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Sample records for histamine releasing factor

  1. The American dog tick, Dermacentor variabilis, encodes a functional histamine release factor homolog.

    PubMed

    Mulenga, Albert; Macaluso, Kevin R; Simser, Jason A; Azad, Abdu F

    2003-09-01

    We have identified a functional Dermacentor variabilis histamine release factor (DVHRF) homolog and shown that it is a secreted tick saliva protein. The 945 base pair (bp) full-length DVHRF cDNA has a 522 bp open reading frame that encodes a 20 kDa (173 amino acid) polypeptide. Sequence analysis showed that the two HRF signature amino acid sequences were conserved in DVHRF, indicating close structural similarity between DVHRF and other characterized HRF homologs. Northern and Western blotting analyses of partially fed and unfed ticks indicates that neither DVHRF transcriptional nor translational regulation were influenced by tick feeding activity. Like its counterparts from the mammalian system, tick DVHRF is expressed in various tissues, as assessed by both Northern and Western blotting analyses. Furthermore, an Escherichia coli-expressed recombinant DVHRF induced histamine secretion from a rat basophilic leukemic cell line in a dose-dependent manner. Extensive experimental evidence has shown that high levels of histamine at tick attachment sites impede the biological success of feeding ticks and, in response, ticks secrete histamine-binding proteins to minimize the adverse effects of histamine. Our results suggest the existence of a tick-derived multifaceted control mechanism for levels of histamine at tick feeding sites.

  2. 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

    SciTech Connect

    Alam, R.; Welter, J.B.; Forsythe, P.A.; Lett-Brown, M.A.; Grant, J.A. )

    1989-05-15

    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 D{sub 2}O. 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.

  3. Exercise-induced release of histamine and neutrophil chemotactic factor in atopic asthmatics.

    PubMed

    Lee, T H; Brown, M J; Nagy, L; Causon, R; Walport, M J; Kay, A B

    1982-08-01

    Concentrations of plasma histamine and serum neutrophil chemotactic factor (NCF) were measured in seven atopic asthmatics who developed exercise-induced asthma (EIA) after a treadmill task. The results were compared with those obtained after inhalation of specific antigen or methacholine. Plasma histamine concentrations were measured with a novel double-isotope radiometric assay, and NCF was identified by its elution in the void volume fractions of Sephadex G-200 and as a single peak of activity at approximately 0.20 molar NaCl after anion exchange chromatography on diethylaminoethyl-Sephacel (pH 7.8). After exercise or antigen challenge, the time courses of appearance of both mediators were virtually identical and accompanied the increase in airways obstruction. There was a statistically significant correlation between the concentrations of histamine or NCF and the magnitude of airflow obstruction after exercise and antigen challenge. This suggested that there may be a direct association between mediator release and EIA or antigen-induced bronchoconstriction. In contrast, there were no significant elevations in circulating histamine and NCF after inhalation of methacholine, at concentrations giving a fall in FEV1 comparable to that induced by exercise or antigen. The prior administration of cromolyn to three asthmatics inhibited both their EIA and the release of histamine and NCF. When four asthmatics were exercised for periods of 1, 3, and 6 min, the release of NCF and fall in peak expiratory flow rate were directly related to the duration of the exercise. The rise of NCF activity in subjects with EIA was fivefold greater than that observed in asthmatics who did not experience airways obstruction when subjected to the same exercise task. These results provide further evidence that mediators of hypersensitivity are released during EIA.

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

    PubMed

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

    2003-12-15

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

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

    PubMed

    Mulenga, Albert; Azad, Abdu F

    2005-01-01

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

  6. Tick Histamine Release Factor Is Critical for Ixodes scapularis Engorgement and Transmission of the Lyme Disease Agent

    PubMed Central

    Dai, Jianfeng; Narasimhan, Sukanya; Zhang, Lili; Liu, Lei; Wang, Penghua; Fikrig, Erol

    2010-01-01

    Ticks are distributed worldwide and affect human and animal health by transmitting diverse infectious agents. Effective vaccines against most tick-borne pathogens are not currently available. In this study, we characterized a tick histamine release factor (tHRF) from Ixodes scapularis and addressed the vaccine potential of this antigen in the context of tick engorgement and B. burgdorferi transmission. Results from western blotting and quantitative Reverse Transcription-PCR showed that tHRF is secreted in tick saliva, and upregulated in Borrelia burgdorferi-infected ticks. Further, the expression of tHRF was coincident with the rapid feeding phase of the tick, suggesting a role for tHRF in tick engorgement and concomitantly, for efficient B. burgdorferi transmission. Silencing tHRF by RNA interference (RNAi) significantly impaired tick feeding and decreased B. burgdorferi burden in mice. Interfering with tHRF by actively immunizing mice with recombinant tHRF, or passively transferring tHRF antiserum, also markedly reduced the efficiency of tick feeding and B. burgdorferi burden in mice. Recombinant tHRF was able to bind to host basophils and stimulate histamine release. Therefore, we speculate that tHRF might function in vivo to modulate vascular permeability and increase blood flow to the tick bite-site, facilitating tick engorgement. These findings suggest that blocking tHRF might offer a viable strategy to complement ongoing efforts to develop vaccines to block tick feeding and transmission of tick-borne pathogens. PMID:21124826

  7. Immunological memory to blood-stage malaria infection is controlled by the histamine releasing factor (HRF) of the parasite.

    PubMed

    Demarta-Gatsi, Claudia; Peronet, Roger; Smith, Leanna; Thiberge, Sabine; Ménard, Robert; Mécheri, Salaheddine

    2017-08-22

    While most subunit malaria vaccines provide only limited efficacy, pre-erythrocytic and erythrocytic genetically attenuated parasites (GAP) have been shown to confer complete sterilizing immunity. We recently generated a Plasmodium berghei (PbNK65) parasite that lacks a secreted factor, the histamine releasing factor (HRF) (PbNK65 hrfΔ), and induces in infected mice a self-resolving blood stage infection accompanied by a long lasting immunity. Here, we explore the immunological mechanisms underlying the anti-parasite protective properties of the mutant PbNK65 hrfΔ and demonstrate that in addition to an up-regulation of IL-6 production, CD4(+) but not CD8(+) T effector lymphocytes are indispensable for the clearance of malaria infection. Maintenance of T cell-associated protection is associated with the reduction in CD4(+)PD-1(+) and CD8(+)PD-1(+) T cell numbers. A higher number of central and effector memory B cells in mutant-infected mice also plays a pivotal role in protection. Importantly, we also demonstrate that prior infection with WT parasites followed by a drug cure does not prevent the induction of PbNK65 hrfΔ-induced protection, suggesting that such protection in humans may be efficient even in individuals that have been infected and who repeatedly received antimalarial drugs.

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

    PubMed

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

    2009-03-01

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

  9. Release of platelet-activating factor (PAF) and histamine. II. The cellular origin of human PAF: monocytes, polymorphonuclear neutrophils and basophils.

    PubMed Central

    Camussi, G; Aglietta, M; Coda, R; Bussolino, F; Piacibello, W; Tetta, C

    1981-01-01

    The origin of platelet activating factor (PAF) from human leucocytes was investigated. Purified monocytes release PAF passively at pH 10.6, when challenged with Ionophore A 23187 or under phagocytic stimuli. Pure preparations of polymorphonuclear neutrophils liberate PAF passively, when challenged with C5a, neutrophil cationic proteins (CP), their carboxypeptidase B derived products (C5a des Arg, CP des Arg) or under phagocytic stimuli. Basophil rich buffy coat cells release PAF when challenged with C5a, CP, anti-IgE (in low amount) or Synacthen concomitantly with basophil degranulation and histamine release. Electron microscopy studies, carried out on Synacthen-stimulated basophil rich buffy coat, provide morphological evidence for platelet-basophil interaction. In conclusion our data demonstrate that PAF can be released from different leucocyte populations. However, the stimuli able to trigger such release appear to have some specificity for the cell target. Images Figure 5 PMID:6161885

  10. Ammonium and sulfate ion release of histamine from lung fragments.

    PubMed

    Charles, J M; Menzel, D B

    1975-06-01

    In vitro studies with guinea pig lung fragments incubated with 10- to 200-mM concentrations of ammonium ion demonstrated the release of substanial quantities of histamine. Of the anions tested with ammonium ion, sulfate was the most potent, while nitrate and acetate ions were of intermediate potency and chloride was less potent. An osmotic effect is unlikely since equal concentrations of sodium chloride failed to release histamine. Isoproterenol, known to decrease anaphylactic histamine release, and acetycholine, known to increase histamine release, had no effect on the ammonium sulfate-mediated release of histamine. N-6 2'-O-Dibutyryladenosine 3',5' monophosphate (dibutyryl c-AMP) was also ineffective. These studies suggest that the inhalation irritation associated with certain sulfate and other salts, may be a function of their ability to release histamine in the presence of amonium ion.

  11. Influence of bronchial allergen challenge on histamine release by human basophils.

    PubMed

    Lie, W J; Van Der Veen, M J; Knol, E F; Mul, F P; Jansen, H M; Roos, D; Van Der Zee, J S

    2000-06-01

    Basophils can be primed by cytokines such as interleukin (IL) -3, IL-5 or granulocyte macrophage-colony stimulating factor (GM-CSF). It has been described that the concentrations of these cytokines are enhanced at sites of allergic inflammation as well as systemic in allergic asthma. To investigate the priming status of basophils as detected by thapsigargin-induced histamine release during bronchial allergen challenge. Ten subjects allergic to house dust mite were challenged via an aerosol delivery system. Spontaneous leucocyte histamine release as well as histamine release induced by various stimuli was measured in vitro at several time points. In addition, lung function parameters, serum IL-5 and blood eosinophil counts were evaluated. We found no effect of bronchial allergen challenge upon spontaneous leucocyte histamine release, nor upon histamine release induced by anti-immunoglobulin (Ig) E, house dust mite extract, C5a, fMLP, IL-3, PMA+ thapsigargin or IL-3+ thapsigargin. However, the priming status of basophils as measured by thapsigargin-induced histamine release was enhanced at 24 h after bronchial allergen challenge. Analysis of the individual data showed a heterogeneous initial response (30 min, 6 h) followed by a predominant increase at 24 h after allergen challenge. This increase in the thapsigargin-induced histamine release correlated with the increase in serum IL-5 levels at 24 h after allergen challenge. The priming status of human basophils as measured by thapsigargin-induced histamine release is enhanced 24 h after allergen challenge.

  12. Plasmodium berghei histamine-releasing factor favours liver-stage development via inhibition of IL-6 production and associates with a severe outcome of disease.

    PubMed

    Mathieu, Cédric; Demarta-Gatsi, Claudia; Porcherie, Adeline; Brega, Sara; Thiberge, Sabine; Ronce, Karine; Smith, Leanna; Peronet, Roger; Amino, Rogerio; Ménard, Robert; Mécheri, Salaheddine

    2015-04-01

    Plasmodium spp., which causes malaria, produces a histamine-releasing factor (HRF), an orthologue of mammalian HRF. Histamine-releasing factor produced by erythrocytic stages of the parasite is thought to play a role in the pathogenesis of severe malaria. Here, we show in a rodent model that HRF is not important during the erythrocytic but pre-erythrocytic phase of infection, which mainly consists in the transformation in the liver of the mosquito-injected parasite form into the erythrocyte-infecting form. Development of P. berghei ANKA cl15cy1 liver stages lacking HRF is impaired and associated with an early rise in systemic IL-6, a cytokine that strongly suppresses development of Plasmodium liver stages. The defect is rescued by injection of anti-IL-6 antibodies or infection in IL-6-deficient mice and parasite HRF is sufficient to decrease IL-6 synthesis, indicating a direct role of parasite HRF in reducing host IL-6. The target cells modulated by HRF for IL-6 production at early time points during liver infection are neutrophils. Parasite HRF is thus used to down-regulate a cytokine with anti-parasite activity. Our data also highlight the link between a prolonged transition from liver to blood-stage infection and reduced incidence of experimental cerebral malaria. © 2014 John Wiley & Sons Ltd.

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

    PubMed

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

    2003-03-20

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

  14. Infralimbic cortex activation and motivated arousal induce histamine release.

    PubMed

    Riveros, María Eugenia; Forray, María Inés; Torrealba, Fernando

    2015-06-01

    Appetitive behaviours occur in a state of behavioural and physiological activation that allows the optimal performance of these goal-directed behaviours. Here, we tested the hypothesis that histamine neurons under the command of the infralimbic cortex are important to provide behavioural activation. Extracellular histamine and serotonin were measured by microdialysis of the medial prefrontal cortex in behaving rats in parallel with a picrotoxin microinjection into the infralimbic cortex. The injection aroused the rats behaviourally, increased histamine release and decreased serotonin levels. Inhibition of the infralimbic cortex with muscimol produced the opposite effects on neurotransmitter release. The behavioural activation induced by motivating hungry rats with caged food was paralleled by an immediate histamine release, whereas awakening induced by tapping their microdialysis bowl increased serotonin, but not histamine levels. In conclusion, picrotoxin injection into the infralimbic cortex produces behavioural activation together with histamine release; in a similar manner, induction of an appetitive state produced histamine release, likely related to increased behavioural activation characteristic of an appetitive behaviour.

  15. Histamine-releasing activity and bronchoconstricting effects of sisal

    PubMed Central

    Nicholls, P. J.; Evans, Elizabeth; Valić, F.; Žuškin, Eugenija

    1973-01-01

    Nicholls, P. J., Evans, E., Valić, F., and Žuškin, E. (1973).British Journal of Industrial Medicine,30, 142-145. Histamine-releasing activity and bronchoconstricting effects of sisal. Extracts of dry and oiled sisal released histamine from pig and human but not from rat lung tissue. A suspension in Tyrode solution of the oil used for softening the sisal fibres had a pH of 8·1 and also released histamine from pig and human lung. The releasing activity was abolished when the pH of this suspension was adjusted to pH 7·4. As all the sisal extracts were adjusted to pH 7·4 for incubation with lung tissue, the histamine-releasing activity of sisal in vitro is unrelated to the presence of the oil. Significant (P < 0·01) mean reductions over the work shift of ventilatory capacity (PEF and FEV1·0) were recorded in all the workers exposed to airborne sisal dust. These reductions were greater in combers than in drawers and spinners. Sisal collected from combing machines possessed more histamine-releasing activity than material from drawing and spinning machines. These results indicate that histamine release by sisal may be the cause of acute ventilatory capacity changes in sisal exposure. PMID:4122162

  16. Histamine release by Western red cedar (Thuja plicata) from lung tissue in vitro

    PubMed Central

    Evans, Elizabeth; Nicholls, P. J.

    1974-01-01

    Evans, Elizabeth and Nicholls, P. J. (1974).British Journal of Industrial Medicine,31, 28-30. Histamine release by Western red cedar(Thuja plicata)from lung tissue in vitro. Various respiratory symptoms have previously been observed in workers exposed to dust from Western red cedar (Thuja plicata). Although an allergic basis for these effects has been proposed, the possibility that the dust may contain a pharmacologically active agent was investigated. Aqueous extracts of two samples of red cedar released significant amounts of histamine from pig and human lung in vitro. For one of these samples, using pig lung, a dose-response relation was found over a narrow range of concentrations. These dusts possessed the same order of histamine-releasing activity as a sample of cotton dust. Potassium cyanide reduced the release of histamine caused by low concentrations of Western red cedar. Similar effects of cyanide on the histamine-releasing activity of cotton dust and compound 48/80 were observed. It is possible that release of histamine in the lungs and upper respiratory tract occurs on inhalation of dust from Western red cedar and this may be a contributory factor to the development of respiratory symptoms in workers exposed to the dust of this wood. PMID:4132384

  17. The mechanism of basophil histamine release in patients with periodontal disease.

    PubMed Central

    Olsson-Wennström, A; Wennström, J L; Mergenhagen, S E; Siraganian, R P

    1978-01-01

    Histamine release from washed peripheral blood basophils of thirty-three subjects with varying degrees of periodontal disease was studied. Dental plaque, serum and basophil leucocytes were collected from individual patients. There was no histamine release when autologous, washed sonicated plaque was added to leucocytes. However, the incubation of autologous plaque with serum at 37 degrees C for 30 min generated a factor which induced histamine release from basophils. This serum factor was stable to heat (56 degrees C, 30 min), eluted from a Sephadex G-100 column at a volume corresponding to a molecular weight of approximately 16,000 daltons and its action was inhibited by antibody to C5. This factor, therefore, is probably C5a. There was a variation in the degree of histamine release seen with the leucocytes of different donors. This variability was a property of the basophil rather than a function of the serum. Basophils from patients with gingival indices of 0.5 to 1.0 had significantly more histamine release than basophils from patients with gingival indices of less than 0.5 or greater than 1.5 (P less than 0.001). These experiments demonstrate that dental plaque activates serum to form C5a which in turn releases histamine from basophils. However, these experiments do not indicate a role for IgE in this reaction since the direct interaction of plaque with basophils did not cause histamine release. The release of mediators from mast cells could play an important role in the induction of the inflammatory response in periodontal disease. PMID:81729

  18. Protection against malaria in mice is induced by blood stage–arresting histamine-releasing factor (HRF)–deficient parasites

    PubMed Central

    Smith, Leanna; Peronet, Roger; Commere, Pierre-Henri; Apetoh, Lionel

    2016-01-01

    Although most vaccines against blood stage malaria in development today use subunit preparations, live attenuated parasites confer significantly broader and more lasting protection. In recent years, Plasmodium genetically attenuated parasites (GAPs) have been generated in rodent models that cause self-resolving blood stage infections and induce strong protection. All such GAPs generated so far bear mutations in housekeeping genes important for parasite development in red blood cells. In this study, using a Plasmodium berghei model compatible with tracking anti–blood stage immune responses over time, we report a novel blood stage GAP that lacks a secreted factor related to histamine-releasing factor (HRF). Lack of HRF causes an IL-6 increase, which boosts T and B cell responses to resolve infection and leave a cross-stage, cross-species, and lasting immunity. Mutant-induced protection involves a combination of antiparasite IgG2c antibodies and FcγR+ CD11b+ cell phagocytes, especially neutrophils, which are sufficient to confer protection. This immune-boosting GAP highlights an important role of opsonized parasite-mediated phagocytosis, which may be central to protection induced by all self-resolving blood stage GAP infections. PMID:27432939

  19. Blood histamine release: A new allergy blood test

    SciTech Connect

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

    1985-05-01

    Allergen-mediated histamine release from human leukocytes represents an important model for in vitro studies of allergic reactions. The purpose of this study was to determine whether the measurement of histamine released in allergic patients (pts) by radioenzymatic assay following mixing of their blood with common allergens represents a reliable index for diagnosis of atopic allergy. Three categories of allergies were used: (1) housedust and mite; (2) cat and dog dander; (3) trees and grasses and ragweed mixture. The presence of allergy was established by intradermal skin testing in the study group of 82 pts. Significant atopy was defined as greater than or equal to 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 less than or equal to 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 greater than or equal to 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.

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

    PubMed

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

    1987-04-01

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

  1. Histamine-releasing factor/translationally controlled tumor protein plays a role in induced cell adhesion, apoptosis resistance and chemoresistance in non-Hodgkin lymphomas.

    PubMed

    He, Song; Huang, Yuejiao; Wang, Yuchan; Tang, Jie; Song, Yan; Yu, Xiafei; Ma, Jing; Wang, Shitao; Yin, Haibing; Li, Qiuyue; Ji, Lili; Xu, Xiaohong

    2015-07-01

    Mounting evidence has proved that cellular adhesion confers resistance to chemotherapy in multiple lymphomas. The molecular mechanism underlying cell adhesion-mediated drug resistance (CAM-DR) is, however, poorly understood. In this study, we investigated the expression and biologic function of histamine-releasing factor (HRF) in non-Hodgkin lymphomas (NHLs). Clinically, by immunohistochemistry analysis we observed obvious up-regulation of HRF in NHLs including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and natural killer (NK)/T-cell lymphoma. Functionally, overexpression and knockdown of HRF demonstrated the antiapoptotic effect of HRF in NHL cells, which may be associated with activation of the p-CREB/BCL-2 signaling pathway. Moreover, cell adhesion assay demonstrated that adhesion to fibronectin (FN) or HS-5 up-regulated HRF expression, while knockdown of HRF resulted in decreased cell adhesion, which led to reversed CAM-DR. Our finding supports the role of HRF in NHL cell apoptosis, adhesion and drug resistance, and may provide a clinical therapeutic target for CAM-DR in NHL.

  2. Histamine release from human buffy coat-derived mast cells.

    PubMed

    Wang, Xian Song; Lau, Hang Yung Alaster

    2007-04-01

    Mast cells are unique immune cells that release a spectrum of chemical mediators contributing to the inflammatory symptoms of allergic disorders. Although mast cell biology has been extensively studied in the rodents, research on human mast cells is hampered by the lack of a convenient preparation source. This problem has now been addressed by culturing human mast cells from CD34(+) progenitors. We have recently discovered that human buffy coat preparations from local blood banks are an abundant and convenient source of progenitors for culturing mature mast cells which express functional high affinity IgE receptors and contain histamine and tryptase in their granules. In the current study, we further characterize these buffy coat-derived mast cells by studying their responses to common mast cell secretagogues and stabilizers. Mature human mast cells were obtained by culturing isolated progenitors in methylcellulose containing stem cell factor (SCF), IL-3 and IL-6 for 6 weeks and subsequently in liquid medium containing SCF and IL-6 for another 6 to 8 weeks. Following sensitisation with human IgE, these cells released histamine dose-dependently upon activation by anti-IgE and calcium ionophores while compound 48/80 and substance P were relatively ineffective. When the effects of anti-asthmatic agents on anti-IgE-induced mediator release from these cells were compared, only the beta(2)-adrenoceptor agonists and phosphodiesterase inhibitors produced dose-dependent inhibition but not cromolyn or nedocromil. In total, mast cells cultured from human buffy coat progenitors shared similar functional properties of MC(T) subtype of mast cells found predominantly in human lung parenchyma and intestinal mucosa.

  3. The fate of released histamine: reception, response and termination.

    PubMed Central

    Rangachari, P. K.

    1998-01-01

    Histamine released from ECL cells elicits responses from a variety of cellular targets in the vicinity. Three sets of receptors are involved (H1, H2 and H3). Receptor occupation is promptly transduced into cellular responses. The responses, in turn, are terminated by diverse mechanisms: enzymatic inactivation, cellular uptake and desensitization at the receptor level. Under specific pathological conditions, histamine effects could be exaggerated by the presence of derivatives that may be of marginal relevance under physiological conditions. Images Figure 2 PMID:10461350

  4. Caffeine promotes glutamate and histamine release in the posterior hypothalamus

    PubMed Central

    Kodama, Tohru; Siegel, Jerome M.

    2014-01-01

    Histamine neurons are active during waking and largely inactive during sleep, with minimal activity during rapid-eye movement (REM) sleep. Caffeine, the most widely used stimulant, causes a significant increase of sleep onset latency in rats and humans. We hypothesized that caffeine increases glutamate release in the posterior hypothalamus (PH) and produces increased activity of wake-active histamine neurons. Using in vivo microdialysis, we collected samples from the PH after caffeine administration in freely behaving rats. HPLC analysis and biosensor measurements showed a significant increase in glutamate levels beginning 30 min after caffeine administration. Glutamate levels remained elevated for at least 140 min. GABA levels did not significantly change over the same time period. Histamine level significantly increased beginning 30 min after caffeine administration and remained elevated for at least 140 min. Immunostaining showed a significantly elevated number of c-Fos-labeled histamine neurons in caffeine-treated rats compared with saline-treated animals. We conclude that increased glutamate levels in the PH activate histamine neurons and contribute to caffeine-induced waking and alertness. PMID:25031227

  5. Caffeine promotes glutamate and histamine release in the posterior hypothalamus.

    PubMed

    John, Joshi; Kodama, Tohru; Siegel, Jerome M

    2014-09-15

    Histamine neurons are active during waking and largely inactive during sleep, with minimal activity during rapid-eye movement (REM) sleep. Caffeine, the most widely used stimulant, causes a significant increase of sleep onset latency in rats and humans. We hypothesized that caffeine increases glutamate release in the posterior hypothalamus (PH) and produces increased activity of wake-active histamine neurons. Using in vivo microdialysis, we collected samples from the PH after caffeine administration in freely behaving rats. HPLC analysis and biosensor measurements showed a significant increase in glutamate levels beginning 30 min after caffeine administration. Glutamate levels remained elevated for at least 140 min. GABA levels did not significantly change over the same time period. Histamine level significantly increased beginning 30 min after caffeine administration and remained elevated for at least 140 min. Immunostaining showed a significantly elevated number of c-Fos-labeled histamine neurons in caffeine-treated rats compared with saline-treated animals. We conclude that increased glutamate levels in the PH activate histamine neurons and contribute to caffeine-induced waking and alertness.

