations were typically much lower (median concentration of 22 nM). High-resolution methane analysis using an underwater mass-spectrometer confirmed our summer results and was used to document prevailing stratification over the tidal cycle. We contrast estimates of methane oxidation rates (from 0.1 to 4.0 nM day-1) using the traditional approach scaled to methane concentrations with microbial turnover time values and suggest that the scaling to concentration may obscure the ecosystem microbial activity when comparing systems with different methane concentrations. Our measured and averaged rate constants (k') were on the order of 0.01 day-1, equivalent to a turnover time of 100 days, even when summer stratification led to enhanced methane concentrations in the bottom water. Consistent with these observations, we could not detect known methanotrophs and pmoA genes in water samples collected during both seasons. Estimated methane fluxes indicate that horizontal transport is the dominant process dispersing the methane plume. During periods of high wind speed (winter), more methane is lost to the atmosphere than oxidized in the water. Microbial oxidation seems of minor importance throughout the year.

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

    Dhanya N


    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.

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

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


    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...

  13. Dexmedetomidine Modulates Histamine-induced Ca2+ Signaling and Pro-inflammatory Cytokine Expression

    Yang, Dongki; Hong, Jeong Hee


    Dexmedetomidine is a sedative and analgesic agent that exerts its effects by selectively agonizing α2 adrenoceptor. Histamine is a pathophysiological amine that activates G protein-coupled receptors, to induce Ca2+ release and subsequent mediate or progress inflammation. Dexmedetomidine has been reported to exert inhibitory effect on inflammation both in vitro and in vivo studies. However, it is unclear that dexmedetomidine modulates histamine-induced signaling and pro-inflammatory cytokine e...

  14. Improved Tumor-Specific Drug Accumulation by Polymer Therapeutics with pH-Sensitive Drug Release Overcomes Chemotherapy Resistance.

    Heinrich, Anne-Kathrin; Lucas, Henrike; Schindler, Lucie; Chytil, Petr; Etrych, Tomáš; Mäder, Karsten; Mueller, Thomas


    The success of chemotherapy is limited by poor selectivity of active drugs combined with occurrence of tumor resistance. New star-like structured N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-based drug delivery systems containing doxorubicin attached via a pH-sensitive hydrazone bond were designed and investigated for their ability to overcome chemotherapy resistance. These conjugates combine two strategies to achieve a high drug concentration selectively at the tumor site: (I) high accumulation by passive tumor targeting based on enhanced permeability and retention effect and (II) pH-sensitive site-specific drug release due to an acidic tumor microenvironment. Mice bearing doxorubicin-resistant xenograft tumors were treated with doxorubicin, PBS, poly HPMA (pHPMA) precursor or pHPMA-doxorubicin conjugate at different equivalent doses of 5 mg/kg bodyweight doxorubicin up to a 7-fold total dose using different treatment schedules. Intratumoral drug accumulation was analyzed by fluorescence imaging utilizing intrinsic fluorescence of doxorubicin. Free doxorubicin induced significant toxicity but hardly any tumor-inhibiting effects. Administering at least a 3-fold dose of pHPMA-doxorubicin conjugate was necessary to induce a transient response, whereas doses of about 5- to 6-fold induced strong regressions. Tumors completely disappeared in some cases. The onset of response was differential delayed depending on the tumor model, which could be ascribed to distinct characteristics of the microenvironment. Further fluorescence imaging-based analyses regarding underlying mechanisms of the delayed response revealed a related switch to a more supporting intratumoral microenvironment for effective drug release. In conclusion, the current study demonstrates that the concept of tumor site-restricted high-dose chemotherapy is able to overcome therapy resistance. Mol Cancer Ther; 15(5); 998-1007. ©2016 AACR. PMID:26939698

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

    Yu ZOU


    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.

  16. Histamine enhances interleukin (IL)-1-induced IL-1 gene expression and protein synthesis via H2 receptors in peripheral blood mononuclear cells. Comparison with IL-1 receptor antagonist.

    Vannier, E; Dinarello, C A


    Histamine and IL-1 have been implicated in the pathogenesis of chronic inflammatory diseases, such as pulmonary allergic reactions and rheumatoid arthritis. We therefore investigated whether histamine modulated the synthesis of IL-1 beta. Human PBMC were stimulated with IL-1 alpha (10 ng/ml) in the absence or presence of histamine (10(-9)-10(-4) M). Histamine alone did not induce protein synthesis or mRNA accumulation for IL-1 beta. IL-1 alpha-induced IL-1 beta synthesis was enhanced two to t...

  17. Radioimmunometric analysis of histamine in myeloproliferative syndromes

    Quantitative analysis of histamine is increasingly used in clinical haematology. The present study demonstrates the properties of and potential indication for a novel histamine radioimmunoassay (RIA) in clinical haematology. The sensitivity of this test assay corresponds to a histamine level of 0,1 to 0,5 nM, the non-specific cross reaction with endogeneous histamine metabolites appears to be less than 0,1%. The total histamine levels in the peripheral blood of healthy donors (n = 10) ranged from 10 to 100 ng/ml, the plasma histamine values from 0,02 to 0,6 ng/ml blood. Increased levels of total histamine were measured in myeloproliferative syndromes, i.e. in patients with chronic myeloid leukemia (CML)(8 of 9), myelofibrosis (OMS)(2 of 4), and polycythaemia vera (PCV)(1 of 2). An excessive increase in total histamine was observed in healthy rhesus monkeys (n = 10) treated with recombinant human interleukin-3 (rhIL-3). The total histamine value correlated with the absolute number of circulating blood basophils (correlation coefficient: 0,9). The calculated content of histamine per basophil was found to be 0,5 to 1,5 pg. Plasma histamine values in patients suffering from myeloproliferative syndromes were within the normal range. In contrast, a moderate to marked increase in plasma histamine values was observed in monkeys during IL-3 treatment. The radioimmunometric analysis of histamine clearly represents a useful new test system in clinical haematology, especially in the follow up of malignant as well as IL-3-induced myeloproliferation. (Authors)

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

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


    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. PMID:26289108

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

    Guoqing Li; Jingtian Yang; Liyuan Yan; Yan Shi


    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 impr...

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

    Rafael Romero-Calderón


    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.

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

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


    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. PMID:26301462

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

    D. Remirez


    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.

  3. High variability of stress accumulation, seismic and aseismic release mode along the Peru-Ecuador subduction zone (Invited)

    Nocquet, J.; Villegas, J. C.; Chlieh, M.; Mothes, P. A.; Rolandone, F.; Jarrín, P.; Cisneros, D.; Vallee, M.