  6. The influences of adrenolytic drugs and noradrenaline on the histamine release in cardiac anaphylaxis in vitro

    PubMed Central

    Giotti, A.; Guidotti, A.; Mannaioni, P. F.; Zilletti, Lucilla

    1966-01-01

    1. The regional distribution (auricles, ventricles and septum) of histamine and its release during anaphylaxis were studied in isolated perfused guinea-pig hearts. 2. The highest value of histamine content was found in the right auricle, the lowest in the left ventricle and septum, both in normal hearts, and in the hearts subjected to anaphylaxis. 3. The fraction of the total histamine released in the course of 24 min by antigen was 50%. The fraction released from the different regions of the heart was similar. No evidence was found for release of 5-hydroxytryptamine. 4. A relation was found between the distribution of mast cells and the tissue concentration of histamine. The highest number of mast cells per unit area was found in the right auricle; the lowest in the left ventricle. 5. The histamine release by antigen was reduced by previous treatment with (+)-tubocurarine; the histamine release by (+)-tubocurarine was depressed by previous challenge of the heart with antigen. 6. Reserpine reduces histamine release. Perfusion of reserpine-treated hearts with noradrenaline partially restored histamine release. 7. β-Adrenergic blocking agents (dichloroisoproterenol and pronethalol) reduced histamine release. 8. The drugs tested did not modify the tissue concentration of histamine. 9. The possibility of a modulating activity of catecholamines on histamine release in cardiac anaphylaxis is discussed. PMID:4380397

  7. Release of histamine from mast cells by a synthetic ionophore

    SciTech Connect

    Atkinson, T.P.; Smith, T.F.; Hunter, R.L.

    1986-03-01

    Polyphore 27:10 is a copolymer composed of blocks of polyoxyethylene and polyoxypropylene. Subcutaneous injection of this copolymer in mice causes significant inflammation as determined by footpad swelling and increased vascular permeability as measured by extravasation of Evan's blue dye. Micromolar concentrations trigger release of histamine from purified mouse mast cells and human peripheral blood basophils in vitro. Histamine release from murine mast cells required physiologic temperature, metabolic energy, and calcium ions in the surrounding medium. Replacement of sodium ions in the medium with either potassium or lithium markedly inhibited release. Since Polyphore 27:10 has structural homology with ethylenediamine tetraacetic acid (EDTA) and the crown polyethers, both of which chelate metal ions, The authors investigated whether Polyphore 27:10 could act as an ionophore. The Polyphore transported cations across artificial lipid membranes and made erythrocytes highly permeable to sodium ions, but not calcium at physiologic concentrations. They propose that the potent inflammatory and histamine-releasing activities of this copolymer are in part due to its ability to depolarize and degranulate mast cells.

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

    PubMed

    Baldo, B A; Pham, N H

    2012-03-01

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

  9. Agarwood Inhibits Histamine Release from Rat Mast Cells and Reduces Scratching Behavior in Mice: Effect of Agarwood on Histamine Release and Scratching Behavior.

    PubMed

    Inoue, Eiji; Shimizu, Yasuharu; Masui, Ryo; Tsubonoya, Tomoe; Hayakawa, Tomomi; Sudoh, Keiichi

    2016-09-01

    This study was conducted to clarify the effects of agarwood on histamine release from mast cells in rats and on the scratching behaviors in mice. Histamine release from rat mast cells induced by compound 48/80 or concanavalin A (Con A) and compound 48/80-induced scratching behavior in mice were examined to investigate the effects of agarwood. The hyaluronidase activity and the 3',5'-cyclic adenosine monophosphate (cAMP) levels in mast cells were examined to investigate the mechanisms for the inhibition of histamine release. The correlation between the inhibitory effects of agarwood on histamine release and the content of its typical ingredients, a 2-(2-phenylethyl)chromone derivatives, was analyzed using thin-layer chromatography. Agarwood showed an inhibitory effect on mast-cell histamine release induced by compound 48/80 or Con A without any effect on hyaluronidase activity; this effect involves an increase in the cAMP levels in mast cells. Oral administration of agarwood showed an inhibitory effect on compound 48/80-induced scratching behavior in mice. The inhibitory effects of agarwood on histamine release were quite different, depending on the area where the agarwood was produced, its quality, and its market price. No correlation was found between the inhibitory effects of agarwood on histamine release and the typical ingredients of agarwood, which are 2-(2-phenylethyl)chromone derivatives. These results show that agarwood inhibits histamine release from mast cells partially through an increase in the cAMP levels in cells. We suggest that some active ingredients of agarwood must be effective on oral intake and that agarwood can be used to treat patients with a number of conditions, including urticaria, atopic dermatitis, and bronchial asthma, in which an increase in histamine release occurs. Differences in the pharmacological effects of this crude drug among markets may provide important information for the quality control of this herbal medicine.

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

    SciTech Connect

    Poli, E.; Coruzzi, G.; Bertaccini, G. )

    1991-01-01

    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 ({sup 3}H)choline. In the presence of H1 and H2 blockade, histamine and (R)-{alpha}-methylhistamine inhibited the electrically-evoked acetylcholine release, being (R)-{alpha}-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)-{alpha}-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.

  11. Histamine release inhibitory activity of Piper nigrum leaf.

    PubMed

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

    2008-10-01

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

  12. In vitro evaluation of the potential role of sulfite radical in morphine-associated histamine release

    PubMed Central

    Gordon, Emma M; Myers, Carolyn; Blumer, Jeffrey

    2004-01-01

    Background Intravenous morphine use is associated with elevated histamine release leading to bronchoconstriction, edema and hemodynamic instability in some patients. This study evaluated the possibility that sulfite, which is present as a preservative in many morphine preparations, might contribute to histamine release in vitro. Results The human mast cell line, HMC-1, was exposed to various morphine concentrations, in the absence of sulfite, under cell culture conditions. Clinically attained concentrations of morphine (0.018μg/ml and 0.45μg/ml) did not cause increased histamine release from mast cells. There was a significant increase in histamine release when the morphine concentration was increased by 1184-fold (668μg/ml morphine). Histamine release from mast cells exposed to morphine and/or sulfite required the presence of prostaglandin H synthetase. Histamine release in experiments using sulfite-containing morphine solutions was not statistically different from that observed in morphine-only solutions. Conclusion Sulfite in sulfite-containing morphine solutions, at concentrations seen clinically, is not responsible for histamine release in in vitro experiments of the human mast cell line, HMC-1. This does not preclude the fact that sulfite may lead to elevation of histamine levels in vivo. PMID:15469613

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

    PubMed

    Schlicker, E; Werthwein, S; Zentner, J

    1999-01-01

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

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

    SciTech Connect

    Noah, T.L.; Paradiso, A.M.; Madden, M.C.; McKinnon, K.P.; Devlin, R.B. )

    1991-11-01

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

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

    PubMed

    Ishizuka, Tomoko; Yamamoto, Yumiko; Yamatodani, Atsushi

    2002-04-26

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

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

    PubMed

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

    2007-11-01

    Environmental perfume exposure may cause respiratory symptoms. Individuals with asthma and perfume contact allergy report such symptoms more frequently than others. However, immunologic mechanisms have not been demonstrated and the symptoms are not associated with IgE-mediated allergy. The study aimed to investigate whether basophils from patients with respiratory symptoms related to perfume released more histamine in the presence of perfume as compared with healthy volunteers. Histamine release was measured by the glass fibre method. Blood was obtained from healthy volunteers (n=20) and patients with respiratory symptoms related to perfume (n=17) attending a dermatological outpatient clinic for patch testing. The effect of an international brand perfume was investigated using the basophil histamine release test with perfume. Furthermore, basophils from a healthy non-atopic donor were incubated with participant's sera and histamine release induced by perfume was measured. In both groups incremental perfume concentrations showed a positive and significant (P<0.001) dose-response effect on the release of histamine. At the highest perfume concentration, the basophils released significantly (P<0.05) more histamine in patients as compared with healthy volunteers. No difference was found between the groups when sera were incubated with basophils from a healthy non-atopic donor. Perfume induces a dose-dependent non-IgE-mediated release of histamine from human peripheral blood basophils. Increased basophil reactivity to perfume was found in patients with respiratory symptoms related to perfume.

  17. Agarwood Inhibits Histamine Release from Rat Mast Cells and Reduces Scratching Behavior in Mice

    PubMed Central

    Inoue, Eiji; Shimizu, Yasuharu; Masui, Ryo; Tsubonoya, Tomoe; Hayakawa, Tomomi; Sudoh, Keiichi

    2016-01-01

    Objectives: This study was conducted to clarify the effects of agarwood on histamine release from mast cells in rats and on the scratching behaviors in mice. Methods: Histamine release from rat mast cells induced by compound 48/80 or concanavalin A (Con A) and compound 48/80-induced scratching behavior in mice were examined to investigate the effects of agarwood. The hyaluronidase activity and the 3’,5’-cyclic adenosine monophosphate (cAMP) levels in mast cells were examined to investigate the mechanisms for the inhibition of histamine release. The correlation between the inhibitory effects of agarwood on histamine release and the content of its typical ingredients, a 2-(2-phenylethyl)chromone derivatives, was analyzed using thin-layer chromatography. Results: Agarwood showed an inhibitory effect on mast-cell histamine release induced by compound 48/80 or Con A without any effect on hyaluronidase activity; this effect involves an increase in the cAMP levels in mast cells. Oral administration of agarwood showed an inhibitory effect on compound 48/80-induced scratching behavior in mice. The inhibitory effects of agarwood on histamine release were quite different, depending on the area where the agarwood was produced, its quality, and its market price. No correlation was found between the inhibitory effects of agarwood on histamine release and the typical ingredients of agarwood, which are 2-(2-phenylethyl)chromone derivatives. Conclusion: These results show that agarwood inhibits histamine release from mast cells partially through an increase in the cAMP levels in cells. We suggest that some active ingredients of agarwood must be effective on oral intake and that agarwood can be used to treat patients with a number of conditions, including urticaria, atopic dermatitis, and bronchial asthma, in which an increase in histamine release occurs. Differences in the pharmacological effects of this crude drug among markets may provide important information for the quality

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

    PubMed Central

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

    1988-01-01

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

  19. Acute central administration of immepip, a histamine H3 receptor agonist, suppresses hypothalamic histamine release and elicits feeding behavior in rats.

    PubMed

    Chiba, Seiichi; Itateyama, Emi; Sakata, Toshiie; Yoshimatsu, Hironobu

    2009-04-06

    Histamine suppresses feeding behavior via histamine H1 receptors in the hypothalamus. This study was performed to examine whether the acute reduction of histamine release in the hypothalamus caused by immepip, a histamine H3 agonist, modulates the feeding behavior of rats. Rats had a catheter implanted in the third cerebral ventricle (i3v) and were given central injections of phosphate-buffered-saline or immepip (100-300 pmol/rat). Following the i3v administration of immepip, the rats developed dose-dependent hypokinesia within 10 min of administration. Next to hypokinesia, the rats showed significant dose-dependent feeding behavior. High-performance liquid chromatography (HPLC) confirmed the reduction in histamine release in the hypothalamus of rats following i3v administration of immepip. These results suggest that i3v administration of immepip, an H3 receptor agonist, suppresses hypothalamic histamine release and elicits feeding behavior in rats.

  20. The effect of ethanol, beer, and wine on histamine release from the dog stomach.

    PubMed

    Intorre, L; Bertini, S; Luchetti, E; Mengozzi, G; Crema, F; Soldani, G

    1996-01-01

    The mediator for the action of ethanol on the parietal cell of the stomach is not known. However, because the action of ethanol on gastric acid secretion was proposed to involve the release of histamine, we decided to investigate the effects of ethanol and some alcoholic beverages (red wine and beer) on histamine release from the dog stomach. After performing a splenectomy in anaesthetized beagle dogs, the gastrosplenic vein draining the corpus of the stomach was cannulated for blood withdrawal to evaluate the local release of gastrin and histamine by RIA. Intragastric administration of 200 ml of beer (4.8% ethanol) or red wine (12.5% ethanol) caused a significant enhancement in gastrin and histamine concentrations in venous blood from the stomach. By contrast, intragastric administration of pure ethanol in distilled water at the same concentrations of wine or beer did not significantly modify gastrin and histamine release. Integrated histamine responses for 20 min to beer and wine paralleled gastrin concentrations and were of the same magnitude of those induced by intravenous infusion of pentagastrin at 1 and 6 micrograms/ kg/h, respectively. We conclude that: 1) beer and red wine, but not pure ethanol, are potent releasers of histamine; 2) histamine release seems to be related to the gastrin response and probably occurs at the level of enterochromaffin-like (ECL) cells; 3) the ethanol content of these drinks is not important for their stimulant effect, indicating that some other components of beer and wine are responsible for gastrin and histamine release from the dog stomach.

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

    PubMed Central

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

    1996-01-01

    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 immepip (0.01-10 microM) mimicked the effect of histamine. 3. Neither 2-thiazolylethylamine (TEA), an agonist showing some selectivity for H1 receptors, nor the H2 receptor agonist, dimaprit, modified 100 mM K(+)-evoked release of acetylcholine. 4. The inhibitory effect of 100 microM histamine was completely prevented by the highly selective histamine H3 receptor antagonist, clobenpropit but was resistant to antagonism by triprolidine and cimetidine, antagonists at histamine H1 and H2 but not H3 receptors. 5. The H3 receptor-induced inhibition of K(+)-evoked release of acetylcholine was fully sensitive to tetrodotoxin (TTX). 6. The effects of intraperitoneal (i.p.) injection of imetit (5 mg kg-1) and RAMH (5 mg kg-1) were tested on acetylcholine release and short term memory paradigms. Both drugs reduced 100 mM K(+)-evoked release of cortical acetylcholine, and impaired object recognition and a passive avoidance response. 7. These observations provide the first evidence of a regulatory role of histamine H3 receptors on cortical acetylcholine release in vivo. Moreover, they suggest a role for histamine in learning and memory and may have implications for the treatment of degenerative disorders associated with impaired cholinergic function. PMID:8982515

  2. Deuterium-oxide-induced histamine release from basophils of allergic subjects. I. Responsiveness to deuterium oxide requires an activation step

    SciTech Connect

    Kazimierczak, W.; Plaut, M.; Knauer, K.A.; Meier, H.L.; Lichtenstein, L.M.

    1984-04-01

    Basophils from many atopic persons, and especially asthmatic patients, have been shown to release histamine in response to 44% deuterium oxide (D2O), whereas basophils from nonatopic persons do not release histamine. The present experiments analyzed the mechanisms by which D/sub 2/O mediated release. It was found that although D/sub 2/O induced release from washed leukocytes, it failed to induce release from whole blood or from leukocytes that had sedimented but had not been washed. The kinetics of release after washing were rapid and were equivalent regardless of the temperature at which cells were sedimented (O degrees or 37 degrees C). Washed cells became desensitized to the action of D/sub 2/O within 30 to 60 min at 37 degrees C, whereas unwashed leukocytes did not become desensitized. Serum or plasma inhibited D/sub 2/O-induced release, although high concentrations (1/5) were less inhibitory than lower ones (1/10 to 1/100). Basophils from D/sub 2/O responders also released histamine in response to a ''platelet enhancing factor'' (PEF), whereas those from D/sub 2/O nonresponders did not. As with D/sub 2/O-mediated release, PEF-mediated release occurred only with washed leukocytes, desensitized within 30 to 60 min at 37 degrees C, and was inhibited by serum. These results suggest that D/sub 2/O induces histamine release by augmenting the effects of an endogenous activation mechanism, and that PEF acts on the same (D/sub 2/O-responsive) donors to augment this activation mechanism. Cell activation, as well as desensitization of this activation mechanism, occurs rapidly when basophils are washed free of plasma inhibitors and placed at 37 degrees C.

  3. Enhanced histamine release from lung mast cells of guinea pigs exposed to sulfuric acid aerosols

    SciTech Connect

    Fujimaki, Hidekazu ); Katayama, Noboru; Wakamori, Kazuo )

    1992-06-01

    To clarify the relationship between air pollution and mast cell response, the effects of sulfuric acid aerosols on histamine release from lung mast cells of guinea pigs were investigated. Guinea pigs were exposed to 0.3, 1.0 and 3.2 mg/m{sup 3} sulfuric acid (H{sub 2}SO{sub 4}) aerosols or 4 ppm nitrogen dioxide (NO{sub 2}) for 2 and 4 weeks. After the exposure, lung mast cell suspensions were isolated by collagenase treatment and antigen- or A23187-induced histamine release was measured. Antigen-induced histamine release from mast cells was significantly enhanced by the exposure to 1.0 and 3.2 mg/m{sup 3} H{sub 2}SO{sub 4} for 2 weeks, but exposure to H{sub 2}SO{sub 4} for 4 weeks did not show the enhancement of antigen-induced histamine release. A23187-induced histamine release was significantly enhanced by the exposure to 1.0 mg/m{sup 3} H{sub 2}SO{sub 4} or 4 ppm NO{sub 2} for 2 weeks, but suppression of histamine release from lung mast cells stimulated with A23187 was observed by the exposure to 3.2 mg/m{sup 3} H{sub 2}So{sub 4} for 4 weeks. The exposure to 0.3 mg/m{sup 3} H{sub 2}So{sub 4} showed no changes in antigen- and A23187-induced histamine release. The combination of 1.0 mg/m{sup 3} H{sub 2}So{sub 4} with 4 ppm NO{sub 2} for 2 weeks resulted in no changes in antigen- and A23187-induced histamine release. These results suggested that functional properties of lung mast cells may be altered by a low concentration of H{sub 2}So{sub 4} aerosol exposure.

  4. Carnosine attenuates mast cell degranulation and histamine release induced by oxygen-glucose deprivation.

    PubMed

    Shen, Yao; Zhang, Shihong; Fu, Lin; Hu, Weiwei; Chen, Zhong

    2008-04-01

    Carnosine (beta-alanyl-histidine) is a naturally occurring dipeptide that has been characterized as a putative hydrophilic antioxidant. The protective function of carnosine has been demonstrated in neuronal cells under ischemic injury. The purpose of this study was to investigate the effects of carnosine on oxygen-glucose deprivation (OGD)-induced degranulation and histamine release from mast cells. Cultured mast cells were exposed to OGD for 4 h, and then the degranulation was observed immediately by microscopy. Histamine release was analyzed by high-performance liquid chromatography (HPLC). OGD caused degranulation of mast cells, and increased histamine and lactate dehydrogenase (LDH) release. Carnosine (at a concentration of 5 mM) alone did not produce any appreciable effect on degranulation, histamine, and LDH release from mast cells under normal condition, but significantly inhibited the degranulation, histamine, and LDH release of mast cells induced by OGD. These results indicate that carnosine can protect mast cells from degranulation and histamine release and it may be an endogenous mast cell stabilizer in the pathological processes induced by ischemia.

  5. Modulation of histamine release from human basophils in vitro by physiological concentrations of zinc

    SciTech Connect

    Marone, G.; Findlay, S.R.; Lichtenstein, L.M.

    1981-05-01

    Zinc, at physiologic concentrations, inhibits in vitro histamine release from human basophils induced by several immunologic (i.e., antigen and anti-immunoglobulin E (IgE) and nonimmunologic (Ca/sup + +/ ionophore A23187 and formylated tripeptide formyl-methionyl-leucyl-phenylalanine (f-met peptide)) stimuli in a dose-dependent manner. Inhibition begins at about 10(-6) (ionophore A23187, anti-IgE and antigen) or 10(-5) M (f-met peptide) and is maximum at 10(-4) M (80--100% inhibition of histamine release). The activity of zinc is about 25-fold greater with respect to ionophore A23187 (ID50 . 1.1 x 10(-6) M) than to f-met peptide-induced (ID50 . 4 x 10(-5) M) histamine release. Its activity on IgE-mediated histamine release is intermediate between these two extremes (ID50 . 9.7 x 10(-6) M). Zinc does not affect the first stage of histamine release but acts on the calcium-dependent second stage. It is a competitive antagonist of the action of Ca/sup + +/ in histamine secretion induced by antigen, anti-IgE and f-met peptide (but not by A23187) with a dissociation constant of about 1.2 x 10(-5) M. The addition of colchicine with zinc fails to increase the inhibition caused by the ion alone, suggesting the two compounds work via a common mechanism of action. Deuterium oxide reversed, in a dose-dependent manner, the inhibition of histamine release caused by zinc. These results suggest that the effect of zinc on histamine release from human basophils may be related to its influence on the microtubule system, directly or via its interaction with calcium.

  6. Histamine release in the basal forebrain mediates cortical activation through cholinergic neurons.

    PubMed

    Zant, Janneke C; Rozov, Stanislav; Wigren, Henna-Kaisa; Panula, Pertti; Porkka-Heiskanen, Tarja

    2012-09-19

    The basal forebrain (BF) is a key structure in regulating both cortical activity and sleep homeostasis. It receives input from all ascending arousal systems and is particularly highly innervated by histaminergic neurons. Previous studies clearly point to a role for histamine as a wake-promoting substance in the BF. We used in vivo microdialysis and pharmacological treatments in rats to study which electroencephalogram (EEG) spectral properties are associated with histamine-induced wakefulness and whether this wakefulness is followed by increased sleep and increased EEG delta power during sleep. We also investigated which BF neurons mediate histamine-induced cortical activation. Extracellular BF histamine levels rose immediately and remained constant throughout a 6 h period of sleep deprivation, returning to baseline levels immediately afterward. During the spontaneous sleep-wake cycle, we observed a strong correlation between wakefulness and extracellular histamine concentrations in the BF, which was unaffected by the time of day. The perfusion of histamine into the BF increased wakefulness and cortical activity without inducing recovery sleep. The perfusion of a histamine receptor 1 antagonist into the BF decreased both wakefulness and cortical activity. Lesioning the BF cholinergic neurons abolished these effects. Together, these results show that activation of the cholinergic BF by histamine is important in sustaining a high level of cortical activation, and that a lack of activation of the cholinergic BF by histamine may be important in initiating and maintaining nonrapid eye movement sleep. The level of histamine release is tightly connected to behavioral state, but conveys no information about sleep pressure.

  7. Modulation of neurotransmitter release via histamine H3 heteroreceptors.

    PubMed

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

    1994-01-01

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

  8. Cyclic AMP agonist inhibition increases at low levels of histamine release from human basophils

    SciTech Connect

    Tung, R.S.; Lichtenstein, L.M.

    1981-09-01

    The relationship between the intensity of the signal for antigen-induced immunoglobulin E-mediated histamine release from human basophils and the concentration of agonist needed to inhibit release has been determined. The agonists, prostaglandin E1, dimaprit, fenoterol, isobutylmethylxanthine and dibutyryl cyclic AMP, all act by increasing the cyclic AMP level. Each agonist was 10- to 1000-fold more potent (relative ID50) at low levels of histamine release (5-10% of total histamine) than at high levels (50-80%). Thus, the inhibitory potential of a drug is a function of the concentration of antigen used to initiate the response. Our results are now more in accord with the inhibitory profile of these drugs in human lung tissue. It is suggested that in vivo release is likely to be low and that this is the level at which to evaluate drugs in vitro.

  9. Effect of disodium cromoglycate on antigen-evoked histamine release from human skin

    PubMed Central

    Pearce, Cheryl A.; Greaves, M. W.; Plummer, Valerie M.; Yamamoto, S.

    1974-01-01

    The effect of disodium cromoglycate (DSCG) on antigen-evoked histamine release from IgE-sensitized human skin in vitro has been studied using breast skin from six donors. Concentrations of DSCG ranging from 10–200 μM did not produce any consistent effect on histamine release, the results ranging from moderate inhibition to moderate enhancement. With higher concentrations of DSCG (400–500 μM) enhancement of release occurred in nearly all experiments. Variation of antigen concentration did not modify the response to DSCG. These results do not support the possibility that DSCG may be effective in the treatment of immediate hypersensitivity reactions in human skin. PMID:4143251

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

    PubMed

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

    2010-02-08

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

  11. Model of cell activation and desensitization by surface immunoglobin: the case of histamine release from human basophils

    SciTech Connect

    Dembo, M.; Goldstein, B.