    Most geodetic measurements of interseismic strain along subduction zones have led to the view of coupled asperities of variable size usually separated by narrower zones of low coupling. Along the western margin of South America, fast convergence of the oceanic Nazca plate has repeatedly produced M>8 earthquakes and three of the ten largest megathrust earthquakes since 1900. Contrasting with this behavior, the segment comprised between central Peru and central Ecuador has not experienced any great earthquake for at least five centuries. New GPS measurements in Peru and Ecuador first highlight that a along a ~1000km long segment, convergence is predominantly accommodated by aseismic creep along the plate interface, with possible coupling occurring at shallow depth, close to the trench. This area is bounded by highly locked segments, which produced M>8.5 earthquakes in central Peru and northern Ecuador. While the observed low interseismic coupling explains the lack of great earthquakes, this area has experienced two earthquakes that share the characteristics of tsunamigenic earthquakes, indicating a correlation between the mode of stress accumulation along the plate interface and its release. Finally, we have observed several episodes of slow slip, sometimes associated with intense, micro to moderate seismicity. These observations suggest a specific behavior for this segment, which contrasts with the behavior of the neighboring segments.

  4. Effects of histamine and the histamine antagonists mepyramine and cimetidine on human coronary arteries in vitro.

    Godfraind, Theophile; Miller, R C


    The effects of histamine have been studied on human isolated coronary artery preparations taken from hearts ranging in age from 9 to 73 years. Histamine in large concentrations (100 microM) contracted arteries which were without tone or spontaneous activity and sometimes induced rhythmic contractile activity. If spontaneous rhythmic activity was present it was enhanced by histamine. The contractile effects of histamine were inhibited by mepyramine but not by cimetidine. Arteries which were co...

  5. Effect of histamine and histamine analogues on human isolated myometrial strips.

    Martínez-Mir, M. I.; Estañ, L.; Morales-Olivas, F. J.; Rubio, E.


    1. The effect of histamine and histamine H1- and H2-receptor agonists on isolated myometrium strips of premenopausal women has been examined. The effect of acetylcholine was also determined. 2. Histamine, 2-pyridylethylamine, 4-methylhistamine and acetylcholine, but not dimaprit, produced a concentration-related contractile response in human isolated myometrial strips. Histamine also produced a further contraction in human isolated myometrial strips precontracted with KCl (55 mM). 3. The cont...

  6. Histamine and duodenal ulcer: effect of omeprazole on gastric histamine in patients with duodenal ulcer.

    Man, W K; Thompson, J. N.; Baron, J. H.; Spencer, J


    Gastric mucosal concentrations of histamine and of its metabolic enzyme, histamine methyltransferase activity, were measured in patients with duodenal ulcer disease and patients with an apparently normal stomach and duodenum. Patients with duodenal ulcer had significantly less (p less than 0.05) mucosal histamine (median 204 nmol/g) than control subjects (median 252 nmol/g). There was no significant difference between the two groups in their histamine methyltransferase activity values. Omepra...

  7. Effect of histamine and histamine antagonists on portal blood pressure in patients with hepatosplenic schistosomiasis.

    el-Gendi, M A; Nassar, S H


    1 Histamine injection via the cannulated portal vein significantly raised the portal pressure in normal volunteers. This elevation was reversed by an H1-receptor blocker but not an H2-receptor blocker. When an H1-receptor blocker was injected first followed by histamine, no significant change in portal pressure was obtained. On the other hand, an H2-receptor blocker failed to antagonize the effect of histamine. 2 Histamine injection induced a non-significant increase in the portal pressure in...

  8. Histamine receptors on adult rat cardiomyocytes: antagonism of alpha1-receptor stimulation of cAMP degradation

    Incubation of intact cardiomyocytes with the histamine antagonist [3H]mepyramine results in rapid reversible binding to a single class of high affinity sites (K/sub D/ = 1.2nM; 50,000 sites/myocyte). In membranes from purified myocytes histamine competition of [3H]mepyramine binding (K/sub D/ = 300nM) is not altered by GTP (10μM). Competition of [3H]mepyramine binding by H-receptor subtype-selective antagonists suggests the presence of a single class of H1-receptors. Incubation of intact myocytes with histamine (luM, H1 receptor activation) plus norepinephrine (NE 1uM, alpha1 + beta1 receptor activation) for 3 min leads to significantly more cAMP accumulation (36.5 pmol/106 myocytes) than NE alone (30 pmol/106 myocytes). Histamine alone does not alter basal cAMP = 10.4 pmol/106 myocytes, or beta1 stimulation (isoproternol, 1uM) = 39.6 pmol/106 myocytes. Cyclic AMP accumulation with NE plus prazosin 10nM, (alpha1 + beta1 + alpha1 blockade) is indistinguishable from NE + histamine, (alpha1 + beta1 + H1) stimulation. Histamine competition for [3H]prazosin binding suggests that histamine does not block alpha1 receptors on the myocyte. These data suggest that H1 receptor activation leads to antagonism of the alpha1 receptor mediated activation of cAMP phosphodiesterase the authors have recently described

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

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


    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. PMID:27375247

  10. Histamine in brain development and tumors.

    Panula, P; Lintunen, M; Karlstedt, K


    Histamine is found in developing mammalian brain in both neurons and mast cells. Under normal conditions, histamine H1 and H2 receptors are found in neural, glial and endothelial cells, and H3 receptors at least on neurons. Experimental brain tumors display both H1 and H2 receptors, and histamine increases permeability in the tumors and in the neighboring areas. Many studies have addressed histaminergic signalling mechanisms in cell lines originating from brain tumors. However, the role of histamine in normal development of brain structures, proliferation and differentiation of neurons and glial cells, and growth of malignant tumors in situ is still poorly understood. PMID:10888266

  11. 滨蒿内酯抑制组胺诱导的哮喘豚鼠气道平滑肌细胞内钙释放%Scoparone Suooressed Histamine-induced Intracellular Ca2+ Release in Airway Smooth Muscle Cells from Asthmatic Guineapig

    滕赞; 王嫘; 李智


    Objective Scoparone (Sco) possesses anti - inflammatory and calcium antagonistic effects and it could significantly relax airway smooth muscle (ASM) and decrease cytoplasmic Ca2+ concentration ([Ca2+ ] I) of ASM cells (ASMCs). In this study, the possible pathway of the calcium antagonistic effects of Sco was investigated. Methods ASM strips and cells were derived from normal or ovalbumin - induced asthmatic or Sco pretreated asthmatic guinea - pigs and ASMCs were cultured for 5 to 7 days. Using Fluo- 3/AM staining and a fluorescence spectrophotometer system, the changes of intracellular calcium of cultured ASMCs from each group were measured with or without Sco and histamine. Results The results showed that ASM strips and primary cultured ASMCs from asthmatic guinea - pig maintained the hyper - responsiveness to histamine with different concentrations (P0.05). 10 - 4M Sco also significantly inhibited histamine induced Ca2+ release in cultured ASMCs (P< 0.01). Conclusions Sco shows excellent protection in guinea-pig against histamine - induced ASM contraction by down- regulating hyperactivity of IP3 - induced Ca2+ release in ASMCs from asthmatic guinea pigs.%目的 研究滨蒿内酯(scoparone,Sco)剂量依赖性舒张气管平滑肌及降低气道高反应性的可能作用靶点及途径,为进一步将其开发成为平喘的中药新药提供药理学理论依据.方法 建立卵蛋白诱导的哮喘豚鼠模型,通过离体豚鼠气管环的舒缩实验及应用倒置荧光显微成像系统测定培养的ASMCs[Ca2+]i浓度的方法,分析Sco预先给药及直接作用对ASMCs[Ca2+]i的影响.结果 显示无论细胞外含钙或无钙,组胺具有收缩ASM环及升高培养的ASMC[Ca2+]i作用,哮喘组明显高于对照组(P<0.05),预先给予Sco组与对照组比较差异无统计学意义(P>0.05);在细胞外无钙时10-4MSco直接作用培养的ASMCs,可明显抑制各浓度组胺诱导的ASMCs[Ca2+]i的上升(P<0.05).结论 预先给予Sco及直接

  12. Mast cell-derived histamine mediates cystitis pain.

    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.