    1980-11-01

    We present a model for the control of immunoglobulin E (IgE)-mediated histamine release from human basophils. We suggest that there is a calcium gating factor which interacts with crosslinked IgE to form a short-lived open calcium channel. After formation of the channel the activated gating factor rapidly decays to an inactive form. It is the loss of the active gating factor which causes the basophil to desensitize nonspecifically. We propose that the crosslinked IgE molecules are deactivated by a mechanism, such as endocytosis or shedding, which is independent of the mechanism which inactivates the calcium gating factor. This loss of functional IgE leads to specific desensitization. The mathematical formulation of the model explains the relationship of specific and nonspecific desensitization to the amount of specific IgE on the basophil surface; explains why there are two types of antigen excess inhibition; explains the relationship between antigen excess inhibition and desensitization; explains why, for a fixed antigen concentration, increasing the concentration of cell surface IgE increases histamine release until an optimal concentration is reached, then decreases histamine release; predicts the effects that changing the external calcium will have on the dose response curve; and predicts that increasing the amount of specific IgE on the cell surface will cause the dose response curve to undergo a transition from a curve with a single maximum to a curve with two maxima.

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

    PubMed

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

    2008-12-15

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

  13. Alpha 2-adrenoceptor-mediated inhibition of histamine release from rat cerebral cortical slices.

    PubMed

    Hill, S J; Straw, R M

    1988-12-01

    1. Depolarization of rat cerebral cortical slices, prelabelled with [3H]-histidine, in high potassium (40 mM KCl) medium stimulated the release of [3H]-histamine. The K+-evoked release of [3H]-histamine was attenuated by incubation in calcium-free medium and prevented by prior incubation of brain slices with the selective histidine decarboxylase inhibitor S-(alpha)-fluoromethylhistidine. 2. The K+-evoked release of [3H]-histamine was significantly (P less than 0.001) reduced following stimulation of histamine H3-receptors with R-(alpha)-methylhistamine (1 microM) and this effect was antagonized by the H3-antagonist thioperamide (1 microM). 3. Noradrenaline and the alpha 2-selective adrenoceptor agonists clonidine and UK-14,304 inhibited the K+-evoked release of [3H]-histamine in a concentration-dependent manner yielding EC50 values of 2.5, 0.8 and 1.2 microM, respectively. However, the maximum response to clonidine was only 52 +/- 8% of that obtained with noradrenaline. 4. The inhibitory effect of noradrenaline was antagonized by the non-selective alpha-antagonist phentolamine and by the selective alpha 2-antagonists yohimbine and idazoxan. However, the response to noradrenaline was not inhibited by the alpha 1-antagonist prazosin at concentrations up to 1 microM. 5. These results suggest that both histamine H3-receptors and alpha 2-adrenoceptors are present on histamine-containing nerve terminals in rat cerebral cortex and can exert an inhibitory influence on neurotransmitter release.

  14. Analysis of histamine release assays using the Bootstrap.

    PubMed

    Coberly, William A; Price, Joseph A

    2005-01-01

    The data from several types of bioassays is usually presented as a quotient as an intuitive parameter and a means of comparing results between experiments. For the example we considered here, we look at experiments with an experiment-wide negative control used to generate percent activity quotients from each experimental group. We asked if there was a valid means to statistically evaluate the transformed rather than the raw data. The experimental system chosen was a dose response of the agonist compound 48/80, which causes release of histamine from mast cells, thus providing test data from replicates of n=24. Descriptive statistics, the Ryan-Joiner test for normality of distribution of data, and normal probability plots confirm the normality of the distribution of data at each dose level. In parametric analysis, when the control group was treated as an errorless constant, there was a distinct consistent bias in the standard error of the data of 10% or less, which was not present if the control group's mean was treated as a variable with experimental error. This would be of minor interest in qualitative studies and might be safely ignored, but might be of considerable importance in quantitative assessments of activity using confidence intervals. When using Bootstrap estimates of standard error and probability plots of the bootstrap samples, the transformed data does not deviate significantly from normality. The standard, bias-corrected percentile limits (BCa), and empirical percentile methods gave very similar results when using resampling statistics to generate the transformed data from groups of n=6. Sample size can be as low as n=4 and still provide useful results. Thus, we have shown that resampling (i.e., bootstrap, Monte Carlo method, computer-intensive methods) can produce the data transform as well as provide confidence intervals using this type of raw data in small groups (n=4 to 6), giving improved statistical analysis of the transformed data (ratio

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

    PubMed

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

    1993-07-01

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

  16. Human in vivo cutaneous microdialysis: estimation of histamine release in cold urticaria.

    PubMed

    Andersson, T; Wårdell, K; Anderson, C

    1995-09-01

    A novel bioanalytical in vivo sampling technique, cutaneous microdialysis, was used to follow the chronology of skin histamine release in 3 patients with cold urticaria and in 2 healthy volunteers. Laser Doppler perfusion imaging was used simultaneously to monitor the skin circulatory response. Microdialysis samples were collected at 10-min intervals and analysed by radioimmunoassay technique. Fifty minutes after probe insertion, the ventral forearm skin in the area of the dialysis membrane was provoked for 5-15 min with a 25 x 40 mm ice cube covered with plastic foil. In the cold urticaria patients, an up to 80-fold increase of histamine was observed, with peak levels 20-30 min after challenge. Histamine levels then fell to reach "baseline" levels within 50 min. In the healthy subjects, the histamine increase was earlier, less pronounced and of shorter duration. Cutaneous microdialysis and laser Doppler imaging offer new possibilities for the chronological multiparameter assessment of inflammatory skin disorders in vivo.

  17. Histamine release upon adenosine 5'-monophosphate (AMP) nasal provocation in allergic subjects

    PubMed Central

    Polosa, R; Pagano, C; Prosperini, G; Low, J; Dokic, D; Church, M; Crimi, N

    1999-01-01

    BACKGROUND—Nasal provocation with adenosine 5'-monophosphate (AMP) elicits nasal symptoms in subjects with rhinitis. Histamine released from mast cells may play a part in AMP induced nasal responses.
METHODS—Symptoms of rhinitis were recorded and histamine release in the fluid obtained by nasal lavage after AMP, guanosine 5'-monophosphate (GMP), and placebo instillations was measured in nine subjects with allergic rhinitis and nine non-allergic controls in a double blind, randomised, placebo controlled study.
RESULTS—No symptoms or significant increases in histamine were observed after GMP and placebo challenge. Significantly higher levels of histamine were seen in the nasal lavage fluids of allergic subjects following AMP challenge than in non-allergic controls, the median (range) histamine concentration increasing from the baseline value of 1.62 (0.44-6.99) ng/ml to 6.45 (0.81-16.17) ng/ml at three minutes. No increase in histamine levels was seen in the non-allergic subjects in whom the median histamine concentration was 1.13 (0.29-4.25) ng/ml at baseline and 0.97 (0.31-5.89) ng/ml three minutes after AMP challenge.
CONCLUSIONS—AMP elicits an immediate rise in histamine levels in the nasal lavage fluid of allergic subjects compared with non-allergic individuals. These findings indicate that the exaggerated nasal response to adenosine may reflect mast cell priming in vivo, thus supporting its application as a potential new marker of allergic inflammation.

 PMID:10325898

  18. A comparative study on basophil activation test, histamine release assay, and passive sensitization histamine release assay in the diagnosis of peanut allergy.

    PubMed

    Larsen, L F; Juel-Berg, N; Hansen, K S; Clare Mills, E N; van Ree, R; Poulsen, L K; Jensen, B M

    2017-07-07

    Allergy can be diagnosed using basophil tests. Several methods measuring basophil activation are available. This study aimed at comparing basophil activation test (BAT), histamine release assay (HR), and passive sensitization histamine release assay (passive HR) in the diagnosis of peanut allergy. BAT, HR, and passive HR were performed on 11 peanut-allergic and 14 nonallergic subjects. Blood was incubated with peanut extract or anti-IgE and tests were performed as follows: BAT-CD63 upregulation was assessed by flow cytometry; HR-released histamine was quantified by a glass fiber-based fluorometric method; passive HR-IgE-stripped donor basophils were incubated with participants' serum and histamine release was quantified as HR. CDsens, a measure of basophil allergen sensitivity, was significantly higher for BAT (80.1±17.4) compared to HR (23.4±10.31) and passive HR (11.1±2.0). BAT, HR, and passive HR had a clinical sensitivity of 100%, 100%, and 82% and specificity of 100%, 100%, and 100%, respectively, when excluding inconclusive results. BAT identified 11 of 11 allergic patients, HR 10, and passive HR 9. Likewise, BAT recognized 12 of 14 nonallergic subjects, HR 10, and passive HR 13. However, the tests' diagnostic performances were not statistically different. Interestingly, nonreleasers in HR but not in BAT had lower basophil count compared to releasers (249 vs 630 counts/min). BAT displayed a significantly higher CDsens compared to HR and passive HR. The basophil tests' diagnostic performances were not significantly different. Still, BAT could diagnose subjects with low basophil number in contrast to HR. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  19. Anaesthetic agents inhibit gastrin-stimulated but not basal histamine release from rat stomach ECL cells.

    PubMed

    Norlén, P; Kitano, M; Lindström, E; Håkanson, R

    2000-06-01

    By mobilizing histamine in response to gastrin, the ECL cells in the oxyntic mucosa play a key role in the control of the parietal cells and hence of gastric acid secretion. General anaesthesia suppresses basal and gastrin- and histamine-stimulated acid secretion. The present study examines if the effect of anaesthesia on basal and gastrin-stimulated acid secretion is associated with suppressed ECL-cell histamine secretion. A microdialysis probe was implanted in the submucosa of the ventral aspect of the acid-producing part of the stomach (32 rats). Three days later, ECL-cell histamine mobilization was monitored 2 h before and 4 h after the start of intravenous infusion of gastrin (5 nmol kg(-1) h(-1)). The rats were either conscious or anaesthetized. Four commonly used anaesthetic agents were given 1 h before the start of the experiments by intraperitoneal injection: chloral hydrate (300 mg kg(-1)), pentobarbitone (40 mg kg(-1)), urethane (1.5 g kg(-1)) and a mixture of fluanisone/fentanyl/midazolam (15/0.5/7.5 mg kg(-1)). In a parallel series of experiments, basal- and gastrin-induced acid secretion was monitored in six conscious and 25 anaesthetized (see above) chronic gastric fistula rats. All anaesthetic agents lowered gastrin-stimulated acid secretion; also the basal acid output was reduced (fluanisone/fentanyl/midazolam was an exception). Anaesthesia reduced gastrin-stimulated but not basal histamine release by 55 - 80%. The reduction in gastrin-induced acid response (70 - 95%) was strongly correlated to the reduction in gastrin-induced histamine mobilization. The correlation is in line with the view that the reduced acid response to gastrin reflects impaired histamine mobilization. Rat stomach ECL cells were purified by counter-flow elutriation. Gastrin-evoked histamine mobilization from the isolated ECL cells was determined in the absence or presence of anaesthetic agents in the medium. With the exception of urethane, they inhibited gastrin

  20. IGE AND IGGA ANTIBODY-MEDIATED RELEASE OF HISTAMINE FROM RAT PERITONEAL CELLS

    PubMed Central

    Bach, Michael K.; Bloch, Kurt J.; Austen, K. Frank

    1971-01-01

    The optimum conditions for antigen-induced release of histamine in the rat IgE and IgGa antibody-mediated systems were studied in vitro. The IgE antibody-mediated reaction could be separated into two steps: preparation of target cells with antibody and challenge with antigen. The optimal conditions for these two steps were distinctly different. Release of histamine by IgGa antibody and antigen could not be separated into two steps, and the optimal conditions for the total reaction were identical to those of the antigen challenge step of the IgE antibody-mediated system. PMID:4100657

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

    PubMed

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

    2015-01-01

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

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

    SciTech Connect

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

    1981-09-01

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

  3. Macelignan inhibits histamine release and inflammatory mediator production in activated rat basophilic leukemia mast cells.

    PubMed

    Han, Young Sun; Kim, Myung-Suk; Hwang, Jae-Kwan

    2012-10-01

    Type I allergy is characterized by the release of granule-associated mediators, lipid-derived substances, cytokines, and chemokines by activated mast cells. To evaluate the anti-allergic effects of macelignan isolated from Myristica fragrans Houtt., we determined its ability to inhibit calcium (Ca(2+)) influx, degranulation, and inflammatory mediator production in RBL-2 H3 cells stimulated with A23187 and phorbol 12-myristate 13-acetate. Macelignan inhibited Ca(2+) influx and the secretion of β-hexosaminidase, histamine, prostaglandin E(2), and leukotriene C(4); decreased mRNA levels of cyclooxygenase-2, 5-lipoxygenase, interleukin-4 (IL-4), IL-13, and tumor necrosis factor-α; and attenuated phosphorylation of Akt and the mitogen-activated protein kinases extracellular signal-regulated kinase, p38, and c-Jun N-terminal kinase. These results indicate the potential of macelignan as a type I allergy treatment.

  4. Optogenetic-Mediated Release of Histamine Reveals Distal and Autoregulatory Mechanisms for Controlling Arousal

    PubMed Central

    Williams, Rhîannan H.; Chee, Melissa J.S.; Kroeger, Daniel; Ferrari, Loris L.; Maratos-Flier, Eleftheria; Scammell, Thomas E.

    2014-01-01

    Histaminergic neurons in the tuberomammillary nucleus (TMN) are an important component of the ascending arousal system and may form part of a “flip–flop switch” hypothesized to regulate sleep and wakefulness. Anatomical studies have shown that the wake-active TMN and sleep-active ventrolateral preoptic nucleus (VLPO) are reciprocally connected, suggesting that each region can inhibit its counterpart when active. In this study, we determined how histamine affects the two branches of this circuit. We selectively expressed channelrhodopsin-2 (ChR2) in TMN neurons and used patch-clamp recordings in mouse brain slices to examine the effects of photo-evoked histamine release in the ventrolateral TMN and VLPO. Photostimulation decreased inhibitory GABAergic inputs to the ventrolateral TMN neurons but produced a membrane hyperpolarization and increased inhibitory synaptic input to the VLPO neurons. We found that in VLPO the response to histamine was indirect, most likely via a GABAergic interneuron. Our experiments demonstrate that release of histamine from TMN neurons can disinhibit the TMN and suppresses the activity of sleep-active VLPO neurons to promote TMN neuronal firing. This further supports the sleep–wake “flip–flop switch” hypothesis and a role for histamine in stabilizing the switch to favor wake states. PMID:24760861

  5. Qualitative characteristics of histamine release from human basophils by covalently cross-linked LgE

    SciTech Connect

    Kagey-Sobotka, A.; Dembo, M.; Goldstein, B.; Metzger, H.; Lichtenstein, L.M.

    1981-12-01

    The effects of permanent oligomers of human lgE produced was studied using the cross-linking reagent, dimethyl suberimidate, on histamine release from human basophils. lgE dimers were found to be sufficient stimuli for both release and desensitization of these cells; monomeric lgE had no effect. Histamine release was augmented by deuterium oxide (D/sub 2/O) in the media, but D/sub 2/O was not an absolute requirement to observe release. Desensitization by the dimeric lgE was specific in that the response to anti-lgE was not affected by preincubation of the leukocytes with the lgE dimer under suboptimal releasing conditions. lgE trimers and higher oligomers of lgE also caused both release and desensitization. lgE also trimers were 3- to 4-fold more effective than lgE dimers with regard to the amount required for 50% histamine release. Dilution studies with monomeric lgE suggested that the difference was due to the presence of more ''active'' dimers in the trimeric lgE fractions. We conclude that dimeric lgE, by juxtaposing 2 receptors on the basophil membrane, is the ''unit signal'' for both release and desensitization of these cells.

  6. PURIFICATION OF HISTAMINE SENSITIZING FACTOR OF BORDETELLA PERTUSSIS.

    DTIC Science & Technology

    Histamine Sensitizing Factor ( HSF ) of Bordetella pertussis was studied. To improve the cultivation method for HSF preparation, growth conditions of...maintenance and surface bulk culture was devised. Intracellular localization of HSF and lethal toxin were studied. HSF was mainly localized in the cell...wall prepared by Mickle disintegration, and toxin was found in protoplasm Ribosomes prepared from sonicate contained considerable amount of HSF and

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

    PubMed

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

    2016-01-27

    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.

  8. IMMUNOLOGICAL RELEASE OF HISTAMINE AND SLOW REACTING SUBSTANCE OF ANAPHYLAXIS FROM HUMAN LUNG

    PubMed Central

    Kaliner, Michael; Orange, Robert P.; Austen, K. Frank

    1972-01-01

    The immunologic release of histamine and slow reacting substance of anaphylaxis (SRS-A) from human lung tissue can be enhanced by stimulation with either alpha adrenergic agents (phenylephrine or norepinephrine in the presence of propranolol) or cholinergic agents (acetylcholine or Carbachol). The finding that atropine prevents cholinergic but not comparable alpha adrenergic enhancement is consistent with the view that cholinergic and alpha adrenergic agonists interact with separate receptor sites on the target cells involved in the immunologic release of chemical mediators. The consistent qualitative relationship between the antigen-induced release of mediators and the level of cyclic adenosine monophosphate (cyclic AMP) as measured by the isolation of 14C-labeled cyclic AMP after incorporation of adenine-14C into the tissues or by the cyclic AMP binding protein assay suggests that changes in the level of this cyclic nucleotide mediate adrenergic modulation of the release of histamine and SRS-A. The addition of 8-bromo-cyclic guanosine monophosphate (cyclic GMP) produces an enhancement of the immunologic release of mediators while dibutyryl cyclic AMP is inhibitory. As cholinergic-induced enhancement was not associated with a measurable change in the levels of cyclic AMP, the possibility is suggested that cyclic GMP may be the intracellular mediator of cholinergic-induced enhancement of the immunologic release of histamine and SRS-A. PMID:4115132

  9. Effect on gastric secretion, gastrin and histamine release during and after long-term treatment by pirenzepine in dogs.

    PubMed

    Vatier, J; Riquet, W; Célice-Pingaud, C; Olivier, A; Mignon, M; Farinotti, R

    1996-01-01

    We assessed the effects of pirenzepine (2 mg/kg per os) on gastric secretion and gastrin and histamine release in response to food and histamine dihydrochloride infusion in four dogs during 24 weeks of treatment and for 15 weeks after the end of treatment. The results were compared to those obtained in the same animals in control experiments, before treatment, and in four untreated dogs. Pirenzepine absorption was checked by measuring plasma concentrations. Pirenzepine led to a significant reduction in acid and pepsin secretion in response to histamine. In response to food, the reduction in secretion was concomitant with a reduction in gastrin and histamine release. Baseline concentrations of gastrin were reduced, while those of histamine were unchanged. No side effects were observed. After treatment, a long time lapse (about 15 weeks) was required for acid and pepsin secretion and gastrinemia to return to control levels, while histamine release in response to food normalized rapidly. Pirenzepine fixes selectively to M1 muscarinic receptors of the synaptic ganglion, thus inhibiting the effect of vagal stimulation, especially on pepsin secretion. Our data suggest that it might also fix to M1 receptors located on ECL cells, thereby reducing histamine release. In addition, pirenzepine probably fixes to other muscarinic receptors inhibiting gastrin release and resulting in a G and secretory cell mass reduction, probably by increasing somatostatin release.

  10. Histamine Release Associated with Intravenous Delivery of a Fluorocarbon-Based Sevoflurane Emulsion in Canines

    PubMed Central

    JOHNSON, REBECCA A.; SIMMONS, KEN T.; FAST, JONATHAN P.; SCHROEDER, CARRIE A.; PEARCE, ROBERT A.; ALBRECHT, RALPH M.; MECOZZI, SANDRO

    2011-01-01

    The purpose of this study was to evaluate the effectiveness of a novel fluorocarbon-based sevoflurane emulsion in dogs previously shown to produce short-term rodent anesthesia. On the basis of an unexpected allergic-type clinical reaction, we also tested the hypothesis that this type of formulation causes histamine release and complement activation. Physiological parameters, plasma histamine levels (radioimmunoassay), and complement activation (enzyme immunoassay) were quantified in response to emulsion components, including F13M5 (the emulsion’s fluorocarbon-based polymer) and methoxy poly(ethylene glycol) 5000 (the polymer’s hydrophilic block). Although the emulsion produced general anesthesia in dogs, they also experienced hypotension and clinical signs suggestive of an allergic-like response (i.e., vasodilation, urticaria, and pruritus upon recovery). Emulsions lacking sevoflurane failed to induce anesthesia but did elicit the allergic response. Plasma histamine levels were significantly increased following injection of micellar solutions of F13M5. Direct complement activation by the emulsion or its components was weak or absent. An allergic response leading to histamine release, likely initiated by the F13M5 component via an immunoglobulin pathway, is associated with an intravenous fluorocarbon-based emulsion of sevoflurane. Subsequently, its usefulness in medicine in its present formulation is limited. PMID:21246564

  11. [Surfactant-induced itching and the involvement of histamine released from keratinocytes].

    PubMed

    Inami, Yoshihiro; Andoh, Tsugunobu; Sasaki, Atsushi; Kuraishi, Yasushi

    2012-01-01

    The primary function of surfactants is to remove dirt, exfoliated corneum cells, and microorganisms from the skin. However, the use of toiletries such as soaps and shampoos containing surfactants may cause adverse effects such as cutaneous irritation, dryness, and itching. Recently, skin pathologies, including dry skin, rough skin, and sensitive skin, have increased because of changes in living conditions and lifestyle. Although many people with skin pathologies complain of itching during and/or after skin washing using detergents, the mechanisms of detergent-induced itch are yet to be elucidated. Therefore, in this study, we investigated the mechanisms underlying surfactant-induced itching. We found that topical application of an anionic surfactant sodium laurate at an alkaline pH, but not N-lauroylsarcosine sodium salt at neutral pH, to mouse skin induced scratching, an itch-related response. Additionally, we found that the sodium laurate-induced scratching was inhibited by H(1) histamine receptor antagonist, but not mast cell deficiency. Sodium laurate application increased histamine content and the level of the active form (53 kDa) of L-histidine decarboxylase (HDC) in the mouse epidermis, but not the dermis. Furthermore, addition of sodium laurate to a human epidermal cell culture increased histamine release and HDC levels, without affecting cell viability. These results suggest that surfactants with alkaline properties are pruritogenic and that the pruritus is induced by the histamine released from epidermal keratinocytes. The increase in histamine release may be attributable to the activation of HDC in epidermal keratinocytes.

  12. Characterization of histamine-releasing activity: role of cytokines and IgE heterogeneity.

    PubMed

    Liao, T N; Hsieh, K H

    1992-07-01

    Histamine-releasing factors (HRFs) are a group of cytokines that cause histamine release (HR) from basophils and mast cells. The concept of the priming effect of cytokines and the heterogeneity of IgE involved in the HRF-induced HR have been emphasized in recent years. In this study, we performed a series of experiments to elucidate the above-mentioned hypotheses. The stock HRF were obtained by stimulating mononuclear cells (MNC) with phytohemagglutinin (PHA). Maximal activity was observed 36 hr after culture. By gel filtration, HRF was eluted with a peak activity ranging from 12 to 18 KD. A large portion (75%) of HRF activity could be neutralized by a combination of antibodies against interleukin 1 (IL-1), IL-3, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha). The stimulation of basophils with 100 ng/ml each of IL-3, IL-6, IL-7, GM-CSF, or TNF-alpha alone caused 10% HR; however, when the cells were pretreated with 10 ng/ml of either IL-3, IL-6, IL-7, IL-8, TNF-alpha, or GM-CSF and then stimulated with anti-IgE, a marked increase in HR was regularly observed. The combination of 100 ng/ml each of IL-1, IL-3, IL-8, GM-CSF, and TNF-alpha could induce only about 20% HR; furthermore, such combinations did not have an additive or synergistic priming effect on anti-IgE-induced HR compared to the effect of single cytokines. Stripping of surface-bound IgE with lactic acid markedly reduced the capacity of basophils to release histamine in response to MNC-HRF and anti-IgE. Passive sensitization of IgE-stripped basophils with high-HRF responders' serum could restore their responsiveness to both MNC-HRF and anti-IgE, but passive sensitization with low-HRF responders' serum could restore responsiveness to anti-IgE only. Moreover, passage of MNC-HRF through high-, but not low-HRF, responders' IgE-Sepharose columns significantly reduced the HR activity of MNC-HRF. Finally, although the eluant could induce only 10% HR

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

    SciTech Connect

    Wescott, S.; Kaliner, M.