  13. Inhaled histamine increases human lung mucociliary transport

    Histamine, a mediator of airways constriction, alters ciliary beat frequency, bronchial mucus production, and epithelial ion transport; and in dogs, increases mucociliary transport. To evaluate the effect of inhaled histamine on human tracheobronchial mucociliary clearance, the authors measured lung mucociliary clearance (LMC) and tracheal mucociliary transport rate (TMTR) in 5 healthy, nonsmoking subjects in a randomized, double-blind, cross-over study. The concentration of inhaled histamine which produced a 20% fall in FEV1 was established for each subject. On a separate day the subjects inhaled a 9 μm MMAD /sup 99m/Tc-Fe2O3 aerosol. LMC and TMTR were then measured for 2.5h using a gamma camera and a tracheal multidetector probe. Simultaneously, the subjects were challenged every 26 +/- 4 min with either PBS or histamine in PBS. The Fe2O3 retained after 24h for histamine (14.4 +/- 7.6%) and PBS studies (13.1 +/- 8.6%) indicated no difference in deposition of Fe2O3 (ANOVA). Fe2O3 clearance at 30 min was increased in the histamine studies (61 +/- 21% compared to the PBS studies (44 +/- 29%; p < 0.02, ANOVA)). TMTR was also increased with histamine (7.6 +/- 3.4 mm/min) compared to PBS (4.6 +/- 1.7 mm/min; p < 0.001, ANOVA). Results indicate an acute stimulatory effect of inhaled histamine on mucous transport in humans

  14. Inhibition of insulin release by cyproheptadine: Effects on 3',5'-cyclic-AMP-content and 45Ca-accumulation of incubated mouse islets

    Cyproheptadine (1, 10 and 100 μm) significantly reduced insulin release from isolated mouse islets in response to glucose. In contrast, 1 mM cyproheptadine induced a large release of insulin into the incubation medium probably due to islet cell damage, since the islets had lost a considerable amount of their protein content. 3',5'-cyclic-AMP-levels of the islets were not significantly affected by 10 μM cyproheptadine in the presence as well as in the absence of theophylline (10 mM). As the inhibitory effect of cyproheptadine on insulin release was correlated with reduced accumulation of calcium-45, the agent may inhibit insulin release by interfering with the calcium handling of the β-cell. (author)

  15. Inhibition of radiation-induced polyuria by histamine receptor antagonists

    In previous studies the authors have demonstrated that gamma radiation results in polyuria, which is preceded by polydypsia. This suggests that the increased thirst elicited by radiation causes increased urinary volume (UV). Histamine, which is released following radiation exposure, also elicits drinking by nonirradiated rats when administered exogenously. In this study the authors have investigated both the role of water deprivation and the effect of histamine receptor antagonists (HRA) on radiation-induced polyuria. Sprague-Dawley rats were housed individually in metabolic cages. Water was allowed ad libitum except in deprivation experiments where water was removed for 24 hr immediately following radiation. Cimetidine (CIM), an H2 HRA, and dexbromopheniramine (DXB), an H1 HRA, were administered i.p. (16 and 1 mg/kg, respectively) 30 min prior to irradiation (950 rads from a cobalt source). UV was determined at 24-hr intervals for 3 days preceding irradiation and 24 hr postirradiation. UV in DXB treated rats was significantly reduced 24 hr postirradiation (CON = 427 +/- 54%; DXB = 247 +/- 39% of preirradiated CON) compared to postirradiation control values. CIM did not affect postirradiation UV. These data suggest that radiation-induced polyuria is caused by polydypsia which is, in part, mediated by histamine induced by an H1 receptor

  16. Methods for preclinical assessment of antipruritic agents and itch mechanisms independent of mast-cell histamine.

    Kuraishi, Yasushi


    Itch is a sensation that provokes a desire to scratch. Mast-cell histamine was thought to be a key itch mediator. However, histamine and mast-cell degranulation were reported not to elicit scratching in animals. It was difficult to investigate the pathophysiology of itching and to evaluate the antipruritic efficacy of chemical agents in the early 1990 s. We showed that hind-paw scratching and biting were elicited by stimulation with pruritogenic agents in mice. Those results demonstrated for the first time that cutaneous itching could be evaluated behaviorally in animals. We established various animal models of pathological itch of the skin (dry skin, mosquito allergy, surfactant-induced pruritus, and herpes zoster) and mucus membranes (pollen allergy). Mast-cell histamine did not play a key role in itching in any animal model examined except for the pollen allergy model. Histamine is not an exclusive itch mediator of mast cells; tryptase and leukotriene B4 released from mast cells also act as itch mediators. Epidermal keratinocytes release several itch mediators, such as leukotriene B4, sphingosylphosphorylcholine, thromboxane A2, nociceptin, nitric oxide, and histamine, which may play important roles in pathological itching. Appropriate animal models of pathological itching are needed for pharmacological evaluation of the antipruritic efficacy of chemical agents. PMID:25947907

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

    The experiments described in this report were designed to test two hypotheses about how exposure to low-level radiation can affect the behavior of an organism: first, tht radiation effects on behavior are mediated by a radiation-induced release of histamine; and second, that this radiation-induced histamine release can exert relatively direct effects on the central nervous system. The results of the first experiment showed that microinjection of histamine directly into the fourth ventricle of rats produced a taste aversion to a novel sucrose solution. Pretreating rats with intraventricular H1 or H2 blockers was not effective in preventing the acquisition of the radiation-induced aversion, although the H1 blocker did prevent the acquisition of a histamine-induced taste aversion. It also was not possible to establish a cross-tolerance between centrally administered histamine and radiation. The results are interpreted as not supporting the hypothesis that a radiation-induced release of central histamine mediates the acquisition of a conditioned taste aversion following exposure to low-level radiation

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

    Chen Eric Y


    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.

  19. Effects of dimethylsulfoxide (DMSO), nocodazole, and taxol on mast cell histamine secretion

    Nielsen, E H; Johansen, Torben


    Nocodazole depolymerized microtubules and increased the number of microfilaments, and dimethylsulfoxide increased the number of microfilaments. Both drugs inhibited compound 48/80-induced histamine release from rat mast cells. Taxol, which increased the number of microtubules, had no effect on hi...

  20. Growth of cultured human glioma tumour cells can be regulated with histamine and histamine antagonists.

    Van der Ven, L. T.; Prinsen, I. M.; Jansen, G H; Roholl, P.J.; Defferrari, R.; Slater, R.; DEN OTTER;, W.


    The 50% survival time for low grade astrocytomas is 50 months and for high grade astrocytomas it is 13 months, underlining the need for new therapies. Several reports show that in vivo histamine antagonists cause retardation of tumour growth in some animal models and prolonged survival in cancer patients. Therefore we have tested the growth modulating effects of histamine and histamine antagonists on human glioma cultures. Twelve freshly excised human gliomas were cultured and tested for thei...

  1. Histamine suppresses gene expression and synthesis of tumor necrosis factor alpha via histamine H2 receptors


    Histamine and tumor necrosis factor alpha (TNF-alpha) can each contribute to the pathogenesis of allergic reactions and chronic inflammatory diseases. We now report the effect of histamine on gene expression and total cellular synthesis of TNF-alpha. Lipopolysaccharide (LPS)-induced synthesis of TNF-alpha in peripheral blood mononuclear cells (PBMC) from 18 healthy donors was suppressed by histamine concentrations from 10(-6) to 10(-4) M, levels comparable with those measured in tissues after...

  2. Histamine H4 receptor antagonists for the treatment of inflammatory disorders.

    Liu, Wai L


    Since its initial discovery by Sir Henry Dale and Patrick Laidlaw in 1910, the biogenic amine histamine has been one of the most widely researched molecules in science. H4R, the newest member of the histamine receptor family, was first identified at the turn of the millennium. Its predominant expression on inflammatory cells and lymphoid tissues, coupled with a key role in processes ranging from chemotaxis to cytokine release, suggests it could command an important role in immune and inflammatory responses. PMID:24859018

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

    M. J. Aguilar; Morales-Olivas, F. J.; Rubio, E.


    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...

  4. Histamine-2 Receptor Antagonists and Semen Quality.

    Banihani, Saleem A


    Histamine-2 receptor antagonists are a class of drugs used to treat the acid-related gastrointestinal diseases such as ulcer and gastro-oesophageal reflux disease. Although such drugs, especially ranitidine and famotidine, are still widely used, their effects on semen quality, and hence on male infertility, is still unclear. This MiniReview systematically addresses and summarizes the effect of histamine-2 receptor antagonists (cimetidine, ranitidine, nizatidine and famotidine) on semen quality, particularly, on sperm function. Cimetidine appears to have adverse effects on semen quality. While the effects of ranitidine and nizatidine on semen quality are still controversial, famotidine does not appear to change semen quality. Therefore, additional studies will be required to clarify whether histamine-2 receptor-independent effects of these drugs play a role in semen quality as well as further clinical studies including direct comparison of the histamine-2 receptor antagonists. PMID:26176290

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

    Ji-Ah Kang

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

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

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


    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

  7. Nitric Oxide and Histamine Signal Attempts to Swallow: A Component of Learning that Food Is Inedible in "Aplysia"

    Katzoff, Ayelet; Miller, Nimrod; Susswein, Abraham J.


    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…

  8. Role of histamine in the aetiology of byssinosis. II. Lung histamine concentrations in guinea pigs chronically exposed to cotton and flax dusts.

    Noweir, M H; Abdel-Kader, H M; Makar, A


    Data presented in this study support the finding that cotton and flax dusts contain agents which potentiate the formation or accumulation of histamine or both in the lungs of guinea pigs exposed to dust, and that such agents are present at much higher levels in cotton dust than in flax dust. The potentiating effect may be through the recruitment of mast cells into the lung. Both cotton and flax dusts contain methylating enzyme inhibitory agents, whereas cotton dust also contains agents that i...

  9. 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.

    Zou, Jinte; Li, Yongmei


    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. PMID:27344244

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

    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


    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. PMID:25662498

  11. Effect of carnosine on the immunosuppressive effect of histamine

    Sharpan, Yu. V.


    This paper studies the ability of carnosine (beta-imidazole-lactate) to affect histamine-induced immunosuppression of proliferative activity of various lymphocyte subpopulations and the realization of this effect through surface histamine receptors of the cells. The experiments were carried out on mice; lymphocytes were incubated with tritium-labeled thymidine for 4 h, after which their radioactivity was determined on a scintillation counter. The results show that histamine has an inhibitory action on antigen-induced proliferation of T suppressor lymphocytes through H-2 histamine receptors, for this effect was considerably inhibited by the H-2 histamine blockers metiamide, but not by the H-1 histamine blocker mepyramine.

  12. Effect of carnosine on the immunosuppressive effect of histamine

    This paper studies the ability of carnosine (beta-imidazole-lactate) to affect histamine-induced immunosuppression of proliferative activity of various lymphocyte subpopulations and the realization of this effect through surface histamine receptors of the cells. The experiments were carried out on mice; lymphocytes were incubated with tritium-labeled thymidine for 4 h, after which their radioactivity was determined on a scintillation counter. The results show that histamine has an inhibitory action on antigen-induced proliferation of T suppressor lymphocytes through H-2 histamine receptors, for this effect was considerably inhibited by the H-2 histamine blockers metiamide, but not by the H-1 histamine blocker mepyramine

  13. The study of helium release, damage accumulation and surface morphology in annealing process of helium-implanted spinel

    Magnesium aluminate spinel(MgAl2O4), due to its excellent radiation resistance, good electrical insulation, high melting point and thermal conductance, has the potential for use as electrical insulator in future fusion reactor. In addition, it is also one of the candidate materials for use as a uranium free inert matrix for the transmutation of minor actinides. Helium accumulation in materials due to a decay and (n, α) nuclear reaction has a severe influence to the mechanism properties. It is therefore of importance to study the helium behavior and damage accumulation in spinel for the application of spinel in nuclear energy field. MgAl2O4(110) single-crystal specimens were implanted with 100 keV 4He+ ions at room temperature to fluences of 0.5, 2 and 8 x 1016 cm-2. The as-implanted samples were annealed at temperature of 500, 700, 900, 1000 and 1100 degree C respectively for 1 hour in vacuum. Different techniques, including Fourier transformed infrared (FTIR) spectroscopy, thermal desorption spectroscopy (TDS), Rutherford back scattering in channeling geometry (RBS-c) and atomic force microscopy (AFM) were adopted subsequently to analyze the samples. It was found that the infra-red absorbance peak corresponding to the Al-O bond vibration shifted to different directions in the as-implantation and annealing processes. At the same time the damage accumulation in spinel showed different behavior depending on implantation dose in the annealing process. The shift of the infra-red absorbance peak and the different damage accumulation behavior are considered to be related with the He agglomeration resulting in the formation of He clusters or He bubbles in spinel. The surface morphology analysis confirmed the formation of helium bubbles below the implanted surface at the higher doses after some annealing process. (authors)

  14. Effects of chloride, sulfate and natural organic matter (NOM) on the accumulation and release of trace-level inorganic contaminants from corroding iron.