    1981-11-01

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

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

    PubMed

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

    1992-07-01

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

  15. Activation of basophil and mast cell histamine release by eosinophil granule major basic protein

    PubMed Central

    1983-01-01

    Major basic protein (MBP) is a primary constituent of eosinophil granules. In this report, we demonstrate that MBP from human eosinophil granules initiates a nonlytic histamine release from human leukocytes. A direct effect of MBP on basophils was confirmed using purified human basophils. The kinetics of release were similar to those reported for poly-L-arginine, although MBP was less potent than poly-L-arginine of similar molecular weight. Reduction and alkylation of MBP diminished both the potency and efficacy of the molecule. Native MBP also stimulated histamine secretion from purified rat peritoneal mast cells in a manner characteristic of other polycations. These results emphasize the bidirectional nature of the basophil/mast cell-eosinophil regulatory axis. PMID:6854212

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

    SciTech Connect

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

    1981-10-01

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

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

    PubMed

    Celuch, S M

    1995-12-12

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

  18. Evidence for lipoxygenase activity in induction of histamine release from rat peritoneal mast cells by chelated iron.

    PubMed

    Magro, A M; Brai, M

    1983-05-01

    The ferric iron-desferrioxamine B chelate effectively induced histamine release from rat peritoneal mast cells. The release was maximum at exogenous ferric iron concentrations of 10-100 microM, and the chelate was non-toxic, as determined by trypan blue uptake. In many aspects the chelate-induced histamine release paralleled IgE-mediated release. The kinetics, temperature, and Ca2+ dependence resembled antigen-induced release. Phosphatidylserine potentiated the release in Wistar rats but not in fawn-hooded rats, a strain which does not respond to phosphatidylserine potentiation. The chelate-induced histamine release was blocked by the metabolic inhibitors dinitrophenol, potassium cyanide, 2-deoxyglucose, and antimycin A. Lipoxygenase inhibitors also effectively blocked release, indicating an involvement of fatty acid metabolism via the lipoxygenase pathway. Free radical scavengers and antioxidants antagonistic to lipid peroxidation also inhibited the chelate-induced histamine release. Overall the data raise the possibility that endogenous cellular iron may be involved in the generation of free radicals and lipid peroxidation and that these may be early events in IgE-mediated release of histamine.

  19. Evidence for lipoxygenase activity in induction of histamine release from rat peritoneal mast cells by chelated iron.

    PubMed Central

    Magro, A M; Brai, M

    1983-01-01

    The ferric iron-desferrioxamine B chelate effectively induced histamine release from rat peritoneal mast cells. The release was maximum at exogenous ferric iron concentrations of 10-100 microM, and the chelate was non-toxic, as determined by trypan blue uptake. In many aspects the chelate-induced histamine release paralleled IgE-mediated release. The kinetics, temperature, and Ca2+ dependence resembled antigen-induced release. Phosphatidylserine potentiated the release in Wistar rats but not in fawn-hooded rats, a strain which does not respond to phosphatidylserine potentiation. The chelate-induced histamine release was blocked by the metabolic inhibitors dinitrophenol, potassium cyanide, 2-deoxyglucose, and antimycin A. Lipoxygenase inhibitors also effectively blocked release, indicating an involvement of fatty acid metabolism via the lipoxygenase pathway. Free radical scavengers and antioxidants antagonistic to lipid peroxidation also inhibited the chelate-induced histamine release. Overall the data raise the possibility that endogenous cellular iron may be involved in the generation of free radicals and lipid peroxidation and that these may be early events in IgE-mediated release of histamine. PMID:6188682

  20. Some characteristics of histamine secretion from rat peritoneal mast cells stimulated with nerve growth factor.

    PubMed Central

    Pearce, F L; Thompson, H L

    1986-01-01

    Nerve growth factor (NGF) isolated from mouse submandibular gland or from snake venom produced a dose-dependent release of histamine from isolated rat peritoneal mast cells. The response was almost totally dependent on the presence of extracellular calcium ions and on added phosphatidylserine or its lyso-derivative. At high concentrations, strontium ions could substitute for calcium. The process was non-cytotoxic, relatively slow, pH dependent and blocked by polyclonal antibodies to NGF. Binding of NGF to the mast cell was not dependent on added calcium. The release was unaffected by low molecular weight glucose polymers or specific quaternary ammonium salts and thus differed from that evoked by clinical dextran or polyamines. The release was not inhibited by soluble rat IgE or IgG and was unimpaired in mast cells recovered from specific pathogen free rats. As such it did not appear to be mediated through interaction with cell-fixed antibodies. The process further differed from anaphylactic histamine release in that there was no accompanying change in the intracellular level of adenosine 3',5'-cyclic monophosphate (cyclic AMP), the activated state induced by NGF was much more persistent than that evoked by antigen, and there was no cross-desensitization between the two latter stimuli. In total, these data suggest that NGF may induce secretion from rat mast cells by interaction with a specific receptor on the plasma membrane, possibly similar to that present on sensory and sympathetic neurones. PMID:2425086

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

    PubMed

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

    1992-04-01

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

  2. Immunological and non-immunological release of leukotrienes and histamine by guinea-pig heart.

    PubMed Central

    Salari, H

    1986-01-01

    Fragments of sensitized guinea-pig heart (1 g wet weight) were incubated with 5 micrograms/ml of antigen for up to 30 min, and the incubation media were analysed by reversed-phase high-performance liquid chromatography (RP-HPLC) for the presence of leukotrienes LTB4, LTC4, LTD4 and LTE4. Maximum release of LTB4, LTC4 and LTD4 was observed after 15 min (32.8 +/- 4, 8 +/- 2 and 9.5 +/- 2.5 pmol/g tissue wet weight, respectively, mean +/- SEM). At the same time, histamine was also released, reaching a maximum at 5 min (290 +/- 63 pmol/g tissue) as determined by radioenzymatic assay. Similarly, the non-sensitized guinea-pig heart stimulated with the ionophore A23187 (4 microM) released LTB4, LTC4, LTD4 and LTE4, as well as the 5-hydroxy-eicosatetraenoic acid (5-HETE), 12-HETE, and 15-HETE as determined by RP-HPLC. The release of LTB4, LTC4 and LTD4 was at a maximum after 10-15 min of stimulation (63 +/- 8.4, 10.7 +/- 2 and 17.5 +/- 4 pmol/g tissue). The ionophore also stimulated the release of histamine in heart tissue, with a peak maximum after 5 min (325 +/- 77 pmol/g tissue). These data demonstrate that heart as well as pulmonary tissues release significant amounts of leukotrienes and histamine during immunological or non-immunological challenges. PMID:2426186

  3. Histamine-releasing effect of a corticotrophin derivative. II. Mechanism of action of histamine release by C 44 680-Ba, compared with that of Cpd. 48/80, dextran and triton.

    PubMed

    Rüegg, M

    1979-06-01

    The mechanism of the histamine-liberating action of the synthetic polypeptide C 44 680-Ba, an alkyl-prolyl derivative of beta 1-19 corticotrophin, was investigated and compared with those of Compound 48/80, dextran, Melittin and Triton X-100. It was found that the release of histamine from rat peritoneal cells induced by the polypeptide is dependent on temperature, pH, calcium ions and energy-providing processes. In regard to these criteria, the mode of action of this histamine liberator resembles that of Compound 48/80 but is quite distinct from that of the unspecific substance Triton X-100.

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

    PubMed Central

    Fukugasako, Sanae; Ito, Shinichi; Ikemoto, Yoshimi

    2003-01-01

    Mechanisms of methyl p-hydroxybenzoate (methyl paraben) action in allergic reactions were investigated by measuring the intracellular Ca2+ concentration ([Ca2+]i) and histamine release in rat peritoneal mast cells (RPMCs). In the presence or absence of extracellular Ca2+, methyl paraben (0.1–10 mM) increased [Ca2+]i, in a concentration-dependent manner. Under both the conditions, methyl paraben alone did not evoke histamine release. In RPMCs pretreated with a protein kinase C (PKC) activator (phorbol 12-myristate 13-acetate (PMA) 3 and 10 nM), methyl paraben (0.3–3 mM) induced histamine release. However, a high concentration (10 mM) of the agent did not increase the histamine release. U73122 (0.1 and 0.5 μM), an inhibitor of phospholipase C (PLC), significantly inhibited the methyl paraben-induced histamine release in PMA-pretreated RPMCs. U73343 (0.5 μM), an inactive analogue of U73122, did not inhibit the histamine release caused by methyl paraben. In Ca2+-free solution, PLC inhibitors (U73122 0.1 and 0.5 μM, D609 1–10 μM) inhibited the methyl paraben-induced increase in [Ca2+]i, whereas U73343 (0.5 μM) did not. Xestospongin C (2–20 μM) and 2 aminoethoxydiphenyl borate (30 and 100 μM), blockers of the inositol 1,4,5-trisphosphate (IP3) receptor, inhibited the methyl paraben-induced increase in [Ca2+]i in Ca2+-free solution. In conclusion, methyl paraben causes an increase in [Ca2+]i, which may be due to release of Ca2+ from storage sites by IP3 via activation of PLC in RPMCs. In addition, methyl paraben possibly has some inhibitory effects on histamine release via unknown mechanisms. PMID:12770943

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

    PubMed Central

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

    2013-01-01

    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. PMID:23899970

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

    PubMed

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

    2013-07-29

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

  7. Characteristics of histamine release from rat mast cells in relation to the valency of the stimulating ligand.

    PubMed Central

    Healicon, R M; Foreman, J C

    1986-01-01

    The relationship between the valency of a ligand and the subsequent characteristics of histamine release was investigated in rat peritoneal mast cells. The cells were passively sensitized to the DNP hapten and a series of DNP-human serum albumin conjugates of known valency were used to induce histamine release. The rate of release of histamine induced by these conjugates was independent of the DNP/HSA ratio when the ratio was between 71.3 and 7.2. Marked slowing of the release occurred as the ratio was reduced below 7.2. The rate of desensitization of the cells slowed as a continuous function as the DNP/HSA ratio was reduced. 45Calcium uptake measurements showed that the changes in histamine release were paralleled by changes in the membrane permeability to calcium. The rate of release of histamine from mast cells and the rate of desensitization of the cells are discussed in terms of the size of IgE receptor complexes on the cell membrane. PMID:2420710

  8. Histamine Induces ATP Release from Human Subcutaneous Fibroblasts, via Pannexin-1 Hemichannels, Leading to Ca2+ Mobilization and Cell Proliferation*

    PubMed Central

    Pinheiro, Ana Rita; Paramos-de-Carvalho, Diogo; Certal, Mariana; Costa, Maria Adelina; Costa, Cristina; Magalhães-Cardoso, Maria Teresa; Ferreirinha, Fátima; Sévigny, Jean; Correia-de-Sá, Paulo

    2013-01-01

    Changes in the regulation of connective tissue ATP-mediated mechano-transduction and remodeling may be an important link to the pathogenesis of chronic pain. It has been demonstrated that mast cell-derived histamine plays an important role in painful fibrotic diseases. Here we analyzed the involvement of ATP in the response of human subcutaneous fibroblasts to histamine. Acute histamine application caused a rise in intracellular Ca2+ ([Ca2+]i) and ATP release from human subcutaneous fibroblasts via H1 receptor activation. Histamine-induced [Ca2+]i rise was partially attenuated by apyrase, an enzyme that inactivates extracellular ATP, and by blocking P2 purinoceptors with pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid) tetrasodium salt and reactive blue 2. [Ca2+]i accumulation caused by histamine was also reduced upon blocking pannexin-1 hemichannels with 10Panx, probenecid, or carbenoxolone but not when connexin hemichannels were inhibited with mefloquine or 2-octanol. Brefeldin A, an inhibitor of vesicular exocytosis, also did not block histamine-induced [Ca2+]i mobilization. Prolonged exposure of human subcutaneous fibroblast cultures to histamine favored cell growth and type I collagen synthesis via the activation of H1 receptor. This effect was mimicked by ATP and its metabolite, ADP, whereas the selective P2Y1 receptor antagonist, MRS2179, partially attenuated histamine-induced cell growth and type I collagen production. Expression of pannexin-1 and ADP-sensitive P2Y1 receptor on human subcutaneous fibroblasts was confirmed by immunofluorescence confocal microscopy and Western blot analysis. In conclusion, histamine induces ATP release from human subcutaneous fibroblasts, via pannexin-1 hemichannels, leading to [Ca2+]i mobilization and cell growth through the cooperation of H1 and P2 (probably P2Y1) receptors. PMID:23918924

  9. Modulation of gastric hemorrhage and ulceration by oxidative stress and histamine release in Salmonella typhimurium-infected rats.

    PubMed

    Hung, Chen-Road

    2005-01-01

    Infection with Salmonella typhimurium can produce multiple organ dysfunctions. However, document concerning with gastric hemorrhagic ulcers occur in this infectious disease is lacking. The aim was to study modulation of gastric hemorrhagic ulcer by oxidative stress and mast cell histamine in S. typhimurium-infected rats. Additionally, the protective effects of drugs, such as ofloxacin, lysozyme chloride, ketotifen, ranitidine, and several antioxidants, including exogenous glutathione (GSH), allopurinol and dimethylsulfoxide (DMSO) were evaluated. Male Wistar rats were injected intrajejunally with a live culture of S. typhimurium (1 x 10(10) colony-forming units/rat) and followed by deprivation of food for 36 h. Age-matched control rats received sterilized vehicle only. Rat stomachs were irrigated for 3 h with either normal saline or a simulated gastric juice containing 100 mM HCl, 17.4 mM pepsin and 54 mM NaCl. S. typhimurium caused aggravation of offensive factors, including enhancing gastric acid back-diffusion, mucosal lipid peroxide generation, histamine release, microvascular permeability and hemorrhagic ulcer, as well as an attenuation of defensive substances, such as mucosal GSH and mucus level. Intragastric irrigation of gastric juice caused further aggravation of these gastric biochemical parameters. This exacerbation of ulcerogenic factors was abolished by pretreatment of ofloxacin and lysozyme chloride. Antioxidants, such as reduced GSH, allopurinol and DMSO also produced significant (P < 0.05) amelioration of gastric damage in S. typhimurium infected rats. In conclusion, gastric oxidative stress and histamine play pivotal roles in the formation of hemorrhagic ulcers that were effectively ameliorated by ofloxacin, lysozyme chloride, ketotifen, ranitidine, diamine oxidase and various antioxidants in S. typhimurium-infected rats.

  10. Differential effect of cannabinoid agonists and endocannabinoids on histamine release from distinct regions of the rat brain

    PubMed Central

    Cenni, Gabriele; Blandina, Patrizio; Mackie, Ken; Nosi, Daniele; Formigli, Lucia; Giannoni, Patrizia; Ballini, Chiara; Corte, Laura Della; Mannaioni, Pier Francesco; Passani, M. Beatrice

    2006-01-01

    Cannabinoids exert complex actions on neurotransmitter systems involved in cognition, locomotion, appetite, but no information was available so far on the interactions between the endocannabinoid system and histaminergic neurons that command several, similar behavioural states and memory. In this study, we investigated the effect of cannabimimetic compounds on histamine release using the microdialysis technique in the brain of freely moving rats. We found that systemic administration of the cannabinoid receptors 1 (CB1-r) agonist arachidonyl-2′chloroethylamide/N-(2chloroethyl)-5Z,8Z,11Z,14Z-eicosatetraenamide (ACEA; 3 mg/kg) increased histamine release from the posterior hypothalamus, where the histaminergic tuberomamillary nuclei (TMN) are located. Local infusions of ACEA (150 nM) or R(+)-methanandamide (mAEA; 1μM), another CB1-r agonist, in the TMN augmented histamine release from the TMN, as well as from two histaminergic projection areas, the nucleus basalis magnocellularis and the dorsal striatum. When the endocannabinoid uptake inhibitor AM404 was infused into the TMN, however, increased histamine release was observed only in the TMN. The cannabinoid-induced effects on histamine release were blocked by co-administrations with the CB1-r antagonist AM251. Using double-immunofluorescence labelling and confocal laser-scanning microscopy, CB1-r immunostaining was found in the hypothalamus, but was not localized onto histaminergic cells. The modulatory effect of cannabimimetic compounds on histamine release apparently did not involve inhibition of γ-aminobutyric acid (GABA)ergic neurotransmission, which provides the main inhibitory input to the histaminergic neurons in the hypothalamus, as local infusions of ACEA did not modify GABA release from the TMN. These profound effects of cannabinoids on histaminergic neurotransmission may partially underlie some of the behavioural changes observed following exposure to cannabinoid-based drugs. PMID:17004927

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

    SciTech Connect

    Yen, A.; Gigli, I.; Barrett, K.E. )

    1990-06-01

    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.

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

    PubMed

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

    2001-04-01

    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.

  13. SG-HQ2 inhibits mast cell-mediated allergic inflammation through suppression of histamine release and pro-inflammatory cytokines.

    PubMed

    Je, In-Gyu; Kim, Hui-Hun; Park, Pil-Hoon; Kwon, Taeg Kyu; Seo, Seung-Yong; Shin, Tae-Yong; Kim, Sang-Hyun

    2015-05-01

    In this study, we investigated the effect of 3,4,5-trihydroxy-N-(8-hydroxyquinolin-2-yl)benzamide) (SG-HQ2), a synthetic analogue of gallic acid (3,4,5-trihydroxybenzoic acid), on the mast cell-mediated allergic inflammation and the possible mechanism of action. Mast cells play major roles in immunoglobulin E-mediated allergic responses by the release of histamine, lipid-derived mediators, and pro-inflammatory cytokines. We previously reported the potential effects of gallic acid using allergic inflammation models. For incremental research, we synthesized the SG-HQ2 by the modification of functional groups from gallic acid. SG-HQ2 attenuated histamine release by the reduction of intracellular calcium in human mast cells and primary peritoneal mast cells. The inhibitory efficacy of SG-HQ2 was similar with gallic acid. Enhanced expression of pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β, interleukin-4, and interleukin-6 in activated mast cells was significantly diminished by SG-HQ2 100 times lower concentration of gallic acid. This inhibitory effect was mediated by the reduction of nuclear factor-κB. In animal models, SG-HQ2 inhibited compound 48/80-induced serum histamine release and immunoglobulin E-mediated local allergic reaction, passive cutaneous anaphylaxis. Our results indicate that SG-HQ2, an analogue of gallic acid, might be a possible therapeutic candidate for mast cell-mediated allergic inflammatory diseases through suppression of histamine release and pro-inflammatory cytokines.

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

    PubMed

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

    2017-04-01

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

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

    PubMed

    Coulson, James; Thompson, John Paul

    2010-02-01

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

  16. Modulation of histamine-induced Ca2+ release by protein kinase C. Effects on cytosolic and mitochondrial [Ca2+] peaks.

    PubMed

    Montero, Mayte; Lobatón, Carmen D; Gutierrez-Fernández, Silvia; Moreno, Alfredo; Alvarez, Javier

    2003-12-12

    In HeLa cells, histamine induces production of inositol 1,4,5-trisphosphate (InsP3) and release of Ca2+ from the endoplasmic reticulum (ER). Ca2+ release is typically biphasic, with a fast and brief initial phase, followed by a much slower and prolonged one. In the presence of inhibitors of protein kinase C (PKC), including staurosporine and the specific inhibitors GF109203X and Ro-31-8220, the fast phase continued until the ER became fully empty. On the contrary, treatment with phorbol 12,13-dibutyrate inhibited Ca2+ release. Staurosporine had no effect on InsP3-induced Ca2+ release in permeabilized cells and did not modify either histamine-induced InsP3 production. These data suggest that histamine induces Ca2+ release and with a short lag activates PKC to down-regulate it. Consistently, Ca2+ oscillations induced by histamine were increased in amplitude and decreased in frequency in the presence of PKC inhibitors. We show also that mitochondrial [Ca2+] was much more sensitive to changes in ER-Ca2+ release induced by PKC modulation than cytosolic [Ca2+]. PKC inhibitors increased the histamine-induced mitochondrial [Ca2+] peak by 4-fold but increased the cytosolic [Ca2+] peak only by 20%. On the contrary, PKC activation inhibited the mitochondrial [Ca2+] peak by 90% and the cytosolic one by only 50%. Similarly, the combination of PKC inhibitors with the mitochondrial Ca2+ uniporter activator SB202190 led to dramatic increases in mitochondrial [Ca2+] peaks, with little effect on cytosolic ones. This suggests that activation of ER-Ca2+ release by PKC inhibitors could be involved in apoptosis induced by staurosporine. In addition, these mechanisms allow flexible and independent regulation of cytosolic and mitochondrial [Ca2+] during cell stimulation.

  17. Topical ophthalmic β blockers may cause release of histamine through cytotoxic effects on inflammatory cells

    PubMed Central

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

    2000-01-01

    AIM—To evaluate the effects of β blockers used in ophthalmology on the release of histamine from mixed cell preparations containing human leucocytes and basophils.
METHODS—A mixed leucocyte and basophil preparation was obtained from venous blood of healthy non-atopic volunteers. Cell preparations were then incubated with betaxolol, metipranolol, timolol, or carteolol. After incubation for 1 hour the histamine content of the supernatant was analysed by automated fluorometric analysis. Cell viability was tested by measuring lactate dehydrogenase (LDH) concentrations.
RESULTS—Betaxolol and metipranolol in concentrations between 10-2 M and 10-3 M liberated histamine from human blood cells in a dose dependent manner. Carteolol and timolol had no effect on histamine at these concentrations. At the same concentrations LDH was also detected in the supernatants of cell suspensions incubated with metipranolol or betaxolol.
CONCLUSIONS—Betaxolol and metipranolol induce substantial histamine release from human leucocytes, probably as a result of their cytotoxic effect.

 PMID:10966954

  18. Simultaneous detection of histamine release and lactate production in rat mast cells induced by compound 48/80 using sup 1 H NMR

    SciTech Connect

    Yoshizaki, Kazuo; Arizono, Naoki )

    1991-04-01

    {sup 1}H NMR spectroscopy was used to evaluate histamine release and lactate production in intact mast cells isolated from rats. The resonance lines of the aromatic histamine protons in mast cells, detected by the selective spin-excitation technique, were broader and located in a lower magnetic field than those in free histamine solution. When exocytosis of mast-cell granules was induced by compound 48/80, free histamine appeared, with a corresponding decrease in the amount of histamine in the mast cells; the lactate signal was also detected in the spectrum. On the addition of compound 48/ 80, there was a further release of histamine from mast cells, accompanied by further production of lactate. This result indicates that the mechanisms which induce the exocytosis of granules, and/or the events following exocytosis, activate glycolysis.

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

    NASA Astrophysics Data System (ADS)

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

    2012-05-01

    The effects of thermal stimuli on rat basophilic leukemia mast cells were studied. The cells in calcium-contained or calcium-free buffers were thermally stimulated in the temperature range of 25-60 °C. The corresponding calcium ion concentration in cells [Ca2+]i as well as the released histamine from cells was measured with fluorescence staining methods. The ruthenium red (RR), a block of membrane calcium channels (transient receptor potential family V (TRPV)), was used in experiments. Under the stimulus of 25-50 °C, no significant difference on [Ca2+]i was found between these three groups of the cells in calcium-contained buffer without or with RR and cells in calcium-free saline, indicating that the increased calcium in cytosol did not result from the extracellular buffer but came from the intracellular calcium stores. The [Ca2+]i continuously increased under the temperature of 50-60 °C, but the RR and calcium-free saline can obviously diminish the [Ca2+]i increase at these high temperatures, reflecting that the opening of the TRPV2 channels leads to a calcium influx resulting in the [Ca2+]i increment. The histamine release also became significant in these cases. Since the released histamine is a well-known mediator for the microcirculation promotion, the histamine release from mast cells could be one of the mechanisms of thermal therapy.