    Peng, Ching-Yu; Ferguson, John F; Korshin, Gregory V


    This study examined effects of varying levels of anions (chloride and sulfate) and natural organic matter (NOM) on iron release from and accumulation of inorganic contaminants in corrosion scales formed on iron coupons exposed to drinking water. Changes of concentrations of sulfate and chloride were observed to affect iron release and, in lesser extent, the retention of representative inorganic contaminants (vanadium, chromium, nickel, copper, zinc, arsenic, cadmium, lead and uranium); but, effects of NOM were more pronounced. DOC concentration of 1 mg/L caused iron release to increase, with average soluble and total iron concentrations being four and two times, respectively, higher than those in the absence of NOM. In the presence of NOM, the retention of inorganic contaminants by corrosion scales was reduced. This was especially prominent for lead, vanadium, chromium and copper whose retention by the scales decreased from >80% in the absence of NOM to copper, chromium, zinc and nickel retained on the surface of iron coupons in the presence of DOC largely retained their mobility and were released readily when ambient water chemistry changed. Vanadium, arsenic, cadmium, lead and uranium retained by the scales were largely unsusceptible to changes of NOM and chloride levels. Modeling indicated that the observed effects were associated with the formation of metal-NOM complexes and effects of NOM on the sorption of the inorganic contaminants on solid phases that are typical for iron corrosion in drinking water. PMID:23863395

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

    Poulsen, Steen Seier; Holst, J J


    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...... 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....

  16. The histamine H4 receptor is a potent inhibitor of adhesion-dependent degranulation in human neutrophils.

    Dib, Karim; Perecko, Tomas; Jenei, Veronika; McFarlane, Cheryl; Comer, David; Brown, Vanessa; Katebe, Mwape; Scheithauer, Torsten; Thurmond, Robin L; Chazot, Paul L; Ennis, Madeleine


    The histamine H4 receptor regulates the inflammatory response. However, it is not known whether this receptor has a functional role in human neutrophils. We found that fMLP (1 μM), but not histamine (0.1-1 μM), induced Mac-1-dependent adhesion, polarization, and degranulation (release of lactoferrin). A pretreatment of neutrophils with histamine (0.001-1 μM) or JNJ 28610244 (0.1-10 μM), a specific H4 receptor agonist, led to inhibition of degranulation. Total inhibition of degranulation was obtained with 0.1 μM histamine and 10 μM JNJ 28610244. Furthermore, such inhibition by histamine of degranulation was reversed by JNJ 7777120 and JNJ 28307474, two selective H4 receptor antagonists. However, neither histamine nor the H4 receptor agonist JNJ 28610244 prevented fMLP-induced, Mac-1-dependent adhesion, indicating that the H4 receptor may block signals emanating from Mac-1-controlling degranulation. Likewise, engagement of the H4 receptor by the selective agonist JNJ 28610244 blocked Mac-1-dependent activation of p38 MAPK, the kinase that controls neutrophil degranulation. We also show expression of the H4 receptor at the mRNA level in ultrapure human neutrophils and myeloid leukemia PLB-985 cells. We concluded that engagement of this receptor by selective H4 receptor agonists may represent a good, therapeutic approach to accelerate resolution of inflammation. PMID:24799603

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

    Guoqing Li


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

    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.

  19. Histamine (Scombroid) Fish Poisoning: a Comprehensive Review.

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


    Histamine fish poisoning, also known as scombroid poisoning, is the most common cause of ichythyotoxicosis worldwide and results from the ingestion of histamine-contaminated fish in the Scombroidae and Scomberesocidae families, including mackerel, bonito, albacore, and skipjack. This disease was first described in 1799 in Britain and re-emerged in the medical literature in the 1950s when outbreaks were reported in Japan. The symptoms associated with histamine fish poisoning are similar to that of an allergic reaction. In fact, such histamine-induced reactions are often misdiagnosed as IgE-mediated fish allergy. Indeed, histamine fish poisoning is still an underrecognized disease. In this review, we discuss the epidemiology, pathophysiology, evaluation, and treatment of scombroid disease. Because more than 80% of fish consumed in the USA is now imported from other countries, the disease is intimately linked with the global fish trade (National Marine Fisheries Service, 2012). Preventing future scombroid outbreaks will require that fishermen, public health officials, restaurant workers, and medical professionals work together to devise international safety standards and increase awareness of the disease. The implications of scombroid poisoning go far beyond that of fish and have broader implications for the important issues of food safety. PMID:25876709

  20. Gastrointestinal histamine after thoracic irradiation in the mouse.

    Man, W K; Michalowski, A.; Li, S. K.; Barr, J.; Burgin, J.; Baron, J. H.; Spencer, J


    Thoracic irradiation induced duodenal lesions in mice as an indirect effect. We studied the influence of partial thoracic irradiation on endogenous histamine stores in the alimentary canal. Mice subjected to lower mediastinal irradiation had significantly higher (+19%) median gastric histamine, but lower (-44%) distal duodenal histamine than controls. They also had significantly lower proximal (-39%) and distal (-44%) duodenal histamine than mice who received upper mediastinal irradiation. Tw...


    TERZİ, Göknur; GÜCÜKOĞLU, Ali


    ABSTRACT Histamine is an organic compound with low molecule weight which is formed by the decarboxylation of amino acids as a result of microbiological activity or by animation of aldehydes and ketones. Histamin is present in normally compound of various foods such as fish and fish products, meat and fermented meat products, chicken, cheese, wine and beer. Histamine is formed as a result of the enzymatic decarboxylation of histidine. Histamine causes food poisoning when intake high levels in ...

  2. The effect of sustained release boli with ammoniumiron(III)-hexacyanoferrate(II) on radiocesium accumulation in sheep grazing contaminated pasture

    Sustained release boli with the cesium binder ammoniumiron(III)-hexacyanoferrate(II) (AFCF) were tested under practical conditions for sheep grazing on pastures contaminated with radiocesium (134Cs+137Cs) from the Chernobyl fallout. Two types of AFCF boli were developed: boli without a protective surface coating intended to last 4-8 wk; and boli coated by a wax-mixture with an extended duration of 10-12 wk. From 1989 to 1993 we measured the effect of wax-coated and uncoated boli administered at various times during the grazing season to a total of 3,248 animals. Reductions in radiocesium levels in meat of sheep were measured by in vivo monitoring. Administration of AFCF boli without a wax-coating reduced the mean radiocesium levels in lambs by 42-75% over a 408 wk period, and administration of the wax-coated AFCF boli reduced the mean radiocesium levels by 48-65% over a 9-11 wk period. The coefficients of variation in meat radiocesium levels were similar in treated and control groups at the end of the observation period, showing that the reduction of meat radiocesium values was homogeneous throughout the treated groups. The boli giving sustained release of AFCF is a labor-saving and cost effective counter-measure for sheep grazing radiocesium contaminated pastures. 16 refs., 4 figs., 4 tabs

  3. Histamine and the regulation of body weight

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


    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...... lipolysis. Based on the current evidence of the involvement of histamine in the regulation of body weight, the histaminergic system is an obvious target for the development of pharmacological agents to control obesity. At present, H(3) receptor antagonists that stimulate the histaminergic system may...

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

    The rates of accumulation and subsequent loss of stable cesium (133Cs) by organisms at different trophic levels within plankton-based and periphyton-based food chains were measured following the addition of 133Cs into a small reservoir near Aiken, South Carolina, USA. An uptake parameter u (L kg-1 d-1 dry mass) and a loss rate parameter k (d-1) were estimated for each organism using time-series measurements of 133Cs concentrations in water and biota, and these parameters were used to estimate maximum concentrations, times to maximum concentrations, and concentration ratios (Cr). The maximum 133Cs 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 Cr based on dry mass for plankton and C. punctipennis were 1220 L kg-1 and 5570 L kg-1, respectively, and were less than the Cr of 8630 L kg-1 for periphyton and 47,700 L kg-1 for H. trivolvis. Although the Cr differed between plankton-based and periphyton-based food chains, they displayed similar levels of biomagnification. Biomagnification was also indicated for fish where the Cr for the mostly nonpiscivorous L. macrochirus of 22,600 L kg-1 was three times less than that for mostly piscivorous M. salmoides of 71,500 L kg-1. Although the Cr for M. salmoides was greater than those for periphyton and H. trivolvis, the maximum 133Cs concentrations for periphyton and H. trivolvis were greater than that for M. salmoides. - Research highlights: → A simple uptake and loss model described the Cs dynamics in all the various biota. → Concentrations of Cs were greater in periphyton than in plankton. → Biota other than fish demonstrated the greatest maximum Cs concentrations. → Concentration ratios were generally consisted

  5. Klebsiella pneumoniae Produces No Histamine: Raoultella planticola and Raoultella ornithinolytica Strains Are Histamine Producers

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


    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 H...

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

    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.

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

    D. Remirez; N. Ledón; R. González


    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 300mg/kg post-orally (p.o.)) was administered 1 h ...

  8. Histamine is required for H3 receptor-mediated alcohol reward inhibition, but not for alcohol consumption or stimulation

    Vanhanen, J; Nuutinen, S; Lintunen, M; Mäki, T; Rämö, J; Karlstedt, K; Panula, P


    Background and Purpose Conflicting data have been published on whether histamine is inhibitory to the rewarding effects of abused drugs. The purpose of this study was to clarify the role of neuronal histamine and, in particular, H3 receptors in alcohol dependence-related behaviours, which represent the addictive effects of alcohol. Experimental Approach Alcohol-induced conditioned place preference (alcohol-CPP) was used to measure alcohol reward. Alcohol-induced locomotor stimulation, alcohol consumption and kinetics were also assessed. mRNA levels were quantified using radioactive in situ hybridization. Key Results Low doses of H3 receptor antagonists, JNJ-10181457 and JNJ-39220675, inhibited alcohol reward in wild-type (WT) mice. However, these H3 receptor antagonists did not inhibit alcohol reward in histidine decarboxylase knock-out (HDC KO) mice and a lack of histamine did not alter alcohol consumption. Thus H3 receptor antagonists inhibited alcohol reward in a histamine-dependent manner. Furthermore, WT and HDC KO mice were similarly stimulated by alcohol. The expression levels of dopamine D1 and D2 receptors, STEP61 and DARPP-32 mRNA in striatal subregions were unaltered in HDC KO mice. No differences were seen in alcohol kinetics in HDC KO compared to WT control animals. In addition, JNJ-39220675 had no effect on alcohol kinetics in WT mice. Conclusions and Implications These data suggest that histamine is required for the H3 receptor-mediated inhibition of alcohol-CPP and support the hypothesis that the brain histaminergic system has an inhibitory role in alcohol reward. Increasing neuronal histamine release via H3 receptor blockade could therefore be a novel way of treating alcohol dependence. Linked Articles This article is part of a themed issue on Histamine Pharmacology Update. To view the other articles in this issue visit PMID:23489295

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

    Karadag C.H.


    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.

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

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


    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. PMID:26939881

  11. The histamine degradative uptake pathway in human vascular endothelial cells and skin fibroblasts is dependent on extracellular Na+ and Cl-

    We have previously reported that human vascular endothelial cells and skin fibroblasts carry out degradation of [3H]histamine by a mechanism involving two successive enzymatic steps: imidazole ring tele-methylation by the cells' endogenous methyltransferase and subsequent amine oxidation by an exogenous diamine oxidase. Both histamine and the exogenous second enzyme in the pathway associate with the cells via separate binding sites or receptors. The enzymatic degradation process results in cellular accumulation of the proximal and distal metabolites tele-methylhistamine and 1-methyl-4-imidazoleacetic acid (MIAA). We have now demonstrated that this two-stage histamine degradative pathway is dependent on Na+ and Cl- in the extracellular environment. Accumulation of [3H] histamine-derived products is partially inhibited under conditions of Na+ deprivation and more substantially when Cl- is also withdrawn. The individual tele-methylation and amine oxidation enzymatic reactions themselves are unaffected or actually facilitated under these conditions. This indicates that it is the cellular mechanism for uptake coupled to the degradative pathway which reflects the cation and anion dependency. Restoration of degradative uptake displays a biphasic Na+ concentration curve, suggesting that the uptake process may be driven by multiple components. These findings indicate a role for both inward Na+ and Cl- ion movement in this cellular degradative uptake mechanism

  12. Histamine bronchial challenge: effect on regional ventilation and aerosol deposition.

    Clague, H.; Ahmad, D.; Chamberlain, M. J.; Morgan, W K; Vinitski, S


    We studied regional changes in ventilation and aerosol deposition after histamine challenge in six patients with asthma and two with rhinitis and a history of wheezing. All were known to have bronchial hyperreactivity and all showed an increased response to histamine. Ventilation and aerosol deposition studies, using xenon-133 and an aerosol of sulphur colloid tagged with technetium 99m, were performed while they were sitting. Before administration of histamine radioaerosol scintiscans were a...

  13. Methodology for histamine and biogenic amines analysis. Seafoodplus Traceability

    Etienne, Monique


    Histamine, putrescine, cadaverine, tyramine and agmatine are produced from the decarboxylation of histidine, ornithine, lysine tyrosine and arginine respectively. Histamine is associated of scombroid poisoning in conjonction with the ingestion of some fish species such as tuna, mackerel, sardine, herring,anchovy. The formation of histamine in fish products is directly correlated with the concentration of histidine in the tissue and the level of microorganisms present in the product, due to ...