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

    PubMed

    Valle-Dorado, María Guadalupe; Santana-Gómez, César Emmanuel; Orozco-Suárez, Sandra Adela; Rocha, Luisa

    2015-05-01

    Experiments were designed to evaluate changes in the histamine release, mast cell number and neuronal damage in hippocampus induced by status epilepticus. We also evaluated if sodium cromoglycate, a stabilizer of mast cells with a possible stabilizing effect on the membrane of neurons, was able to prevent the release of histamine, γ-aminobutyric acid (GABA) and glutamate during the status epilepticus. During microdialysis experiments, rats were treated with saline (SS-SE) or sodium cromoglycate (CG-SE) and 30 min later received the administration of pilocarpine to induce status epilepticus. Twenty-four hours after the status epilepticus, the brains were used to determine the neuronal damage and the number of mast cells in hippocampus. During the status epilepticus, SS-SE group showed an enhanced release of histamine (138.5%, p = 0.005), GABA (331 ± 91%, p ≤ 0.001) and glutamate (467%, p ≤ 0.001), even after diazepam administration. One day after the status epilepticus, SS-SE group demonstrated increased number of mast cells in Stratum pyramidale of CA1 (88%, p < 0.001) and neuronal damage in dentate gyrus, CA1 and CA3. In contrast to SS-SE group, rats from the CG-SE group showed increased latency to the establishment of the status epilepticus (p = 0.048), absence of wet-dog shakes, reduced histamine (but not GABA and glutamate) release, lower number of mast cells (p = 0.008) and reduced neuronal damage in hippocampus. Our data revealed that histamine, possibly from mast cells, is released in hippocampus during the status epilepticus. This effect may be involved in the subsequent neuronal damage and is diminished with sodium cromoglycate pretreatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2015-11-01

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

  2. Role of histamine release in nonspecific vasodilatation during anodal and cathodal iontophoresis.

    PubMed

    Horiuchi, Yoshihito; Droog, Erik J; Henricson, Joakim; Wikström, Thore; Lennquist, Sten; Sjöberg, Folke

    2004-03-01

    Nonspecific vasodilatation during iontophoresis is an important confounding factor in experimental pharmacology. In this investigation, we studied the involvement of sensory nerves and histamine-related reactions in causing nonspecific vasodilatation in a model of anodal and cathodal iontophoresis of sodium chloride. Firstly, we applied a mixture of local anesthetic (EMLA) cream to confirm its suppressive effect on nonspecific vasodilatation and to measure its efficacy in three different dosages (duration: 1, 2, and 3 h). We then investigated the role of histamine in nonspecific vasodilatation by giving an oral antihistamine drug (cetirizine) to subjects who had and had not been given EMLA. We found substantial suppression of the nonspecific vasodilatation in all EMLA-treated groups (all dosages) compared with untreated controls (with suppression rates of 60-65%). Dosage had no significant effect. A further suppression of nonspecific vasodilatation was seen after oral cetirizine during anodal and cathodal iontophoresis in both EMLA-treated and untreated groups. The antihistamine effect was most pronounced during anodal iontophoresis. These results suggest a histaminergic increase in perfusion that may be independent of neurogenic mechanisms and depend on polarity (anode or cathode). Local nerve blocks (EMLA) together with cetirizine may therefore be used to reduce nonspecific vasodilatation in both anodal and cathodal iontophoresis.

  3. Histamine and chondroitin sulfate E proteoglycan released by cultured human colonic mucosa: indication for possible presence of E mast cells

    SciTech Connect

    Eliakim, R.; Gilead, L.; Ligumsky, M; Okon, E.; Rachmilewitz, D.; Razin, E.

    1986-01-01

    An association between the release of histamine and chondroitin sulfate E proteoglycan (PG) was demonstrates in human colonic mucosa (HCM). Colonic biopsy samples incorporated (/sup 35/S)sulfate into PG, which was partially released into the culture medium during the incubation period. Ascending thin-layer chromatography of the released /sup 35/S-labeled PG after its digestion by chondroitin ABC lyase (chondroitinase, EC 4.2.2.4) followed by autoradiography yielded three products that migrated in the position of monosulfated disaccharides of N-acetylgalactosamine 4-sulfate and N-acetylgalactosoamine 6-sulfate and of an oversulfated disaccharide possessing N-acetylgalatosamine 4,6-disulfate. Cultured colonic mucosa released 23.6 +/- 3.7ng of histamine per mg of wet tissue without any special trigger. Comparison by linear regression analysis of the release of histamine and chondroitin (/sup 35/S)sulfate E PG revealed a correlation coefficient (r) of 0.7. Histological examination of the colonic biopsies revealed the presence of many mast cells in various degrees of degranulation in the mucosa and submucosa. The above correlation, the observation that most of the mast cells showed various degrees of degranulation, and the lack of heparin synthesis as opposed to the synthesis and immunological release of chondroitin sulfate E strongly suggest that the E mast cell exists in the human colon.

  4. Histamine receptors in isolated bovine oviductal arteries.

    PubMed

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

    1997-05-20

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

  5. Isolation of mast cells from rabbit lung and liver: comparison of histamine release induced by the hypnotics Althesin and propanidid.

    PubMed

    Ennis, M; Lorenz, W; Gerland, W; Heise, J

    1987-04-01

    The enzyme collagenase was used to disperse rabbit lung and liver into their component cells. The resulting cell suspensions contained ca. 6.9% (lung) or 6.5% (liver) mast cells and were used in studies of histamine release without further purification. Both cell suspensions exhibited a low spontaneous release of histamine (ca. 6.6% lung, ca. 7.2% liver). Both cell types responded to challenge with anti-rabbit serum with a maximum release of the amine of ca. 22% (lung) and ca. 45% (liver). Concanavalin A challenge generally resulted in bell-shaped dose response curves, however some lung preparations did not respond. The rabbit cells were refractory to stimulation by Compound 48/80 and dextran. However a dose-dependent release of histamine was elicited after challenge with the detergents cremophor El, TN (12-hydroxystearic acid polymerized with ethylene oxide, degree of polymerization 15) and the hypnotics Althesin and propanidid. The maximum release observed depended on which cell preparation had been used. These results further emphasize the functional heterogeneity of mast cells from both different species and from different organs within the same species.

  6. The characteristics of inhibition of histamine release from human lung fragments by sodium cromoglycate, salbutamol and chlorpromazine

    PubMed Central

    Church, Martin K.; Young, Kevin D.

    1983-01-01

    1 Three drugs have been tested for activity against antigen-induced histamine release from passively sensitized human lung fragments after increasing periods of pre-incubation before challenge. 2 After 30 s pre-incubation, sodium cromoglycate inhibited histamine release in the concentration range 0.2-200 μM, producing a maximum inhibition of 33.0%. As the pretreatment period was extended, tolerance developed in a dose-related manner, resulting in a 48.3% and 82.8% loss of activity of the 200 μM dose after 60 min and 19 h pre-incubation, respectively. Tolerance was independent of extracellular calcium and was poorly reversible. Lung tissue desensitized to cromoglycate was cross-tolerant to the related drug, bufrolin, but not to salbutamol or chlorpromazine. 3 In acute studies, salbutamol (0.03-3.0 μM) produced dose-related inhibition of histamine release, with a maximum inhibition of 72.2%. The effect was blocked stereoselectively by 1 μM propranolol, suggesting that it occurred through an interaction with lung β-adrenoceptors. Increasing the pre-incubation time with salbutamol from 30 s to 19 h did not produce tolerance. Inhibition produced by incubation with salbutamol for 19 h was totally prevented when propranolol was added at the beginning of the pre-incubation period, indicating that it resulted from stimulation of β-receptors and not from a non-specific or toxic effect. However, studies of reversibility of effect through washing or late addition of propranolol did indicate some change in the nature of salbutamol inhibition with time. 4 Chlorpromazine was a weak inhibitor of immunological histamine release. A 100 μM concentration was ineffective after 30 s pre-incubation but its activity increased with time. Pre-incubation of lung fragments with this concentration for 1 h or longer, or with a 1 mM dose for a shorter period, provoked histamine release in the absence of antigen. Effects of chlorpromazine were not reversed by washing. 5 The different

  7. Adrenergic stimulation-released histamine taken-up in adrenergic nerves induces endothelium-dependent vasodilation in rat mesenteric resistance arteries.

    PubMed

    Haruki, Yuto; Takatori, Shingo; Hattori, Sayo; Zamami, Yoshito; Koyama, Toshihiro; Tangsucharit, Panot; Kawasaki, Hiromu

    2012-01-01

    The present study investigated whether histamine was taken up by perivascular adrenergic nerves and released by periarterial nerve stimulation (PNS) to induce vascular responses. In rat mesenteric vascular beds treated with capsaicin to eliminate calcitonin gene-related peptide (CGRP)ergic vasodilation and with active tone, PNS (1 - 4 Hz) induced only adrenergic nerve-mediated vasoconstriction. Histamine treatment for 20 min induced PNS-induced vasoconstriction followed by vasodilation without affecting CGRP-induced vasodilation. Chlorpheniramine, guanethidine, combination of histamine and desipramine, and endothelium-removal abolished PNS-induced vasodilation in histamine-treated preparations. These results suggest that histamine taken up by and released from adrenergic nerves by PNS causes endothelium-dependent vasodilation in rat mesenteric arteries.

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

    NASA Astrophysics Data System (ADS)

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

    2013-06-01

    We apply electric fields at different frequencies of 0.1, 1, 10 and 100 kHz to the rat basophilic leukemia (RBL) mast cells in calcium-containing or calcium-free buffers. The stimuli cause changes of the intracellular calcium ion concentration [Ca2+]i as well as the histamine. The [Ca2+]i increases when the frequency of the external electric field increases from 100 Hz to 10 kHz, and then decreases when the frequency further increases from 10 kHz to 100 kHz, showing a peak at 100 kHz. A similar frequency dependence of the histamine release is also found. The [Ca2+]i and the histamine releases at 100 Hz are about the same as the values of the control group with no electrical stimulation. The ruthenium red (RR), an inhibitor to the TRPV (transient receptor potential (TRP) family V) channels across the cell membrane, is used in the experiment to check whether the electric field stimuli act on the TRPV channels. Under an electric field of 10 kHz, the [Ca2+]i in a calcium-concentration buffer is about 3.5 times as much as that of the control group with no electric stimulation, while the [Ca2+]i in a calcium-free buffer is only about 2.2 times. Similar behavior is also found for the histamine release. RR blockage effect on the [Ca2+]i decrease is statistically significant (~75%) when mast cells in the buffer with calcium are stimulated with a 10 kHz electric field in comparison with the result without the RR treatment. This proves that TRPVs are the channels that calcium ions inflow through from the extracellular environment under electrical stimuli. Under this condition, the histamine is also released following a similar way. We suggest that, as far as an electric stimulation is concerned, an application of ac electric field of 10 kHz is better than other frequencies to open TRPV channels in mast cells, and this would cause a significant calcium influx resulting in a significant histamine release, which could be one of the mechanisms for electric therapy.

  9. Effect of terfenadine on pulmonary function, histamine release, and bronchial challenges with nebulized water and cold-air hyperventilation.

    PubMed

    Townley, R G; Hopp, R J; Bewtra, A K; Nabe, M

    1989-11-01

    To assess the effectiveness of terfenadine on bronchoconstriction in asthmatics, 12 asthmatic patients between the ages of 19 and 43 were challenged with ultrasonically nebulized distilled water (UNDW) and treated with terfenadine, 120 or 240 mg, or placebo in a three-way crossover double-blind study. A similar study of 12 asthmatics (nine from the UNDW trial) was performed using cold-air hyperventilation challenge (CAHC). In vitro analyses were also made of samples from ten mild asthmatics to determine the effect of terfenadine on basophil histamine release. Terfenadine, 240 mg, showed significant (P = .012) benefit over placebo in improving pulmonary function after UNDW challenge. Modest but significant (P less than .05) bronchodilator benefits were also demonstrated by terfenadine, 240 and 120 mg, after CAHC. Finally, the in vitro study showed significant inhibition by terfenadine of anti-IgE-induced histamine release from human basophils.

  10. Effect of various GABA-receptor agonists and antagonists on anaphylactic histamine release in the guinea-pig ileum.

    PubMed

    Luzzi, S; Franchi-Micheli, S; Ciuffi, M; Rosi, E; Zilletti, L

    1987-04-01

    In this paper we confirm the previously reported inhibition by GABA of anaphylactic histamine release from isolated guinea-pig ileum longitudinal muscle. Moreover we report that: GABA-inhibition of anaphylactic histamine release is mimicked both by GABA-A and GABA-B agonists; both GABA-A and GABA-B antagonists are effective in reversing GABA's inhibitory effect; the effect is exerted specifically by GABA-ergic drugs: taurine and beta-alanine are ineffective; the GABA-ergic effect seems not to involve cholinergic and adrenergic transmission. It is concluded that it might be interesting to assess the clinical value of GABA-ergic drugs in allergic gut disorders.

  11. Simultaneous detection of gastric acid and histamine release to unravel the regulation of acid secretion from the guinea pig stomach.

    PubMed

    Bitziou, Eleni; Patel, Bhavik Anil

    2012-08-01

    Gastric acid secretion is regulated by three primary components that activate the parietal cell: histamine, gastrin, and acetylcholine (ACh). Although much is known about these regulatory components individually, little is known on the interplay of these multiple activators and the degree of regulation they pose on the gastric acid secretion mechanism. We utilized a novel dual-sensing approach, where an iridium oxide sensor was used to monitor pH and a boron-doped diamond electrode was used for the detection of histamine from in vitro guinea pig stomach mucosal sections. Under basal conditions, gastrin was shown to be the main regulatory component of the total acid secretion and directly activated the parietal cell rather than by mediating gastric acid secretion through the release of histamine from the enterochromaffin-like cell, although both pathways were active. Under stimulated conditions with ACh, the gastrin and histamine components of the total acid secretion were not altered compared with levels observed under basal conditions, suggestive that ACh had no direct effect on the enterochromaffin-like cell and G cell. These data identify a new unique approach to investigate the regulation pathways active during acid secretion and the degree that they are utilized to drive total gastric acid secretion. The findings of this study will enhance our understanding on how these signaling mechanisms vary under pathophysiology or therapeutic management.

  12. The inhibition of mast cell damage and histamine release in anaphylaxis by pyridine and diphosphopyridine nucleotidase inhibitors. Comparison with compound 48/80

    PubMed Central

    Mota, Ivan; Da Silva, W. Dias; Fernandes, J. Ferreira

    1960-01-01

    In rats and guinea-pigs both mast cell damage and histamine release in anaphylaxis were inhibited by pyridine, nicotinamide, diethylnicotinamide, nicotinic acid, isonicotinic acid and isonicotinic acid hydrazide, which are known to be inhibitors of diphosphopyridine nucleotidases. On the other hand these compounds potentiated histamine release and mast cell damage by compound 48/80 in guinea-pigs although inhibiting the same phenomena in rats. The relationship of these findings with the mechanism of histamine liberation in anaphylaxis is discussed. PMID:13773170

  13. Histamine release and surface CD200R1 staining as sensitive methods for assessing murine mast cell activation.

    PubMed

    Larson, David; Mitre, Edward

    2012-05-31

    Mast cells are important effector cells of allergy and are involved in the pathology of many other diseases. Measurement of β-hexosaminidase activity, the most commonly used method for evaluation of murine mast cell activity, requires a large number of cells and thus is of limited utility for studying mast cells in mouse models of disease. In this study we evaluated the sensitivity of histamine release as compared to β-hexosaminidase activity in the measurement of mast cell activation. Whereas a minimum of 6×10(4) mast cells per ml were required to detect slight increases in β-hexosaminidase activity after anti-IgE and ionomycin stimulation, substantial increases in histamine release could be detected under the same activating conditions with as few as 480 mast cells per ml. These findings demonstrate that measurement of histamine release is substantially more sensitive than assessment of β-hexosaminidase activity for detecting mast cell activation. Additionally, we describe a novel flow cytometric method for detecting murine mast cell activation. When using 7.5×10(5) peritoneal cells per condition and gating on IgE+c-kit+cells, mast cell expression of surface CD200R1 increased after both IgE and non IgE-mediated activation. This flow cytometric procedure was uncomplicated and rapid, with increases in surface CD200R1 expression appearing after as little as 30 min of stimulation time. Measuring histamine release and surface CD200R1 expression are sensitive approaches for detection of murine mast cell activation. Further, both approaches can be done on unpurified peritoneal cell populations. By requiring low numbers of cells, these approaches are ideal for investigating mast cell activation in murine models of disease.

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

    PubMed

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

    2012-10-01

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

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

    SciTech Connect

    Danno, K.; Fujii, K.; Tachibana, T.; Toda, K.; Horio, T.

    1988-06-01

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

  16. Baicalein, wogonin, and Scutellaria baicalensis ethanol extract alleviate ovalbumin-induced allergic airway inflammation and mast cell-mediated anaphylactic shock by regulation of Th1/Th2 imbalance and histamine release.

    PubMed

    Bui, Thi Tho; Piao, Chun Hua; Song, Chang Ho; Lee, Chang-Hyun; Shin, Hee Soon; Chai, Ok Hee

    2017-06-01

    Asthma is characterized by chronic inflammation, goblet cell hyperplasia, the aberrant production of the Th2 cytokines, and eosinophil infiltration into the lungs. In this study, we examined the effects of baicalein, wogonin, and Scutellaria baicalensis ethanol extract on ovalbumin (OVA)-induced asthma by evaluating Th1/Th2 cytokine levels, histopathologic analysis, and compound 48/80-induced systemic anaphylaxis and mast cell activation, focusing on the histamine release from rat peritoneal mast cells. Baicalein, wogonin, and S. baicalensis ethanol extract also decreased the number of inflammatory cells especially eosinophils and downregulated peribronchial and perivascular inflammation in the lungs of mice challenged by OVA. Baicalein, wogonin, and S. baicalensis ethanol extract significantly reduced the levels of tumor necrosis factor α, interleukin (IL)-1β, IL-4, IL-5 and the production of OVA-specific IgE and IgG1, and upregulated the level of interferon-γ and OVA-specific IgG2a. In addition, oral administration of baicalein, wogonin, and S. baicalensis ethanol extract inhibited compound 48/80-induced systemic anaphylaxis and plasma histamine release in mice. Moreover, baicalein, wogonin, and S. baicalensis ethanol extract suppressed compound 48/80-induced mast cell degranulation and histamine release from rat peritoneal mast cells. Conclusively, baicalein and wogonin as major flavonoids of S. baicalensis may have therapeutic potential for allergic asthma through modulation of Th1/Th2 cytokine imbalance and histamine release from mast cells.

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

    SciTech Connect

    Lee, Dong-Hee; Kim, Sang-Hyun . E-mail: shkim72@knu.ac.kr; Eun, Jae-Soon; Shin, Tae-Yong . E-mail: tyshin@woosuk.ac.kr

    2006-11-01

    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-{alpha}, IL-8 and IL-6 secretion in human mast cells. The inhibitory effect of AEMD on the pro-inflammatory cytokines was nuclear factor-{kappa}B (NF-{kappa}B) dependent. AEMD decreased PMA and A23187-induced degradation of I{kappa}B{alpha} and nuclear translocation of NF-{kappa}B. Our findings provide evidence that AEMD inhibits mast cell-derived immediate-type allergic reactions and involvement of pro-inflammatory cytokines and NF-{kappa}B in these effects.

  18. Histamine as an Endothelium-Derived Relaxing Factor in Aged Mesenteric Lymphatic Vessels.

    PubMed

    Nizamutdinova, Irina Tsoy; Maejima, Daisuke; Nagai, Takashi; Meininger, Cynthia J; Gashev, Anatoliy A

    2017-06-01

    Knowledge of the mechanisms by which aging affects contracting lymphatic vessels remains incomplete; therefore, the functional role of histamine in the reaction of aged lymphatic vessels to increases in flow remains unknown. We measured and analyzed parameters of lymphatic contractility in isolated and pressurized rat mesenteric lymphatic vessels (MLVs) obtained from 9- and 24-month Fischer-344 rats under control conditions and after pharmacological blockade of nitric oxide (NO) by Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME, 100 μM) or/and blockade of histamine production by α-methyl-DL-histidine dihydrochloride (α-MHD, 10 μM). We also quantitatively compared results of immunohistochemical labeling of the histamine-producing enzyme, histidine decarboxylase (HDC) in adult and aged MLVs. Our data provide the first demonstration of an increased functional role of histamine as an endothelial-derived relaxing factor in aged MLVs, which appears in parallel with the abolished role of NO in the reactions of these lymph vessels to increases in flow. In addition, we found an increased expression of HDC in endothelium of aged MLVs. Our findings provide the basis for better understanding of the processes of aging in lymphatic vessels and for setting new important directions for investigations of the aging-associated disturbances in lymph flow and the immune response.

  19. Effects of C18 Fatty Acids on Intracellular Ca(2+) Mobilization and Histamine Release in RBL-2H3 Cells.

    PubMed

    Kim, Myung Chul; Kim, Min Gyu; Jo, Young Soo; Song, Ho Sun; Eom, Tae In; Sim, Sang Soo

    2014-06-01

    To investigate the underlying mechanisms of C18 fatty acids (stearic acid, oleic acid, linoleic acid and α-linolenic acid) on mast cells, we measured the effect of C18 fatty acids on intracellular Ca(2+) mobilization and histamine release in RBL-2H3 mast cells. Stearic acid rapidly increased initial peak of intracellular Ca(2+) mobilization, whereas linoleic acid and α-linolenic acid gradually increased this mobilization. In the absence of extracellular Ca(2+), stearic acid (100 µM) did not cause any increase of intracellular Ca(2+) mobilization. Both linoleic acid and α-linolenic acid increased intracellular Ca(2+) mobilization, but the increase was smaller than that in the presence of extracellular Ca(2+). These results suggest that C18 fatty acid-induced intracellular Ca(2+) mobilization is mainly dependent on extracellular Ca(2+) influx. Verapamil dose-dependently inhibited stearic acid-induced intracellular Ca(2+) mobilization, but did not affect both linoleic acid and α-linolenic acid-induced intracellular Ca(2+) mobilization. These data suggest that the underlying mechanism of stearic acid, linoleic acid and α-linolenic acid on intracellular Ca(2+) mobilization may differ. Linoleic acid and α-linolenic acid significantly increased histamine release. Linoleic acid (C18:2: ω-6)-induced intracellular Ca(2+) mobilization and histamine release were more prominent than α-linolenic acid (C18:3: ω-3). These data support the view that the intake of more α-linolenic acid than linoleic acid is useful in preventing inflammation.

  20. Effects of C18 Fatty Acids on Intracellular Ca2+ Mobilization and Histamine Release in RBL-2H3 Cells

    PubMed Central

    Kim, Myung Chul; Kim, Min Gyu; Jo, Young Soo; Song, Ho Sun; Eom, Tae In

    2014-01-01

    To investigate the underlying mechanisms of C18 fatty acids (stearic acid, oleic acid, linoleic acid and α-linolenic acid) on mast cells, we measured the effect of C18 fatty acids on intracellular Ca2+ mobilization and histamine release in RBL-2H3 mast cells. Stearic acid rapidly increased initial peak of intracellular Ca2+ mobilization, whereas linoleic acid and α-linolenic acid gradually increased this mobilization. In the absence of extracellular Ca2+, stearic acid (100 µM) did not cause any increase of intracellular Ca2+ mobilization. Both linoleic acid and α-linolenic acid increased intracellular Ca2+ mobilization, but the increase was smaller than that in the presence of extracellular Ca2+. These results suggest that C18 fatty acid-induced intracellular Ca2+ mobilization is mainly dependent on extracellular Ca2+ influx. Verapamil dose-dependently inhibited stearic acid-induced intracellular Ca2+ mobilization, but did not affect both linoleic acid and α-linolenic acid-induced intracellular Ca2+ mobilization. These data suggest that the underlying mechanism of stearic acid, linoleic acid and α-linolenic acid on intracellular Ca2+ mobilization may differ. Linoleic acid and α-linolenic acid significantly increased histamine release. Linoleic acid (C18:2: ω-6)-induced intracellular Ca2+ mobilization and histamine release were more prominent than α-linolenic acid (C18:3: ω-3). These data support the view that the intake of more α-linolenic acid than linoleic acid is useful in preventing inflammation. PMID:24976764

  1. Comparative study of the membrane-permeabilizing activities of mastoparans and related histamine-releasing agents in bacteria, erythrocytes, and mast cells.

    PubMed

    Nakao, Satoshi; Komagoe, Keiko; Inoue, Tsuyoshi; Katsu, Takashi

    2011-01-01

    The membrane-permeabilizing activities of mastoparans and related histamine-releasing agents were compared through measurements of K(+) efflux from bacteria, erythrocytes, and mast cells. Changes in bacterial cell viability, hemolysis, and histamine release, as well as in the shape of erythrocytes were also investigated. The compounds tested were mastoparans (HR1, a mastoparan from Polistes jadwagae, and a mastoparan from Vespula lewisii), granuliberin R, mast cell-degranulating peptide, and compound 48/80, as well as antimicrobial peptides, such as magainin I, magainin II, gramicidin S, and melittin. We used a K(+)-selective electrode to determine changes in the permeability to K(+) of the cytoplasmic membranes of cells. Consistent with the surface of mast cells becoming negatively charged during histamine release, due to the translocation of phosphatidylserine to the outer leaflet of the cytoplasmic membrane, histamine-releasing agents induced K(+) efflux from mast cells, dependent on their ability to increase the permeability of bacterial cytoplasmic membranes rich in negatively charged phospholipids. The present results demonstrated that amphiphilic peptides, possessing both histamine-releasing and antimicrobial capabilities, induced the permeabilization of the cytoplasmic membranes of not only bacteria but mast cells. Mastoparans increased the permeability of membranes in human erythrocytes at higher concentrations, and changed the normal discoid shape to a crenated form. The structural requirement for making the crenated form was determined using compound 48/80 and its constituents (monomer, dimer, and trimer), changing systematically the number of cationic charges of the molecules.

  2. [Cerebral ischemia and histamine].