  14. Reflex effects of aerosolized histamine on phrenic nerve activity.

    Pack, A I; Hertz, B C; Ledlie, J F; Fishman, A. P.


    Studies were conducted in anesthetized, paralyzed dogs on the effect of aerosolized histamine on phrenic nerve activity. The paralyzed dogs were ventilated in phase with their recorded phrenic nerve activity at a constant inspiratory flow-rate, using a cycle-triggered ventilator. Phrenic nerve activity was measured before and during administration of aerosolized histamine while the inspiratory flow-rate and arterial blood gases were kept constant. In addition, before and after histamine, phre...

  15. Mechanism of histamine-induced excitation of the cat pylorus.

    Biancani, P.; CiCalzi, L K; McCallum, R. W.


    Intravenous histamine causes high amplitude repetitive phasic contractions of the in vivo cat pylorus but has little effect on the antrum and duodenum. The genesis of this phasic response was studied using a pinned perfused catheter with openings at the pylorus, antrum, and duodenum. 2-Pyridylethylamine, an H1 agonist, produced phasic contractions similar to histamine whereas dimaprit, an H2 agonist, did not. Conversely, histamine-induced excitation is competitively antagonized by the H1 inhi...

  16. Positive inotropic effects of histamine in anaesthetized dogs.

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


    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...

  17. Histamine N-methyltransferase Modulates Human Bronchial Smooth Muscle Contraction

    Tamaoki, J.; Chiyotani, A.; Tagaya, E; Isono, K; Konno, K


    To elucidate the modulatory role of histamine-degrading enzymes in airway constrictor responses, human bronchial strips were studied under isometric conditions in vitro. Pretreatment of tissues with the histamine N-methyltransferase (HMT) inhibitor SKF 91488 specifically potentiated the contractile responses to histamine, causing a leftward displacement of the concentration response curves, whereas the diamine oxidase inhibitor aminoguanidine had no effect. This potentiation was attenuated by...

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

    Sha, Quan; Poulsen, Lars K.; Gerwien, Jens; Ødum, Niels; Skov, Per Stahl


    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 ...

  19. CPB1 of Aedes aegypti Interacts with DENV2 E Protein and Regulates Intracellular Viral Accumulation and Release from Midgut Cells

    Hong-Wai Tham


    Full Text Available Aedes aegypti is a principal vector responsible for the transmission of dengue viruses (DENV. To date, vector control remains the key option for dengue disease management. To develop new vector control strategies, a more comprehensive understanding of the biological interactions between DENV and Ae. aegypti is required. In this study, a cDNA library derived from the midgut of female adult Ae. aegypti was used in yeast two-hybrid (Y2H screenings against DENV2 envelope (E protein. Among the many interacting proteins identified, carboxypeptidase B1 (CPB1 was selected, and its biological interaction with E protein in Ae. aegypti primary midgut cells was further validated. Our double immunofluorescent assay showed that CPB1-E interaction occurred in the endoplasmic reticulum (ER of the Ae. aegypti primary midgut cells. Overexpression of CPB1 in mosquito cells resulted in intracellular DENV2 genomic RNA or virus particle accumulation, with a lower amount of virus release. Therefore, we postulated that in Ae. aegypti midgut cells, CPB1 binds to the E protein deposited on the ER intraluminal membranes and inhibits DENV2 RNA encapsulation, thus inhibiting budding from the ER, and may interfere with immature virus transportation to the trans-Golgi network.

  20. Effect of pentagastrin on histamine output from the stomach in patients with duodenal ulcer.

    Man, W K; Saunders, J H; Ingoldby, C; Spencer, J


    The role of histamine in acid secretion is controversial. Improvements in the techniques of histamine assay allow a better assessment of the relationship of histamine to acid secretion. Patients with duodenal ulcers were studied to determine the mucosal histamine responses to pentagastrin stimulation to relate the appearance of histamine in the gastric juice to acid production during stimulation, and to detect changes in the plasma histamine concentration during pentagastrin stimulation. Ther...

  1. Development of a homogeneous binding assay for histamine receptors.

    Crane, Kathy; Shih, Daw-Tsun


    Histamine is critically involved in a wide range of physiological and pathological processes through its actions at different receptors. Thus, histamine receptors have been actively pursued as therapeutic targets in the pharmaceutical industry for the treatment of a variety of diseases. There are currently four histamine receptors that have been cloned, all of which are G protein-coupled receptors. Studies from both academia and pharmaceutical companies have identified compounds that modulate the function of specific histamine receptors. These efforts led to the successful introduction of histamine H(1) and H(2) receptor antagonists for the treatment of allergy and excess gastric acid secretion, respectively. Histamine H(3) receptor ligands are currently under investigation for the treatment of obesity and neurological disorders. The recently identified histamine H(4) receptor is preferentially expressed in the immune tissues, suggesting a potential role in normal immune functions and possibly in the pathogenesis of inflammatory diseases. Even with the long history of histamine research and the important applications of histamine receptor ligands, assays to measure the affinity of compounds binding to histamine receptors are still routinely analyzed using a filtration assay, a very low-throughput assay involving washing and filtration steps. This article describes a simple, robust, and homogeneous binding assay based on the scintillation proximity assay (SPA) technology that provides results equivalent to those obtained using the more complex filtration assay. The SPA format is easily adapted to high-throughput screening because it is amenable to automation. In summary, this technique allows high-throughput screening of compounds against multiple histamine receptors and, thus, facilitates drug discovery efforts. PMID:15519569

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

    Rapanelli, Maximiliano; Pittenger, Christopher


    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'. PMID:26282120

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

    Cakir, Ziyadin


    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.

  4. Ouabain enhancement of compound 48/80 induced histamine secretion from rat peritoneal mast cells

    Purified populations of rat peritoneal mast cells were used to study the effect of ouabain on compound 48/80-induced histamine secretion and on 86Rb+ uptake. 86Rb+ was used as a tracer for extracellular K+. The calculated value of the ouabain-sensitive uptake of K+ and 86Rb+ was considered a measure of the Na+-K+ pump activity of the cells. Ouabain caused an immediate inhibition of the pump activity and a time-dependent increase in histamine secretion in the absence of extracellular calcium. No effect on the secretion was observed in the presence of calcium. The effect of ouabain on the secretion occurs in the presence of sodium but not when sodium was replaced by lithium. Preservation by ouabain of a high intracellular sodium content in sodium-loaded cells was associated with preservation of the secretory response in a calcium-free medium. In the presence of lanthanum in a calcium-free medium, the pump activity was inhibited and the enhancement by ouabain of the secretion of histamine was blocked. A less marked inhibition of the pump was found in a calcium-free medium containing magnesium. The inhibition exerted by magnesium was concentration-dependent (0-5 mM) as was the counteraction of magnesium of the enhancement of ouabain of the secretion of histamine. These observations indicate that the echancement by ouabain of the secretory response of mast cells preincubated in a calcium-free medium is associated with accumulation of sodium inside the cell. In addition to a decreased rate of sodium-calcium exchange caused by a decreased inward directed sodium gradient, the mechanism by which ouabain enhances the secretory response is likely to involve an increased binding of calcium to membrane binding sites. (au)