    PubMed

    Adachi, Naoto

    2002-10-01

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

  3. Nedocromil sodium inhibits antigen-induced contraction of human lung parenchymal and bronchial strips, and the release of sulphidopeptide-leukotriene and histamine from human lung fragments.

    PubMed Central

    Napier, F. E.; Shearer, M. A.; Temple, D. M.

    1990-01-01

    1. The effects of nedocromil sodium on antigen-induced release of sulphidopeptide-leukotrienes and histamine from passively sensitized fragments of human lung, and on antigen-induced contraction of sensitized strips of human lung parenchyma and bronchus, have been studied. 2. Nedocromil sodium 0.1 and 1 microM inhibited leukotriene release from fragments of human lung by 30% and 38% respectively, and histamine release by 43% for both concentrations, but 10 microM was ineffective. The lung fragments, which were passively sensitized to house dust mite, Dermataphagoides pteronyssinus, in control experiments released leukotrienes (6.58 +/- 0.12 nmol equiv. leukotriene C4 per g, n = 6) and histamine (10.3 +/- 1.8 of total tissue histamine, n = 5) when challenged with house dust mite extract. 3. Isolated strips of human lung parenchyma, passively sensitized to D. pteronyssinus, contracted when treated with house dust mite extract to a mean value of 40% of the maximal histamine response for each strip. Nedocromil sodium 0.1 and 1 microM inhibited these contractions by 50% and 70% of the control response, but 10 microM had no inhibitory effect. 4. Isolated rings from human bronchus, also passively sensitized to D. pteronyssinus, contracted when treated with house dust mite extract to a mean value of 86% of the maximal histamine response. Nedocromil sodium 1 microM, but not 0.1 or 10 microM, inhibited contractions by 48% of the control response. 5. The therapeutic effects of nedocromil sodium in allergic asthma may depend, partly, on its inhibition of antigen-induced release of leukotrienes and histamine in human lung and its consequent inhibition of antigen-induced contractions of parenchymal and bronchial tissue. PMID:1696152

  4. Plasma histamine concentration and histamine detection in peripheral blood eosinophils in cats.

    PubMed

    Kadoya, Michiyo; Momoi, Yasuyuki; Iwasaki, Toshiroh

    2006-10-01

    Plasma histamine levels were measured in 11 clinically healthy cats and 15 cats with allergic dermatitis. Histamine levels were markedly elevated in 5/15 allergic cats. A calcium ionophore, A23187, stimulates histamine release from feline peripheral blood cells. Immunostaining of blood smears from clinically healthy cats revealed that approximately 10% of eosinophils possessed histamine-containing granules. These results indicate that some peripheral eosinophils in cats contain histamine and can release histamine by appropriate stimulation.

  5. Preliminary characterization of diacylglycerol generation in human basophils: temporal relationship to histamine release and resolution of degranulation.

    PubMed

    Oriente, A; Hundley, T; Hubbard, W C; MacGlashan, D W

    1997-05-01

    Purified human basophils were examined for changes in diacylglycerol levels to determine whether the transient nature of a N-formyl-methionyl-leucyl-phenylalanine (fMLP) -stimulated elevation in membrane protein kinase C (PKC) activity could be explained by the transient production of diacylglycerol (DAG). In preliminary experiments total DAG levels were measured by the DAG kinase assay. Although elevations followed stimulation with 1 microM fMLP (basal levels of 15 pmol/10(6) basophils vs. 45 pmol/10(6) basophils at the 3-min time point), there were no detectable changes in the first 60 s of the reaction. Histamine release is typically complete by 30-45 s. Measurement of inositol trisphosphate indicated a rapid increase by 5 s of 2.5 pmol/10(6) basophils. If DAG were produced at similar levels, the DAG kinase assay would not have detected the elevation. Consequently, fMLP-stimulated basophils were examined for changes in 1-stearoyl, 2-arachidonoyl, 3-sn-glycerol (SA-DAG) and 1-oleoyl, 2-arachidonoyl, 3-sn-glycerol by GC-NICIMS (negative ion chemical ionization mass spectroscopy). A 5-s elevation in these two species averaged 2 pmol/10(6) basophils, consistent with the inositol trisphosphate levels and occurring during the period of histamine release. However, a much more pronounced second phase to the SA-DAG response also occurred, mirroring the total DAG levels. This second phase of the DAG response, either total or SA-DAG, was transient on a time scale temporally coincident with the appearance and resolution of degranulation sacs as measured by fluorescence microscopy. These data suggest that there is selective generation of DAG species in the early reaction and the later appearance of DAG may be related to the formation and resolution of granule structures that follow the secretion of histamine.

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

    PubMed

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

    2015-01-01

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

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

    DTIC Science & Technology

    1975-06-01

    radiation of two untreated monkeys, four monkeys given chlorpheniramine 30 minutes before irradiation and four monkeys treated with 48/80 for four...antagonist, chlorpheniramine ’ (3 mg/kg), 30 minutes before irradiation. Experiment 3. Seven monkeys were given aminoguanidine and 30 minutes later the...4000-rad dose of ionizing radiation in animals receiving no treatment. When the animals were pretreated with chlorpheniramine , the histamine

  8. Histamine H3-receptor stimulation is unable to modulate noradrenaline release by the isolated rat heart during ischaemia-reperfusion.

    PubMed

    Mazenot, C; Durand, A; Ribuot, C; Demenge, P; Godin-Ribuot, D

    1999-01-01

    The aim of this study was to evaluate the ability of H3-histaminergic prejunctional receptors to modulate the noradrenaline release induced by myocardial ischaemia in the rat, and the effects of an eventual modulation on haemodynamic, biochemical and electrophysiological parameters. Isolated rat hearts were perfused according to the Langendorff technique. Control hearts (n = 13) were not treated; two groups were treated with the H3-agonist R-alpha-methyl-histamine at 0.3 microM (n = 14) and 1 microM (n = 11) and one group, used as positive control, was treated with the selective alpha 2-agonist Mivazerol at 0.5 microM (n = 14) added to the perfusion medium. Noradrenaline, lactate and transaminase output in the coronary effluent, as well as various haemodynamic and electrophysiological parameters, were measured during global and total ischaemia (30 min) and reperfusion (30 min). alpha 2-receptor stimulation increased ischaemia-induced noradrenaline release during reperfusion (195 +/- 13 vs. 145 +/- 12 pmol.g-1 in control group, P < 0.05). In contrast, R-alpha-methyl-histamine, at both doses, did not significantly modify these parameters. Both treatments did not affect ischaemia- and reperfusion-induced haemodynamic (decrease in heart rate or in left ventricular developed pressure), biochemical (lactate and GOT release) and electrophysiological (arrhythmias or increase in action potential duration) alterations. Unlike other species, the rat appears to be insensitive to H3-histaminergic receptor modulation of ischaemia-induced noradrenaline release, although a modulation can be seen with other prejunctional receptor agonists.

  9. Comparison of the effect of an H(3)-inverse agonist on energy intake and hypothalamic histamine release in normal mice and leptin resistant mice with high fat diet-induced obesity.

    PubMed

    Ishizuka, Tomoko; Hatano, Kouta; Murotani, Tomotaka; Yamatodani, Atsushi

    2008-04-09

    Leptin is a key signal linking peripheral adiposity levels to the regulation of energy homeostasis in the brain. The injection of leptin decreases body weight and food intake in lean rodents; however, in a rodent model of high fat diet-induced obesity (DIO), the exogenous leptin cannot improve adiposity. This ineffectiveness is known as leptin resistance, and the factors downstream of leptin signaling have received attention as viable targets in the treatment of obesity. We previously reported that the histaminergic system is one of the targets of leptin. In the present study, the effect of an H(3)-receptor inverse agonist on hypothalamic histamine release and energy intake was investigated in normal and DIO mice. Leptin (1.3 mg/kg, i.p.) significantly increased hypothalamic histamine release and reduced 12 h-energy intake in normal mice, but had no such effects in DIO mice. In contrast, clobenpropit (5 mg/kg, i.p.), an H(3)-inverse agonist, elicited a significant increase in histamine release in both types of mice. Clobenpropit did not reduce 12 h-energy intake; however, it decreased 3 h-energy intake in both types of mice. These results suggest that lack of the activation of the histaminergic system partly contributes to obesity in DIO mice and direct activation of the histaminergic system circumvents leptin resistance.

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

    PubMed

    Schlicker, E; Schunack, W; Göthert, M

    1990-11-01

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

  11. Skin tests and histamine release with P1-depleted Dermatophagoides pteronyssinus body extracts and purified P1.

    PubMed

    van der Zee, J S; van Swieten, P; Jansen, H M; Aalberse, R C

    1988-05-01

    Monoclonal antibodies were raised against P1 and Dp X, two major allergens in Dermatophagoides pteronyssinus extracts. The concentrations of IgE antibodies to P1 and Dp X in sera of mite-sensitive patients were determined in RAST with immunosorbent-bound monoclonal antibodies used for insolubilization of the allergens. The major allergen-specific IgE titers were compared with the total IgE response against D. pteronyssinus. The results of these serologic assays confirmed studies in the literature that P1 and Dp X are major allergens. The contribution of IgE anti-P1 to the total antimite response frequently exceeded 50% and, in general, appeared to be higher than the contribution of IgE anti-Dp X. Twenty percent of the mite-sensitive patients had no detectable IgE to either P1 or Dp X. The contribution of P1 to the biologic activity of D. pteronyssinus body extracts was derived from the effect of P1 depletion on the reactivity in the histamine-release test and skin test. This technique was preferred to the study of purified allergen because biologic activity of the nonabsorbed components is not affected. Immunization of rabbits with affinity-purified P1 yielded monospecific polyclonal antisera. Mite extracts depleted with either monoclonal or polyclonal anti-P1 were applied in the histamine-release test. The skin test was performed with extracts depleted with polyclonal anti-P1. In addition, the activity of affinity-purified P1 was investigated in these tests. The results indicated that P1 depletion of D. pteronyssinus body extracts had no detectable effect on the activity in most patients, namely, at least 70% of the activity was retained in the depleted extract. There was a considerable variation between patients in the sensitivity for purified P1, as compared to the sensitivity for whole D. pteronyssinus extracts. In the histamine-release test, the activity of purified P1 was up to 35% of the activity of the D. pteronyssinus body extract but did not exceed 10% in

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

    PubMed Central

    1985-01-01

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

  13. Competitive inhibition of 48/80-induced histamine release by benzalkonium chloride and its analogs and the polyamine receptor in mast cells.

    PubMed

    Read, G W; Hong, S M; Kiefer, E F

    1982-09-01

    Benzalkonium Cl is a family of benzyldimethylalkylammonium compounds which are selective inhibitors of histamine release induced by 48/80 and many other polyamines, but do not inhibit histamine release caused by antigen-antibody reactions, ionophores, enzymes or detergents. In this study, additional histamine-releasing poly- and monoamines found to be antagonized by benzalkonium Cl in rat mast cells were cadaverine, hexamethonium, decamethonium, lysine, dilysine, trilysine, pentalysine, mellitin, pentamidine, spermidine, spermine, morphine, norepinephrine and tyramine. Benzyldimethyltetradecylammonium Cl, one of the safest and most potent members of the benzalkonium Cl family, was found to antagonize 48/80-induced histamine release by a competitive mechanism. Benzyldimethyltetradecylammonium Cl was also found to inhibit 48/80-induced histamine release from mast cells of the hamster in vitro and in the rat, cat and mongoose in vivo. Structure-activity relations studies revealed that: 1) substitution of alkyl, cycloalkyl or other aryl groups for the benzyl group of benzyldimethyltetradecylammonium Cl reduced activity only slightly; 2) demethylation to form the tertiary or secondary amines dramatically reduced activity; 3) optimal length of the alkyl side chain was usually 12 to 14 carbons; and 4) replacement of the nitrogen with phosphorus or sulfur did not significantly alter activity. It appears that the polyamine receptor on mast cells is: 1) widespread in mammals; 2) stimulated by a broad range of polyamines and some monoamines; 3) responsive both in vitro and in vivo; and 4) competitively antagonized by a fairly diverse family of inhibitors possessing a permanent positive charge attached to a substantial but limited hydrophobic moiety.

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

    PubMed

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

    2016-07-01

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

  15. [In vitro comparative study of the protective effect of different theophyllines on the leucocytes' histamine-release induced by antigen (author's transl)].

    PubMed

    Biot, N; Grosclaude, M; Kofman, J; Perrin-Fayolle, M

    1980-01-01

    The recent discovery of the protective action of xanthic bases towards histamine-release consecutive to the antigen-antibody reaction led the authors to study the importance of this protection induced by various theophylline derivatives. The technique used was that described by LICHTENSTEIN and OSLER: isolation of leucocytes, measurement of histamine liberated in the presence of antigen, same measurement done in the presence of antigen and theophylline. The antigens used were: house dust, Dermatophagoides pteronyssimus (DP), graminaceae pollens. The tested theophyllines were: the theophylline base, aminophylline, bamiphylline, diprophylline, thio theo, piperazine acefilinate. All these substances studied brought a reduction of the histamine-release but according to a variable frequency and intensity: the thio theo, the diprophylline and the piperazine acefilinate gave the best results. Besides the latters are clearer when the antigen was dust or DP. This study enables the confirmation of the inhibiting action of theophyllines on histamine-release induced by antigen, but complementary studies on a larger number of cases seem necessary in order to determine precisely the most efficient derivatives.

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

    PubMed

    Hasan, Samer; Al Ali, Hussein; Al-Qubaisi, Mothanna; Zobir Hussein, Mohd; Ismail, Maznah; Zainal, Zulkarnain; Nazrul Hakim, Muhammad

    2012-01-01

    A controlled-release formulation of an antihistamine, cetirizine, was synthesized using zinc-layered hydroxide as the host and cetirizine as the guest. The resulting well-ordered nanolayered structure, a cetirizine nanocomposite "CETN," had a basal spacing of 33.9 Å, averaged from six harmonics observed from X-ray diffraction. The guest, cetirizine, was arranged in a horizontal bilayer between the zinc-layered hydroxide (ZLH) inorganic interlayers. Fourier transform infrared spectroscopy studies indicated that the intercalation takes place without major change in the structure of the guest and that the thermal stability of the guest in the nanocomposites is markedly enhanced. The loading of the guest in the nanocomposites was estimated to be about 49.4% (w/w). The release study showed that about 96% of the guest could be released in 80 hours by phosphate buffer solution at pH 7.4 compared with about 97% in 73 hours at pH 4.8. It was found that release was governed by pseudo-second order kinetics. Release of histamine from rat basophilic leukemia cells was found to be more sensitive to the intercalated cetirizine in the CETN compared with its free counterpart, with inhibition of 56% and 29%, respectively, at 62.5 ng/mL. The cytotoxicity assay toward Chang liver cells line show the IC₅₀ for CETN and ZLH are 617 and 670 μg/mL, respectively.

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

    PubMed Central

    Hasan, Samer; Ali, Hussein Al; Al-Qubaisi, Mothanna; Hussein, Mohd Zobir; Ismail, Maznah; Zainal, Zulkarnain; Hakim, Muhammad Nazrul

    2012-01-01

    A controlled-release formulation of an antihistamine, cetirizine, was synthesized using zinc-layered hydroxide as the host and cetirizine as the guest. The resulting well-ordered nanolayered structure, a cetirizine nanocomposite “CETN,” had a basal spacing of 33.9 Å, averaged from six harmonics observed from X-ray diffraction. The guest, cetirizine, was arranged in a horizontal bilayer between the zinc-layered hydroxide (ZLH) inorganic interlayers. Fourier transform infrared spectroscopy studies indicated that the intercalation takes place without major change in the structure of the guest and that the thermal stability of the guest in the nanocomposites is markedly enhanced. The loading of the guest in the nanocomposites was estimated to be about 49.4% (w/w). The release study showed that about 96% of the guest could be released in 80 hours by phosphate buffer solution at pH 7.4 compared with about 97% in 73 hours at pH 4.8. It was found that release was governed by pseudo-second order kinetics. Release of histamine from rat basophilic leukemia cells was found to be more sensitive to the intercalated cetirizine in the CETN compared with its free counterpart, with inhibition of 56% and 29%, respectively, at 62.5 ng/mL. The cytotoxicity assay toward Chang liver cells line show the IC50 for CETN and ZLH are 617 and 670 μg/mL, respectively. PMID:22848164

  18. H1-histamine receptors may mediate the contractile response of guinea-pig ileum to 'histamine-free' splenic extracts.

    PubMed Central

    Ainz, L. F.; Casis, E.; de Gandarias, J. M.; Gil-Rodrigo, C. E.; Goiriena de Gandarias, J. J.

    1983-01-01

    A water-soluble splenic factor, which produces a contractile response of the guinea-pig ileum, that is resistant to cholinoceptor and adrenoceptor antagonists is described. The ileal contractions elicited by the splenic extract showed some significant differences from those elicited by 5-hydroxytryptamine. The responses to splenic extract were not affected by the D-tryptamine-receptor antagonist, methysergide. The effect of the splenic extract on the guinea-pig ileum was similar to that of histamine. The H1-histamine antagonists, (+)-chloropheniramine and diphenhydramine, caused a parallel shift to the right of the splenic extract dose-response curve without suppression of the maximum response. A pA2 value of 8.97 +/- 0.03 for (+)-chloropheniramine and 7.55 +/- 0.1 for diphenhydramine was calculated. Significant histamine levels, as determined by fluorometric methods, could not be detected in the splenic extract. Likewise, the splenic factor did not release histamine from the intestinal preparation. These results support the view that: (i) the splenic factor acts through H1-histamine receptors; (ii) it is not histamine; (iii) it does not have any histamine releasing effect on the ileal smooth muscle. PMID:6652334

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

    SciTech Connect

    Tung, R.; Lichtenstein, L.M.

    1982-05-01

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

  20. Plasma histamine and tumour necrosis factor-alpha levels in Crohn's disease and ulcerative colitis at various stages of disease.

    PubMed

    Hagel, A F; de Rossi, T; Konturek, P C; Albrecht, H; Walker, S; Hahn, E G; Raithel, M

    2015-08-01

    Mast cells secrete numerous mediators and this study investigated plasma levels of histamine, and tumor necrosis factor alpha (TNF-α) in chronic inflammatory bowel disease (IBD). Plasma levels of histamine were determined in 68 patients with Crohn's disease (CD), 22 with ulcerative colitis (UC) and 13 controls. TNF-α levels were assessed in 29 CD patients, 11 UC patients, and in 11 controls. Plasma histamine levels in the control group were 0.25 ng (0.14 - 0.33) and showed no difference to CD (0.19 ng, 0.09 - 0.35) or UC (0.23 ng, 0.11 - 0.60). Significantly lower histamine levels were only found in CD patients on 5-aminosalicylic acid treatment (P ≤ 0.04). Plasma TNF-α levels in the control group were significantly lower 0.44 ml/m(2) (0 - 1.15) than in CD patients (4.62 ml/m(2), 1.82 - 9.22, P = 0.005) or UC (3.14 ml/m(2); 0.08 - 11.34, P = 0.01). In CD disease activity, fistula, and extraintestinal manifestations (EM) were associated with significantly higher plasma TNF-α values, but not the type of treatment. We concluded that in contrast to TNF-α, histamine levels were normal in CD and UC. There is no correlation with histamine and thus the proportion of TNF-α secreted from mast cells in the plasma in patients with IBD is less important.

  1. Stimulation by thimerosal of histamine-induced Ca(2+) release in intact HeLa cells seen with aequorin targeted to the endoplasmic reticulum.

    PubMed

    Montero, M; Barrero, M J; Torrecilla, F; Lobatón, C D; Moreno, A; Alvarez, J

    2001-09-01

    The oxidizing thiol reagent, thimerosal, has been shown to activate reversibly the inositol 1,4,5-trisphosphate (InsP(3)) receptor in several cell types. We have studied here the effects of thimerosal by monitoring the [Ca(2+)] inside the endoplasmic reticulum (ER) of intact HeLa cells with targeted aequorin. We show that thimerosal produced little effects on the ER-Ca(2+)-pump and only slightly increased the ER-Ca(2+)-leak in intact cells. Instead, thimerosal increased the sensitivity to histamine of ER-Ca(2+)-release by about two orders of magnitude, made the response much more prolonged at saturating histamine concentrations and enhanced both cytosolic and mitochondrial [Ca(2+)] responses to histamine. Moreover, inhibition of ER-Ca(2+)release by cytosolic [Ca(2+)] microdomains was fully preserved and sensitive to BAPTA-loading, and histamine-induced Ca(2+) release remained quantal in the presence of both thimerosal and intracellular BAPTA. The effects of thimerosal were reversible in the presence of dithiotreitol, suggesting the possible presence of a physiological redox regulatory mechanism. However, in permeabilized cells thimerosal potentiated InsP(3)-induced Ca(2+) release but oxidized glutathione had no effect. In addition, thimerosal increased the [Ca(2+)](ER) steady-state level in permeabilized cells. Thimerosal partially inhibited also plasma membrane Ca(2+)extrusion and increased Ca(2+)(Mn(2+)) entry through the plasma membrane, both phenomena contributing to increase the steady-state cytosolic [Ca(2+)]. Thimerosal-induced Ca(2+) entry was additive to that induced by emptying of the ER, suggesting that store-operated Ca(2+) channels may not be involved. These results provide new insights on the mechanisms of activation and inactivation of InsP(3) receptors.

  2. Suppressive effects of Hochu-ekki-to, a traditional Chinese medicine, on IgE production and histamine release in mice immunized with ovalbumin.

    PubMed

    Suzuki, T; Takano, I; Nagai, F; Fujitani, T; Ushiyama, K; Okubo, T; Seto, T; Ikeda, S; Kano, I

    1999-11-01

    We examined the effects of Bu-Zhong-Yi-Qi-Tang (Japanese name: Hochu-ekki-to, HET), a traditional Chinese medicine, on IgE production and histamine release in mice immunized intraperitoneally with a mixture of ovalbumin (OA) and aluminum hydroxide (alum adjuvant). Three groups of mice were orally administered 0, 1.7 or 17 mg of HET on day 13 after the first immunization with a mixture of 1 microg OA and 1 mg alum adjuvant. They were again immunized with the same dose of OA plus alum adjuvant on day 14. The immunological changes in mice treated with OA alone or OA plus HET were examined, and the following findings were obtained. In the HET-treated mice, the elevation of anti-OA IgE in serum, and histamine release from basophils in blood, were significantly suppressed. A significant suppression of interleukin-4 (IL-4) secretion and proliferation of splenic lymphocytes in primary culture was also observed. A tendency to suppress the elevation of anti-OA IgG1 in serum and interleukin-2 (IL-2) secretion from splenic lymphocytes was observed in the HET-treated mice. These findings suggest that oral administration of HET suppresses IgE antibody production and histamine release in type I allergic reaction in mice immunized with OA plus alum adjuvant; this shows the efficacy of HET in treating type I allergic diseases, such as asthma.

  3. Phenolic constituents of the Bangladeshi medicinal plant Pothos scandens and their anti-estrogenic, hyaluronidase inhibition, and histamine release inhibitory activities.

    PubMed

    Muhit, Md Abdul; Izumikawa, Masahiro; Umehara, Kaoru; Noguchi, Hiroshi

    2016-01-01

    Extracts from the stem and roots of the Bangladeshi medicinal plant Pothos scandens L. (Araceae) were isolated, and three hemiterpene glucoside aromatic esters, pothobanosides A (1), B (2), and C (3), and a phenylisobutanoid, pothobanol (4), along with 14 known compounds, were characterized. The isolates were tested for their estrogenic/anti-estrogenic activity using the estrogen-responsive human breast cancer cell lines MCF-7 and T47D, and syringoyl derivatives (2, 3, and canthoside B) showed strong inhibitory activity against both cell lines. Their less oxygenated analogs (1, and markhamioside F) were almost inactive. The isolates were also evaluated for hyaluronidase and histamine release inhibitory activities, and pothobanoside A (1) showed significant hyaluronidase inhibitory activity among the isolated compounds, which was similar to that of the positive control rosmarinic acid. Because hyaluronidase produces an angiogenic response that has been implicated in tumor invasiveness and metastasis, 1 could be valuable as an anti-tumor compound with a different mechanism of action from related compounds (2, 3). Pothobanoside C (3) and pothobanol (4) were also found to inhibit histamine release to a similar degree to the positive control epigallocatechin 3-O-(3"-O-methyl)-gallate. The histamine release inhibitory potency of these isolates may support the traditional uses of this plant in folk medicine. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2014-02-01

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

  5. Activation of the Na+/K(+)-pump in rat peritoneal mast cells following histamine release: a possible role in cell recovery.

    PubMed Central

    Knudsen, T.; Ferjan, I.; Johansen, T.

    1993-01-01

    1. The activity of the Na+/K(+)-pump in rat peritoneal mast cells was measured at various time intervals after induction of cellular histamine release by compound 48/80 or by the antigen-antibody reaction. The Na+/K(+)-pump activity was assessed as the ouabain-sensitive potassium uptake of the cells using 86Rb+ as a tracer for potassium (K+(86Rb+)-uptake). 2. Stimulation of the cells with compound 48/80 induced a time and concentration dependent increase of the Na+/K(+)-pump activity. The pump activity was maximal 2 min after stimulation of the cells. Then, the activity gradually decreased and reached a level not significantly different from the controls after 2 h of incubation. 3. When the cells were stimulated by the antigen-antibody reaction, there was also a rapid (within 5 min) stimulation of the Na+/K(+)-pump. In contrast to the stimulation with compound 48/80, the pump activity returned to the control level after 60 min of incubation with antigen. 4. The ouabain-resistant potassium uptake of the cells was increased after stimulation of the cells, regardless of the secretagogue used. This probably reflects the increased surface area of the cells present after the histamine release. 5. On the basis of the present results, we suggest a role for the Na+/K(+)-pump in the recovery process of the mast cell following histamine release. PMID:7679025

  6. Chemically modified tetracycline (CMT)-3 inhibits histamine release and cytokine production in mast cells: possible involvement of protein kinase C.

    PubMed

    Sandler, C; Ekokoski, E; Lindstedt, K A; Vainio, P J; Finel, M; Sorsa, T; Kovanen, P T; Golub, L M; Eklund, K K

    2005-07-01

    To find novel inhibitors of mast cell function we have studied the effect of a potent, non-antimicrobial, chemically modified tetracycline, CMT-3 or COL-3, on key functions of mast cells. In the presence of 25 microM CMT-3, the 48/80-induced histamine release from rat serosal mast cells was inhibited significantly, to 43.0 +/- 7.3% of control. Similarly, the activation-induced secretion of TNF-alpha and IL-8 by HMC-1 cells were decreased in the presence of 25 microM CMT-3 to 13.5 +/- 4.1% and 9.7 +/- 1.1% of control, respectively. CMT-3 did not cause intracellular accumulation of TNF-alpha but instead it reduced the expression of TNF-alpha mRNA in HMC-1 cells. Moreover, CMT-3 was found to significantly inhibit the protein kinase C (PKC) activity with IC(50) value of 31 microM. CMT-3 inhibited effectively both human recombinant PKCalpha and PKCdelta isoforms. In comparison to doxycycline, CMT-3 was more effective as an inhibitor of both cytokine production and PKC activity. Considering the central role of PKC in mast cell activation, PKC inhibition could, at least partially, explain the observed inhibitory effects of CMT-3. The inhibition of the key proinflammatory functions of mast cells by CMT-3 suggests its potential clinical usefulness in the treatment of allergic and inflammatory disorders.

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

    PubMed Central

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

    2010-01-01

    After oral administration, the nonimidazole histamine H3 receptor antagonist, 6-[(3-cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-N-methyl-3-pyridinecarboxamide hydrochloride (GSK189254), increased histamine release from the tuberomammillary nucleus, where all histaminergic somata are localized, and from where their axons project to the entire brain. To further understand functional histaminergic circuitry in the brain, dual-probe microdialysis was used to pharmacologically block H3 receptors in the tuberomammillary nucleus, and monitor histamine release in projection areas. Perfusion of the tuberomammillary nucleus with GSK189254 increased histamine release from the tuberomammillary nucleus, nucleus basalis magnocellularis, and cortex, but not from the striatum or nucleus accumbens. Cortical acetylcholine (ACh) release was also increased, but striatal dopamine release was not affected. When administered locally, GSK189254 increased histamine release from the nucleus basalis magnocellularis, but not from the striatum. Thus, defined by their sensitivity to GSK189254, histaminergic neurons establish distinct pathways according to their terminal projections, and can differentially modulate neurotransmitter release in a brain region-specific manner. Consistent with its effects on cortical ACh release, systemic administration of GSK189254 antagonized the amnesic effects of scopolamine in the rat object recognition test, a cognition paradigm with important cortical components. PMID:19815811

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

    SciTech Connect

    Wilson, T.; Liggins, G.C.; Aimer, G.P.; Watkins, E.J.

    1986-02-01

    Progesterone at concentrations of 10(-7)M and 10(-8)M inhibits release of (/sup 3/H)-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 (/sup 3/H)-arachidonic acid from endometrial cells by a rapid, indirect action on phospholipase activity.

  9. A COMPARISON OF THE SPECIFICITY OF INHIBITION BY PHOSPHONATE ESTERS OF THE FIRST COMPONENT OF COMPLEMENT AND THE ANTIGEN-INDUCED RELEASE OF HISTAMINE FROM GUINEA PIG LUNG

    PubMed Central

    Becker, Elmer L.; Austen, K. Frank

    1964-01-01

    The ability of a number p-nitrophenylethyl alkyl, phenyl alkyl, chloroalkyl, and aminoalkyl phosphonates to inhibit the activated first component (C'1a) of guinea pig complement, and the antigen-induced release of histamine from sliced, perfused guinea pig lung has been compared. C'1a in its reactivity with these phosphonates is distinctly more similar to trypsin than to any of the other enzymes studied previously. It is suggested that both trypsin and C'1a possess an anionic group in the active center of the respective enzyme, but the distance between the anionic and esteratic site in C'1a might be less than in trypsin. The pattern of inhibition of histamine relase by the alkyl, phenyl alkyl, and chloroalkyl phosphonates is similar to the inhibition of C'1a by these compounds, although distinct differences are apparent. The aminoalkyl phosphonates are distinctly less active inhibitors of histamine release than the corresponding alkyl phosphonates, whereas the reverse is true of the inhibition of C'1a. On the basis of these differences, it is tentatively concluded that the organophosphorus-inhibitable enzymes in the guinea pig systems studied here are similar but not identical. PMID:14212115

  10. Involvement of histamine or tumor necrosis factor in early-type hypersensitivity.

    PubMed

    Lei, H Y; Shun, C Y; Wang, J Y; Hsiue, T R; Leir, S H

    1995-03-01

    A novel early-type hypersensitivity (ETH) reaction, manifested as capillary congestion, increase of vasopermeability, and plasma protein leakage, can be induced within 1 h after challenge of antigen-sensitized mice. The mediators involved in ETH varied among different strains of mice. The poly(Glu60Ala30Tyr10) (GAT)-induced ETH in BALB/c mice was blocked by diphenhydramine (histamine H1 antagonist) and ketanserine (serotonin antagonist), but not by cimetidine (histamine H2 antagonist). These results indicate that both histamine and serotonin are involved, and that the histamine effect is mediated through a H1 receptor. Meanwhile, GAT-induced ETH in B6 mice was inhibited by anti-TNF alpha antibody suggesting that TNF alpha is involved. The mice can be classified into either histamine or TNF alpha type based on the pattern of mediator involved in ETH. A/J and CBA strains as well as BALB/c mice were classified as histamine type while A. TL, B10.BR, and C3H/He in addition to B6 mice were TNF alpha type. The observation that GAT-induced ETH in (BALB/c x B6)F1 mice was inhibited by both diphenhydramine and anti-TNF alpha suggests that the mediation of the actions of histamine or TNF alpha by GAT was genetically controlled and inherited as the dominant trait in (BALB/c x B6)F1 mice. ETH could be passively transferred by heat (56 degrees C, 4 h)-treated anti-GAT sera. Sera derived from the histamine type transferred ETH across the type barrier and histamine was the mediator, irrespective of the type of the recipient. However, sera derived from TNF alpha type only transferred ETH to the mice of the same TNF alpha type and TNF alpha was the mediator.

  11. Histamine, histamine intoxication and intolerance.

    PubMed

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

    2015-01-01

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

  12. Histamine H2-receptors on guinea-pig ileum myenteric plexus neurons mediate the release of contractile agents

    SciTech Connect

    Barker, L.A.; Ebersole, B.J.

    1982-04-01

    Dimaprit, a highly selective H2-agonist, caused a multiphasic contraction of guinea-pig ileal segments and ileal myenteric plexus-longitudinal muscle preparations. The initial phase was characterized by a twitch which reached a maximum in 15 to 30 sec and was followed by a partial relaxation. The later phase was variable and consisted of a series of twitch responses or of a slowly developing contracture which sometimes was accompanied by oscillatory changes in tension. dose-response curves were generated for the initial response; for isolated ileal segments the EC50 was 5.1 +/- 1.8 micrometers (mean +/- S.D., N . 7) and the Hill coefficient was 1.1 +/- 0.2 and for longitudinal muscle strips the EC50 was 5.8 +/- 1.2 micrometer and the Hill coefficient was 1.2 +/- 0.1 (N . 7). Both the initial and secondary components of the contractile responses to dimaprit were prevented by 0.2 micron tetrodotoxin or 10 microns mefenamic acid and by the production of tachphylaxis to either substance P or serotonin. Scopolamine, 0.001 to 0.1 micron, insurmountably antagonized only the initial component of the response. Mepyramine (1.0 micrometer), hexamethonium (100 microns), bromolysergic acid (0.25 microns) and p-(imidazol-1-yl)phenyl (10 microns) were without effect on the response to dimaprit. The histamine H2-receptor antagonist, tiotidine, produced parallel dextral shifts in the dose-response curve for dimaprit. The apparent pA2 value for tiotidine was 7.65. The results suggest that dimaprit acts on H2-receptors located on myenteric plexus neurons to cause the release of contractile substances. The mediators of the contractile response are tentatively identified as acetylcholine, substance P, serotonin and a product(s) of the arachadonic acid cascade.

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

    PubMed

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

    2015-05-01

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

  14. Recommended for release on recognizance: factors affecting pretrial release recommendations.

    PubMed

    Petee, T A

    1994-06-01

    Researchers have acknowledged the influence of pretrial release agencies in judicial decision making regarding bail; however, few researchers have focused on the process used by the pretrial release agencies to make bail-bond recommendations. In this study I sought to establish which factors were most salient in making the decision to recommend a defendant for release on recognizance. I found that both officially sanctioned release criteria and "extralegal" variables were predictive of this decision.

  15. Murine tumor necrosis factor-alpha sensitizes plasma corticosterone activity and the manifestation of shock: modulation by histamine.

    PubMed

    Hayley, Shawn; Kelly, O; Anisman, H

    2002-10-01

    Murine tumor necrosis factor-alpha (mTNF-alpha) results in the sensitization of mechanisms underlying plasma corticosterone activity and sickness behavior, the latter being reminiscent of septic or anaphylactic shock. The mTNF-alpha induced a sensitization of sickness and corticosterone in mice that was attenuated by pretreatment with the combinations of histamine H(1) (diphenhydramine, mepyramine) and H(2) (cimetidine) antagonists. Likewise, coadministration of diphenhydramine and cimetidine prevented the mTNF-alpha-provoked rise of monoamine activity within the posterior hypothalamus. Although dexamethasone ameliorated the mTNF-alpha-induced sensitization of corticosterone, illness behavior was unaffected. It is suggested that mTNF-alpha-induced illness and the neuroendocrine sensitization are mediated by endogenous histamine.

  16. Histamine and histamine receptor regulation of gastrointestinal cancers.

    PubMed

    Kennedy, Lindsey; Hodges, Kyle; Meng, Fanyin; Alpini, Gianfranco; Francis, Heather

    2012-10-01

    Histamine is a neurotransmitter released throughout the body that regulates multiple physiological responses. Primarily histamine is acknowledged for its role in inflammatory reactions to foreign pathogens that enter the body. Aside from inflammatory responses, histamine expression and synthesis has been detected in various cancer cell lines and multiple malignancies. Through experimentation histamine has demonstrated its ability to manage proliferation and angiogenesis in these cancerous cells, in either a positive or inhibitory manner. Regulation of angiogenesis and proliferation have been proven to be carried out by the stimulation or inhibition of numerous pathways and secondary response elements, such as VEGFA/C, IP3/Ca(2+), G-proteins, cAMP, and many more. The activation of these different response pathways is linked to the binding of ligands to the histamine receptors H1-H4HR. These receptors exhibit various effects dependent on whether it binds an agonist, antagonist, or its specific ligand, histamine. In cancer cell lines and different tumor cells the binding of these different compounds has shown to be one of the main components in exerting proliferative or antiproliferative changes in the microenvironment. It is also known that the histamine receptors have varying degrees of expression in different forms of cancer, and this expression can impact the tumor in various ways. This clearly indicates the significance of histamine receptors in cancer formation, and one of the aims of this review is to cover this topic concisely and in depth. Histamine is produced from numerous cells such as basophils and mast cells and is synthesized from the enzyme histidine decarboxylase (HDC). In this review we will prominently discuss the function of mast cells and HDC in histamine expression in various gastrointestinal carcinomas. We also briefly discuss current studies to support these claims. In this review we hope to give the reader a clear and comprehensible overview

  17. Histamine H4-Receptors Inhibit Mast Cell Renin Release in Ischemia/Reperfusion via Protein Kinase Cε-Dependent Aldehyde Dehydrogenase Type-2 Activation

    PubMed Central

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

    2014-01-01

    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

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

    PubMed

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

    2012-09-01

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

  19. Histamine H3 Receptor Activation Counteracts Adenosine A2A Receptor-Mediated Enhancement of Depolarization-Evoked [3H]-GABA Release from Rat Globus Pallidus Synaptosomes

    PubMed Central

    2014-01-01

    High levels of histamine H3 receptors (H3Rs) are found in the globus pallidus (GP), a neuronal nucleus in the basal ganglia involved in the control of motor behavior. By using rat GP isolated nerve terminals (synaptosomes), we studied whether H3R activation modified the previously reported enhancing action of adenosine A2A receptor (A2AR) stimulation on depolarization-evoked [3H]-GABA release. At 3 and 10 nM, the A2AR agonist CGS-21680 enhanced [3H]-GABA release induced by high K+ (20 mM) and the effect of 3 nM CGS-21680 was prevented by the A2AR antagonist ZM-241385 (100 nM). The presence of presynaptic H3Rs was confirmed by the specific binding of N-α-[methyl-3H]-histamine to membranes from GP synaptosomes (maximum binding, Bmax, 1327 ± 79 fmol/mg protein; dissociation constant, Kd, 0.74 nM), which was inhibited by the H3R ligands immepip, clobenpropit, and A-331440 (inhibition constants, Ki, 0.28, 8.53, and 316 nM, respectively). Perfusion of synaptosomes with the H3R agonist immepip (100 nM) had no effect on K+-evoked [3H]-GABA release, but inhibited the stimulatory action of A2AR activation. In turn, the effect of immepip was blocked by the H3R antagonist clobenpropit, which had no significant effect of its own on K+-induced [3H]-GABA release. These data indicate that H3R activation selectively counteracts the facilitatory action of A2AR stimulation on GABA release from striato-pallidal projections. PMID:24884070

  20. IgE and IgGa antibody-mediated release of histamine from rat peritoneal cells. II. Interaction of IgGa and IgE at the targe cell.

    PubMed

    Bach, M K; Block, K J; Austen, K F

    1971-04-01

    IgGa, in contrast to IgE, antibodies mediated the antigen-induced release of histamine from rat peritoneal mast cells without a requirement for a latent period and without the capacity to bind firmly to the target cell. Nonetheless, IgGa anti-DNP antibody interfered with the capacity of rat anti-N. brasiliensis antiserum rich in IgE antibodies to prepare the target cells for histamine release by worm antigen. Further, interaction of IgE antibody-prepared cells with IgGa anti-DNP antibody and DNP-BSA at 0 degrees C so as to achieve sterile activation, or at 30 degrees C to permit histamine release, inactivated such cells as determined by the subsequent failure to release histamine upon challenge with worm antigen. Thus, although IgE and IgGa antibodies are immunochemically distinct homologous immunoglobulins and exhibit different functional characteristics, their interaction at the target cell involves a common receptor and at least one common point in the pathway to the release of pharmacologic agents from the cell.

  1. Tumor necrosis factor-alpha release during systemic reaction in cold urticaria.

    PubMed

    Tillie-Leblond, I; Gosset, P; Janin, A; Dalenne, R; Joseph, M; Wallaert, B; Tonnel, A B

    1994-02-01

    Primary cold urticaria (PCU) characterized by the association of urticaria, angioedema, and sometimes a shock-like reaction after cold exposure, is usually considered to be linked with histamine and prostaglandin D2 release by mast cells. To determine the involvement of cytokines, we studied the release of tumor necrosis factor-alpha (TNF-alpha) in the blood of the efferent vein after immersion of the hand in chilled water. Five patients with PCU were compared with a control population (three patients with nonphysical urticaria and three healthy subjects). Among patients with PCU who underwent the cold immersion test, two exhibited a shock-like reaction with a large urticarial plaque (patients 1 and 2), one had only a mild cutaneous reaction, and two had no reaction. Patient 1 was reevaluated after 6 months of treatment with H1 and H2 antihistamines: he did not respond to this challenge. All controls were strictly negative. Histamine was released within the first minute after the challenge in the three patients with PCU, but at a higher level for the two patients who had a systemic reaction. TNF-alpha was undetectable in the blood of the patient with only a mild cutaneous reaction, whereas TNF-alpha release was observed for the two patients with a systemic reaction, 2 and 6 minutes after the end of the cold immersion test. The two other patients and the control subjects released neither histamine nor TNF-alpha. In parallel, pathologic and immunohistochemical (with a rabbit anti-TNF-alpha antibody) studies were performed on skin biopsy specimens collected 10 minutes after ice-cube test.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. In vitro inhibition of histamine release behavior of cetirizine intercalated into Zn/Al- and Mg/Al-layered double hydroxides.

    PubMed

    Hussein-Al-Ali, Samer Hasan; Al-Qubaisi, Mothanna; Hussein, Mohd Zobir; Ismail, Maznah; Zainal, Zulkarnain; Hakim, Muhammad Nazrul

    2012-01-01

    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.

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

    PubMed Central

    Hussein-Al-Ali, Samer Hasan; Al-Qubaisi, Mothanna; Hussein, Mohd Zobir; Ismail, Maznah; Zainal, Zulkarnain; Hakim, Muhammad Nazrul

    2012-01-01

    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. PMID:22754339

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

    PubMed

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

    2013-09-27

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

  5. GROA AIRBORNE RELEASE DISPERSION FACTOR CALCULATION

    SciTech Connect

    J. Wang

    2005-03-21

    The purpose of this document is to calculate airborne release dispersion factors ({chi}/Q) for the surface and subsurface facilities at the Geological Repository Operations Area (GROA). The calculated {chi}/Q values may be used to estimate radiological consequences to workers for potential releases from normal operations and event sequences for License Application. The scope of this document is to provide estimates of {chi}/Q values at potential onsite receptors from facility releases, under normal operating conditions and event sequences.

  6. Activation of histamine H3-receptors inhibits carrier-mediated norepinephrine release during protracted myocardial ischemia. Comparison with adenosine A1-receptors and alpha2-adrenoceptors.

    PubMed

    Imamura, M; Lander, H M; Levi, R

    1996-03-01

    We previously showed that prejunctional histamine H3-receptors downregulate norepinephrine exocytosis, which is markedly enhanced in early myocardial ischemia. In the present study, we investigated whether H3-receptors modulate nonexocytotic norepinephrine release during protracted myocardial ischemia. In this setting, decreased pH(i) in sympathetic nerve endings sequentially leads to a compensatory activation of the Na+-H+ antiporter (NHE), accumulation of intracellular Na+, reversal of the neuronal uptake of norepinephrine, and thus carrier-mediated release of norepinephrine. Accordingly, norepinephrine overflow from isolated guinea pig hearts undergoing 20-minute global ischemia and 45-minute reperfusion was attenuated approximately 80% by desipramine (10 nmol/L) and 70% by 5-(N-ethyl-N-isopropyl)-amiloride (EIPA, 10 micromol/L), inhibitors of norepinephrine uptake and NHE, respectively. The H3-receptor agonist imetit (0.1 micromol/L) decreased carrier-mediated norepinephrine release by approximately 50%. This effect was blocked by the H3-receptor antagonist thioperamide (0.3 micromol/L), indicating that H-receptor activation inhibits carrier-mediated norepinephrine release. At lower concentrations, imetit (10 nmol/L) or EIPA (3 micromol/L) did not inhibit carrier-mediated norepinephrine release. However, a 25% inhibition occurred with imetit (10 nmol/L) and EIPA (3 micromol/L) combined. This synergism suggests an association between H-receptors and NHE. Conceivably, activation of H-receptors may lead to inhibition of NHE. In fact, alpha2-adrenoceptor activation, which is known to stimulate NHE, enhanced norepinephrine release, whereas alpha2-adrenoceptor blockade attenuated it. Furthermore, activation of adenosine A1-receptors markedly attenuated norepinephrine release, whereas their inhibition potentiated it. Because norepinephrine directly correlated with the severity of reperfusion arrhythmia and imetit reduced the incidence of ventricular fibrillation by 50

  7. Inhibition of granulation tissue growth by histamine.

    PubMed

    Saeki, K; Yokoyama, J; Wake, K

    1975-06-01

    Granulomas were induced in rats by subcutaneous implantation of formalin-soaked filter-paper disks. Daily subcutaneous injection of histamine at doses of two times 0.05 mg/kg and above inhibited the growth of granulation tissue as measured by a marked decrease in the dry-defatted granuloma weight and of the hydroxyproline and hexosamine content. Histological observations of granulation tissue indicated that histamine inhibited the proliferation of fibroblasts and the formation of capillaries. Inhibitory effects were also observed with the histamine releaser, sinomenine, and the histaminase inhibitor, aminoguanidine. These histamine effects seem not to be mediated by glucocorticoid release, since an effective dose level of histamine produced no change in growth or thymus weight. Prednisolone was less potent than histamine in inhibiting Prednisolone was ineffective at the dose tested. Subcutaneous injection of the H2-receptor antagonist, burimamide, blocked these histamine effects and also of sinomeinine and aminoguanidine. The H1-receptor antagonist, mepyramine, did not block these histamine effects. Burimamide alone enhanced the growth of granuloma. These results indicate that granulation-tissue growth in inflammation is affected by the inhibitory effect of endogenous histamine acting through H2-receptors.

  8. Gender-related effects of sex steroids on histamine release and FcεRI expression in rat peritoneal mast cells.

    PubMed

    Muñoz-Cruz, Samira; Mendoza-Rodríguez, Yolanda; Nava-Castro, Karen E; Yepez-Mulia, Lilián; Morales-Montor, Jorge

    2015-01-01

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

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

    PubMed Central

    Muñoz-Cruz, Samira; Mendoza-Rodríguez, Yolanda; Nava-Castro, Karen E.; Yepez-Mulia, Lilián; Morales-Montor, Jorge

    2015-01-01

    Mast cells (MCs) are versatile effector and regulatory cells in various physiologic, immunologic, and pathologic processes. In addition to the well-characterized IgE/FcεRI-mediated degranulation, a variety of biological substances can induce MCs activation and release of their granule content. Sex steroids, mainly estradiol and progesterone, have been demonstrated to elicit MCs activation. Most published studies have been conducted on MCs lines or freshly isolated peritoneal and bone marrow-derived MC without addressing gender impact on MC response. Our goal was to investigate if the effect of estradiol, progesterone, testosterone, and dihydrotestosterone (DHT) on MCs may differ depending on whether female or male rats are used as MCs donors. Our results demonstrated that effect of sex steroids on MCs histamine release is dose- and gender-dependent and can be direct, synergistic, or inhibitory depending on whether hormones are used alone or to pretreat MCs followed by substance P-stimulation or upon IgE-mediated stimulation. In contrast, sex steroids did not have effect on the MC expression of the IgE high affinity receptor, FcεRI, no matter female or male rats were used. In conclusion, MCs degranulation is modulated by sex hormones in a gender-selective fashion, with MC from females being more susceptible than MC from males to the effects of sex steroids. PMID:25973435

  10. Dust from carpeted and smooth floors. V. Cat (Fel d I) and mite (Der p I and Der f I) allergen levels in school dust. Demonstration of the basophil histamine release induced by dust from classrooms.