  5. Quantitative Single-Cell Analysis of Signaling Pathways Activated Immediately Downstream of Histamine Receptor Subtypes.

    van Unen, Jakobus; Rashidfarrokhi, Ali; Hoogendoorn, Eelco; Postma, Marten; Gadella, Theodorus W J; Goedhart, Joachim


    Genetically encoded biosensors based on Förster resonance energy transfer (FRET) can visualize responses of individual cells in real time. Here, we evaluated whether FRET-based biosensors provide sufficient contrast and specificity to measure activity of G-protein-coupled receptors. The four histamine receptor subtypes (H1R, H2R, H3R, and H4R) respond to the ligand histamine by activating three canonical heterotrimeric G-protein-mediated signaling pathways with a reported high degree of specificity. Using FRET-based biosensors, we demonstrate that H1R activates Gαq. We also observed that H1R activates Gαi, albeit at a 10-fold lower potency. In addition to increasing cAMP levels, most likely via Gαs, we found that the H2R induces Gαq-mediated calcium release. The H3R and H4R activated Gαi with high specificity and a high potency. We demonstrate that a number of FRET sensors provide sufficient contrast to: 1) analyze the specificity of the histamine receptor subtypes for different heterotrimeric G-protein families with single-cell resolution, 2) probe for antagonist specificity, and 3) allow the measurement of single-cell concentration-response curves. PMID:27358232

  6. Mechanisms of histamine stimulated secretion in rabbit ileal mucosa.

    Linaker, B D; McKay, J S; Higgs, N B; Turnberg, L A


    Histamine is present in high concentrations in the intestine and we investigated the possibility that it might have a role here in intestinal transport. When added to the basal side of rabbit ileal mucosa in vitro histamine (10(-4)M) induced a short-lived increase in electrical potential difference and short circuit current. It inhibited net chloride absorption but did not influence sodium transport. Alkali secretion, measured by a pH stat technique, was inhibited, suggesting that bicarbonate secretion was reduced. Both the electrical and ion flux responses to histamine were blocked by the H1 receptor blocker diphenhydramine, but not by the H2 receptor blocker cimetidine. The presence of specific H1 histamine receptors was further supported by shifts in the dose-response curve to histamine by four different concentrations of diphenhydramine. Calculation of a pA2 value from these "Schild' plots provided a figure of 7.85, which is similar to that for H1 receptors in other tissues. Aminoguanidine, a histaminase blocker, had no electrical effects alone but shifted the histamine dose response curve to the left. These studies indicate that histamine inhibits chloride absorption and alkali secretion, possibly by influencing a chloride/bicarbonate exchange process, through specific mucosal H1 receptors. Enhancement of histamine effects by a histaminase inhibitor suggests that histaminases are present in the intestinal mucosa and supports the possibility of a role for endogenous histamine in influencing ion transport. The observations indicate a mechanism by which absorption might be impaired in diseases in which histamine is liberated locally in the intestine. PMID:7308851


    When cattle and horses are fed large amounts of grain, histamine can accumulate in the gastrointestinal tract, and this accumulation can cause an acute inflammation of the hooves (laminitis). When ruminal fluid from dairy cattle fed grain supplements was serially diluted in anaerobic MRS medium con...

  8. Azines as histamine H4 receptor antagonists.

    Lazewska, Dorota; Kiec-Kononowicz, Katarzyna


    Since 2000, when the histamine H4 receptor (H4R) was cloned, it has constituted an interesting target for drug development. Pharmacological studies suggest the potential utility of histamine H4R antagonists/inverse agonists in the treatment of inflammatory diseases, e.g. allergic rhinitis, asthma, atopic dermatitis, colitis, or pruritus. The first H4R ligands were non-selective compounds, but intensive chemical and pharmacological work has led to the discovery of highly potent and selective H4R antagonists (e.g. JNJ7777120, CZC-13788, PF-2988403, A-940894, A-987306). The first compound (UR-63325) has finally entered into clinical studies for the treatment of allergic respiratory diseases (completing the phase I ascending dose trial) and has been found to be safe and well tolerated. The number of scientific publications and patent applications in the H4 field is increasing annually. Among the diverse chemical structures of the H4R antagonists described a 2-aminopyrimidine scaffold is repeatedly found. This review looked at recent advances in the search for H4R antagonists as reflected in patent applications/patents and peer-reviewed publications over the last two years. The work concerns azines (mono-, di-, triazines) and their fused analogues. The chemistry and pharmacology has been described. PMID:22202103

  9. Histamine Potentiates Cyclosomatostatin-Induced Catalepsy in Old Rats



    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.

  10. A comparison of the effects of divalent and trivalent cations on parathyroid hormone release, 3',5'-cyclic-adenosine monophosphate accumulation, and the levels of inositol phosphates in bovine parathyroid cells.

    Brown, E M; Fuleihan G el-H; Chen, C J; Kifor, O


    We compared the effects of a series of di- and trivalent cations on various aspects of parathyroid function to investigate whether these polyvalent cations act on the parathyroid cell through a similar mechanism. Like high extracellular concentrations of Ca2+, high levels of barium (Ba2+), strontium (Sr2+), gadolinium (Gd3+), europium (Eu3+), terbium (Tb3+), and ytterbium (Yb3+) [corrected] each inhibited low calcium-stimulated PTH release and showed IC50 values (the concentration producing half of the maximal inhibitory effect) of 1.12 mM, 1.18 mM, 2.2 microM, 2.5 microM, 0.89 microM, and 15 microM, respectively. The inhibitory effects of both divalent (Ca2+ and Ba2+) and trivalent (Gd3+) cations were reversible by 76-100% after removal of the cation, suggesting that the polyvalent cation-mediated reduction in PTH release was not due to nonspecific toxicity. The same di- and trivalent cations produced an 80-90% decrease in agonist-stimulated cAMP accumulation with a similar order of potency as for their effects on PTH release. Preincubation overnight with pertussis toxin totally prevented the inhibitory effects of the trivalent cations on cAMP accumulation. The same di- and trivalent cations also increased the accumulation of inositol monophosphate, inositol bisphosphate, and inositol trisphosphate. Their effects on this parameter differed from those on PTH release and cAMP accumulation in several respects. First, Ba2+ and Sr2+, rather than being equipotent with Ca2+, were about 2-fold less potent in increasing the levels of inositol phosphates. Second, the trivalent cations were 5-50-fold less potent in raising inositol phosphates than in modulating PTH release and cAMP accumulation, and all were nearly equipotent. These results show that trivalent cations of the lanthanide series mimic the actions of divalent cations on several aspects of parathyroid function, and likely do so by interacting with the cell surface "Ca2(+)-receptor-like mechanism" through which