    PubMed

    Dybendal, T; Elsayed, S

    1992-12-01

    Sixty dust samples from schools in Norway were analysed for major allergens from cat and mite after sampling with the regularly used vacuum cleaners for 5 days and with a new model vacuum cleaner for 10 days, respectively. The major feline allergen Felis domesticus allergen I (Fel d I) was detected in all the classrooms, with ranges from 12 to 16,840 ng/m2 floor area. The mean Fel d I concentration was about 11 times higher per unit area carpeted floors as compared with smooth floors after the 10 days sampling period. Mite allergens Dermatophagoides pteronyssinus allergen I (Der p I) and Dermatophagoides farinae allergen I (Der f I) were detected in very low concentrations, with ranges from < 1 ng to 104 ng/m2 floor area. These findings suggest that the school is a protective environment against mite infestation, while the prevalence of cat allergens in classrooms seems higher than previously assumed. Basophil histamine release was measured after provocation with 20 dust extracts from 10 different schools. In nine of the 10 schools examined, the basophil histamine release caused by challenge with carpet dust was higher than the corresponding release with smooth floor dust. The calculated floor areas in each school in which dust led to 15% histamine release were from 2 to 55 times larger for smooth floors compared with carpeted floors. These results emphasize previous findings regarding higher allergen concentrations in classrooms with carpeted floors.

  11. Endothelial and smooth muscle histamine receptors

    SciTech Connect

    Blank, R.S.; Hollis, T.M.

    1986-03-01

    Histamine is produced within the vascular wall and mediates a variety of normal and pathologic vascular responses. The interaction of histamine with its vascular cell receptors has been shown to affect factors such as actin cable formation, cyclase activities, prostacyclin synthesis, cell motility, and proliferation. In addition, abundant evidence exists to implicate an arterial nascent histamine pool in the control of vessel wall permeability under conditions of stress and injury. However, endothelial and smooth muscle cell histamine receptors have been only incompletely characterized. The authors report here the time-dependent, saturable, and trypsin sensitive binding of /sup 3/H-histamine to the endothelial cell surface. The K/sub d/ for endothelial and smooth muscle cell histamine receptors are 0.70 and 2.80 ..mu..M respectively. Histamine binding to smooth muscle cells also exhibited saturation with concentrations of /sup 3/H-histamine up to 4 ..mu..M. While the smooth muscle cell H/sub 1/ receptor binding was negligible, the H/sub 2/ receptor appeared to represent a relatively low affinity, high capacity site for histamine binding. The uptake of /sup 3/H-histamine in both cell types displayed kinetics consistent with that of fluid-phase pinocytosis.

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

    PubMed

    van Ree, R; Aalberse, R C

    1995-03-01

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

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

    PubMed

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

    2017-03-15

    Ciproxifan is an H3 receptor antagonist and inverse agonist with antipsychotic effects in several preclinical models; its effect on glutamate release has been investigated in the rat hippocampus. In a synaptosomal preparation, ciproxifan reduced 4-aminopyridine (4-AP)-evoked Ca(2+)-dependent glutamate release and cytosolic Ca(2+) concentration elevation but did not affect the membrane potential. The inhibitory effect of ciproxifan on 4-AP-evoked glutamate release was prevented by the Gi/Go-protein inhibitor pertussis toxin and Cav2.2 (N-type) and Cav2.1 (P/Q-type) channel blocker ω-conotoxin MVIIC, but was not affected by the intracellular Ca(2+)-release inhibitors dantrolene and CGP37157. Furthermore, the phospholipase A2 (PLA2) inhibitor OBAA, prostaglandin E2 (PGE2), PGE2 subtype 2 (EP2) receptor antagonist PF04418948, and extracellular signal-regulated kinase (ERK) inhibitor FR180204 eliminated the inhibitory effect of ciproxifan on glutamate release. Ciproxifan reduced the 4-AP-evoked phosphorylation of ERK and synapsin I, a presynaptic target of ERK. The ciproxifan-mediated inhibition of glutamate release was prevented in synaptosomes from synapsin I-deficient mice. Moreover, ciproxifan reduced the frequency of miniature excitatory postsynaptic currents without affecting their amplitude in hippocampal slices. Our data suggest that ciproxifan, acting through the blockade of Gi/Go protein-coupled H3 receptors present on hippocampal nerve terminals, reduces voltage-dependent Ca(2+) entry by diminishing PLA2/PGE2/EP2 receptor pathway, which subsequently suppresses the ERK/synapsin I cascade to decrease the evoked glutamate release.

  14. Histamine release by exocytosis from rat mast cells on reduction of extracellular sodium: a secretory response inhibited by calcium, strontium, barium or magnesium.

    PubMed Central

    Cochrane, D E; Douglas, W W

    1976-01-01

    1. Histamine release from peritoneal mast cells of the rat was stimulated when the cells were exposed for 10 min to sodium-deficient media where all NaCl had been replaced by KC1, RbC1, glucose, sucrose, mannitol, or Tris, provided calcium was less than about 0-5 mM. 2. Light and electron microscopy showed the response to be exocytosis. 3. The chelating agents, EDTA and EGTA, abolished the response to sodium lack and their inhibitory effects were reversed by re-incubating cells with calcium but not magnesium. 4. The response was inhibited by dinitrophenol combined with glucose-deprivation. 5. The response was inversely related to the concentrations of sodium and calcium below 137-5 and 0-5 mM respectively. 6. The related alkaline earth metals, barium, strontium, and magnesium, resembled calcium in inhibiting the response to sodium lack. 7. No secretory response was seen when the cells were exposed for 10 min to calcium-free medium in which lithium replaced sodium. Exposure to this medium for 60 min, however, elicited secretion. 8. It is concluded that when extracellular calcium is low, a reduction in extracellular sodium induces a conventional exocytotic secretory response dependent on energy and cellular calcium. It is suggested that sodium lack may mobilize calcium from a cellular site possibly the inner aspect of the plasma membrane. Images A B C D E F G H PMID:59804

  15. Rupatadine inhibits inflammatory mediator release from human laboratory of allergic diseases 2 cultured mast cells stimulated by platelet-activating factor.

    PubMed

    Alevizos, Michail; Karagkouni, Anna; Vasiadi, Magdalini; Sismanopoulos, Nikolaos; Makris, Michael; Kalogeromitros, Dimitrios; Theoharides, Theoharis C

    2013-12-01

    Mast cells are involved in allergy and inflammation by the secretion of multiple mediators, including histamine, cytokines, and platelet-activating factor (PAF), in response to different triggers, including emotional stress. PAF has been associated with allergic inflammation, but there are no clinically available PAF inhibitors. To investigate whether PAF could stimulate human mast cell mediator release and whether rupatadine (RUP), a dual histamine-1 and PAF receptor antagonist, could inhibit the effect of PAF on human mast cells. Laboratory of allergic diseases 2 cultured mast cells were stimulated with PAF (0.001, 0.01, and 0.1 μmol/L) and substance P (1 μmol/L) with or without pretreatment with RUP (2.5 and 25 μmol/L), which was added 10 minutes before stimulation. Release of β-hexosaminidase was measured in supernatant fluid by spectrophotoscopy, and histamine, interleukin-8, and tumor necrosis factor were measured by enzyme-linked immunosorbent assay. PAF stimulated a statistically significant release of histamine, interleukin-8, and tumor necrosis factor (0.001-0.1 μmol/L) that was comparable to that stimulated by substance P. Pretreatment with RUP (25 μmol/L) for 10 minutes inhibited this effect. In contrast, pretreatment of laboratory of allergic diseases 2 cells with diphenhydramine (25 μmol/L) did not inhibit mediator release, suggesting that the effect of RUP was not due to its antihistaminic effect. PAF stimulates human mast cell release of proinflammatory mediators that is inhibited by RUP. This action endows RUP with additional properties in treating allergic inflammation. Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  16. Co-axial bioassay of a smooth muscle relaxant factor released from guinea-pig tracheal epithelium.

    PubMed

    Fernandes, L B; Paterson, J W; Goldie, R G

    1989-01-01

    1. The ability of guinea-pig trachea to release an epithelium-derived relaxant factor (EpDRF) was assessed in a co-axial bioassay system. 2. Histamine (100 microM) and methacholine (25 microM) caused endothelium-dependent relaxation of rat isolated aorta, presumably via the release of endothelium-derived relaxant factor (EDRF). In contrast, endothelium-denuded rat aorta did not relax in response to these agents. 3. EDRF release was detected in response to methacholine in a co-axial bioassay system, consisting of intact rabbit aorta tube (EDRF donor) and endothelium-denuded rat aorta strip (assay preparation). These results indicated the transfer of EDRF from a donor to an assay preparation, thereby validating the co-axial bioassay method. 4. Substitution of endothelium-intact rabbit aorta tube by epithelium-intact guinea-pig tracheal tube tissue in co-axial assemblies, still allowed the assay preparation to relax in response to histamine or methacholine. Removal of the intact tracheal tube from the system, or removal of the epithelium from the donor tracheal tube in co-axial preparations, abolished such relaxant responses. These observations are consistent with histamine- or methacholine-induced release of an epithelium-derived relaxant factor (EpDRF) from the trachea. 5. In the co-axial assembly comprising intact guinea-pig trachea and endothelium-denuded rat aorta, histamine and methacholine produced concentration-dependent, EpDRF-induced aortic relaxation. Mean concentrations of histamine and methacholine producing 50% of the maximum relaxation (EC50) were 39.8 microM and 2.7 microM respectively. Histamine-induced relaxation was inhibited in the presence of mepyramine (2 microM) and responses to methacholine were inhibited by atropine (0.1 microM). 6. Methylene blue (50 microM) had no effect on such relaxant responses, indicating that EpDRF does not activate guanylate cyclase. Furthermore, the cyclo-oxygenase inhibitor indomethacin (5 microM), the cyclo

  17. The influence of cholinergic agents on histamine release from HMC-1 human mast cell line stimulated with IgG, C-reactive protein and compound 48/80.

    PubMed

    Nazarov, Peter G; Pronina, Anastasia P

    2012-11-27

    The aim of this work is to study the role of acetylcholine (ACh) receptors (AChRs) in the regulation of FcγR activity in human mast cells (MC) activated by aggregated IgG (aIgG) and CRP. MC, the key regulators at the interface of innate and acquired immunity, have abundant Fc receptors for IgG (FcγRII) which indicate the role of their ligands, IgG and C-reactive protein (CRP), in regulating MC activity. Cholinergic control of FcγR-dependent MC functions is poorly defined. HMC-1 culture of human MC; cell incubations with cholinergic drugs and FcγR ligands such as heat aggregated human IgG or purified human CRP; compound 48/80, a known histamine liberator employing G protein-coupled receptors, was used as a positive control of MC degranulation; assessment of histamine release. Both nAChR and mAChR antagonists (hexamethonium and methacine, respectively), per se, elevated histamine-releasing activity of the HMC-1 and suppressed the MC responses to most of investigated activators (carbachol, compound 48/80, and to a lesser extent aIgG). Two blockers together should be applied to aIgG-stimulated cells in order to obtain appreciable suppression of histamine release. The FcγR-mediated HMC-1 cell response to CRP was the least sensitive to attenuation by ACh signaling. The data obtained suggest the involvement of ACh in the functioning of other receptor systems. Our results indicate that AChRs are closely associated with G protein-coupled receptor-induced reactions of MC and optionally with FcγR-dependent functions. The data presented demonstrate that AChRs and endogenous ACh are involved in regulating mast cell degranulation and histamine release by affecting the functions of receptors to compound 48/80 and, less, FcγRs. Copyright © 2012 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2014-10-01

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

  19. Fusion of Na-ASP-2 with human immunoglobulin Fcγ abrogates histamine release from basophils sensitized with anti-Na-ASP-2 IgE.

    PubMed

    Zhan, Bin; Santiago, H; Keegan, B; Gillespie, P; Xue, J; Bethony, J; de Oliveira, L M; Jiang, D; Diemert, D; Xiao, S-H; Jones, K; Feng, X; Hotez, P J; Bottazzi, M E

    2012-01-01

    Na-ASP-2 is a major protein secreted by infective third-stage larvae (L3) of the human hookworm Necator americanus upon host entry. It was chosen as a lead vaccine candidate for its ability to elicit protective immune responses. However, clinical development of this antigen as a recombinant vaccine was halted because it caused allergic reactions among some of human volunteers previously infected with N. americanus. To prevent IgE-mediated allergic reactions induced by Na-ASP-2 but keep its immunogenicity as a vaccine antigen, we designed and tested a genetically engineered fusion protein, Fcγ/Na-ASP-2, composed of full-length Na-ASP-2 and truncated human IgG Fcγ1 that targets the negative signalling receptor FcγRIIb expressed on pro-allergic cells. The chimeric recombinant Fcγ/Na-ASP-2 protein was expressed in Pichia pastoris and shared the similar antigenicity as native Na-ASP-2. Compared to Na-ASP-2, the chimeric fusion protein efficiently reduced the release of histamine in human basophils sensitized with anti-Na-ASP-2 IgE obtained from individuals living in a hookworm-endemic area. In dogs infected with canine hookworm, Fcγ/Na-ASP-2 resulted in significantly reduced immediate-type skin reactivity when injected intradermally compared with Na-ASP-2. Hamsters vaccinated with Fcγ/Na-ASP-2 formulated with Alhydrogel(®) produced specific IgG that recognized Na-ASP-2 and elicited similar protection level against N. americanus L3 challenge as native Na-ASP-2.

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

    PubMed

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

    1998-08-01

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

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

    PubMed

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

    2013-02-08

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

  2. Modulatory effects of histamine on cat carotid body chemoreception.

    PubMed

    Del Rio, Rodrigo; Moya, Esteban A; Koenig, Cecilia S; Fujiwara, Kunio; Alcayaga, Julio; Iturriaga, Rodrigo

    2008-12-31

    Histamine has been proposed to be an excitatory transmitter between the carotid body (CB) chemoreceptor (glomus) cells and petrosal ganglion (PG) neurons. The histamine biosynthetic pathway, its storage and release, as well as the presence of histamine H1, H2 and H3 receptors have been found in the CB. However, there is only indirect evidence showing the presence of histamine in glomus cells, or weather its application produces chemosensory excitation. Thus, we studied the histamine immunocytochemical localization in the cat CB, and the effects of histamine, and H1, H2 and H3 receptor blockers on carotid sinus nerve (CSN) discharge, using CB and PG preparations in vitro. We found histamine immunoreactivity in dense-cored vesicles of glomus cells. Histamine induced dose-dependent increases in CSN discharge in the CB, but not in the PG. The H1-antagonist pyrilamine reduced the CB responses induced by histamine, the H2-antagonists cimetidine and ranitidine had no effect, while the H3-antagonist thioperamide enhanced histamine-induced responses. Present data suggests that histamine plays an excitatory modulatory role in the generation of cat CB chemosensory activity.

  3. Neutrophil histamine contributes to inflammation in mycoplasma pneumonia

    PubMed Central

    Xu, Xiang; Zhang, Dongji; Zhang, Hong; Wolters, Paul J.; Killeen, Nigel P.; Sullivan, Brandon M.; Locksley, Richard M.; Lowell, Clifford A.; Caughey, George H.

    2006-01-01

    Mycoplasmas cause chronic inflammation and are implicated in asthma. Mast cells defend against mycoplasma infection and worsen allergic inflammation, which is mediated partly by histamine. To address the hypothesis that mycoplasma provokes histamine release, we exposed mice to Mycoplasma pulmonis, comparing responses in wild-type and mast cell–deficient KitW-sh/KitW-sh (W-sh) mice. Low histamine levels in uninfected W-sh mice confirmed the conventional wisdom that mast cells are principal sources of airway and serum histamine. Although mycoplasma did not release histamine acutely in wild-type airways, levels rose up to 50-fold above baseline 1 week after infection in mice heavily burdened with neutrophils. Surprisingly, histamine levels also rose profoundly in infected W-sh lungs, increasing in parallel with neutrophils and declining with neutrophil depletion. Furthermore, neutrophils from infected airway were highly enriched in histamine compared with naive neutrophils. In vitro, mycoplasma directly stimulated histamine production by naive neutrophils and strongly upregulated mRNA encoding histidine decarboxylase, the rate-limiting enzyme in histamine synthesis. In vivo, treatment with antihistamines pyrilamine or cimetidine decreased lung weight and severity of pneumonia and tracheobronchitis in infected W-sh mice. These findings suggest that neutrophils, provoked by mycoplasma, greatly expand their capacity to synthesize histamine, thereby contributing to lung and airway inflammation. PMID:17158962

  4. Human adipocytes secrete mineralocorticoid-releasing factors.

    PubMed

    Ehrhart-Bornstein, M; Lamounier-Zepter, V; Schraven, A; Langenbach, J; Willenberg, H S; Barthel, A; Hauner, H; McCann, S M; Scherbaum, W A; Bornstein, S R

    2003-11-25

    Obesity has become an epidemic problem in western societies, contributing to metabolic diseases, hypertension, and cardiovascular disease. Overweight and obesity are frequently associated with increased plasma levels of aldosterone. Recent evidence suggests that human fat is a highly active endocrine tissue. Therefore, we tested the hypothesis that adipocyte secretory products directly stimulate adrenocortical aldosterone secretion. Secretory products from isolated human adipocytes strongly stimulated steroidogenesis in human adrenocortical cells (NCI-H295R) with a predominant effect on mineralocorticoid secretion. Aldosterone secretion increased 7-fold during 24 h of incubation. This stimulation was comparable to maximal stimulation of these cells with forskolin (2 x 10(-5) M). On the molecular level, there was a 10-fold increase in the expression of steroid acute regulatory peptide mRNA. This effect was independent of adipose angiotensin II as revealed by the stimulatory effect of fat cell-conditioned medium even in the presence of the angiotensin type 1 receptor antagonist, valsartan. None of the recently defined adipocytokines accounted for the effect. Mineralocorticoid-stimulating activity was heat sensitive and could be blunted by heating fat cell-conditioned medium to 99 degrees C. Centrifugal filtration based on molecular mass revealed at least two releasing factors: a heat sensitive fraction (molecular mass >50 kDa) representing 60% of total activity, and an inactive fraction (molecular mass <50 kDa). However, the recovery rate increased to 92% when combining these two fractions, indicating the interaction of at least two factors. In conclusion, human adipocytes secrete potent mineralocorticoid-releasing factors, suggesting a direct link between obesity and hypertension.

  5. The hypophagic factor oleoylethanolamide differentially increases c-fos expression in appetite regulating centres in the brain of wild type and histamine deficient mice.

    PubMed

    Umehara, Hayato; Fabbri, Roberta; Provensi, Gustavo; Passani, M Beatrice

    2016-11-01

    Histaminergic neurons in the hypothalamic tuberomamillary nucleus (TMN) establish connections with virtually all brain areas. Recent evidence suggests that feeding-related motivation is correlated with the activation of a subpopulation of histamine neurons in the ventral TMN that project to hypothalamic and subcortical areas controlling feeding behaviour. Oleoylethanolamide (OEA) is a hypophagic lipid-amide released by the small intestine in response to daily fat intake that indirectly activates hypothalamic oxytocin-neurons in the paraventricular (PVN) and supraoptic (SON) nuclei. We recently showed that OEA requires the integrity of neuronal histamine to fully display its hypophagic effect. Here we aimed to investigate if differences exist in OEA-induced c-Fos expression in several brain regions of fasted, histidine decarboxylase (HDC)-KO mice that do not synthesize histamine, and wild type (WT) littermates. All the brain regions examined receive histaminergic innervation and are involved in different aspects of feeding behaviour. We found that OEA increased c-Fos expression in the SON, arcuate nucleus (ARC) and the amygdala of WT mice, but not HDC-KO mice, whereas neither genotype nor treatment differences were observed in the lateral and dorsomedial hypothalamus. Furthermore, oxytocin-immunostaining was markedly increased in the neurohypophysis of WT and not in HDC-KO mice. Of note, OEA increased c-Fos expression in the nucleus of solitary tract of both genotypes. Our findings suggest that the TMN serves as a relay station to elaborate peripheral signals that control homeostatic and adaptive behavioural responses. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    DTIC Science & Technology

    1992-01-01

    bacitracin . variations it response remain inexplicable. bestatimt. compouind 48/80 andl histamine diphos- In thtis report. tlte actiont of netirokinlins...Actions 26, 11-). deries iias cel lut aid isthe irs to huiwtha lOe.tiluer 11- Iwprapuii Z-, Reniun. N. aniid Regoli. I). derives~~~~~~ ~ ~ matcl i adi

  7. Central corticotropin releasing factor and social stress

    PubMed Central

    Backström, Tobias; Winberg, Svante

    2013-01-01

    Social interactions are a main source of stress in vertebrates. Social stressors, as well as other stressors, activate the hypothalamic–pituitary–adrenal (HPA) axis resulting in glucocorticoid release. One of the main components of the HPA axis is corticotropin releasing factor (CRF). The neuropeptide CRF is part of a peptide family including CRF, urocortin 1–3, urotensin 1–3, and sauvagine. The actions of the CRF family are mediated by at least two different receptors with different anatomical distribution and affinities for the peptides. The CRF peptides affect several behavioral and physiological responses to stress including aggression, feeding, and locomotor activity. This review will summarize recent research in vertebrates concerning how social stress interacts with components of the CRF system. Consideration will be taken to the different models used for social stress ranging from social isolation, dyadic interactions, to group dominance hierarchies. Further, the temporal effect of social stressor from acute, intermittent, to chronic will be considered. Finally, strains selected for specific behavior or physiology linked to social stress will also be discussed. PMID:23847465

  8. Prostaglandin E2 Inhibits Histamine-Evoked Ca2+ Release in Human Aortic Smooth Muscle Cells through Hyperactive cAMP Signalling Junctions and Protein Kinase A.

    PubMed

    Taylor, Emily J A; Pantazaka, Evangelia; Shelley, Kathryn L; Taylor, Colin W

    2017-09-06

    In human aortic smooth muscle cells (ASMC), prostaglandin E2 (PGE2) stimulates adenylyl cyclase (AC) and attenuates the increase in intracellular free Ca(2+) concentration ([Ca(2+)]i) evoked by activation of histamine H1 receptors. The mechanisms are not resolved. We show that cAMP mediates inhibition of histamine-evoked Ca(2+) signals by PGE2 Exchange proteins activated by cAMP (EPACs) were not required, but the effects were attenuated by inhibition of cAMP-dependent protein kinase (PKA). PGE2 had no effect on the Ca(2+) signals evoked by protease-activated receptors, heterologously expressed muscarinic M3 receptors, or by direct activation of inositol 1,4,5-trisphosphate (IP3) receptors by photolysis of caged IP3 The rate of Ca(2+) removal from the cytosol was unaffected by PGE2, but PGE2 attenuated histamine-evoked IP3 accumulation. Substantial inhibition of AC had no effect on the concentration-dependent inhibition of Ca(2+) signals by PGE2 or butaprost (to selectively activate EP2 receptors), but it modestly attenuated responses to EP4 receptors, activation of which generated less cAMP than EP2 receptors. We conclude that inhibition of histamine-evoked Ca(2+) signals by PGE2 occurs through 'hyperactive signalling junctions', wherein cAMP is locally delivered to PKA at super-saturating concentrations to cause uncoupling of H1 receptors from phospholipase C. This sequence allows digital signalling from PGE2 receptors, through cAMP and PKA, to histamine-evoked Ca(2+) signals. The American Society for Pharmacology and Experimental Therapeutics.

  9. High-dose anti-histamine use and risk factors in children with urticaria

    PubMed Central

    Uysal, Pınar; Avcil, Sibelnur; Erge, Duygu

    2016-01-01

    Aim The drugs of choice in the treatment of urticaria in children are H1-antihistamines. The aim of the study was to evaluate children with urticaria and define risk factors for requirement of high-dose H1-antihistamines in children with urticaria. Material and Methods The medical data of children who were diagnosed as having urticaria admitted to our outpatient clinic between January 2014 and January 2016 were searched. The medical histories, concomitant atopic diseases, parental atopy histories, medications, treatment responses, blood eosinophil and basophil counts, and serum total IgE levels were recorded. In addition, the urticaria activity score for seven days, autoimmune antibody tests, and skin prick test results were evaluated in children with chronic urticaria. Results The numbers of the children with acute and chronic urticaria were 138 and 92, respectively. The age of the children with chronic urticaria was higher than that of those with acute urticaria (p<0.0001). There was no difference between the two groups in terms of blood eosinophil and basophil counts, and serum total IgE levels (p>0.05). There was a negative correlation between blood eosinophil count and the UAS7 score in children with chronic urticaria (r=−0.276, p=0.011). Chronic urticaria and requirement of high dose H1-antihistamines were significant in children aged ≥10 years (p<0.001, p=0.015). High UAS7 score (OR: 1.09; CI 95%: [1.03–1.15]) and basopenia (OR: 6.77; CI 95%: [2.01–22.75]) were associated with the requirement of high-dose H1-AH in children with chronic urticaria. Conclusion The requirement of high-dose H1-antihistamines was higher with children’s increasing age. Disease severity and basopenia were risk factors for the requirement of high-dose H1-antihistamines. PMID:28123332

  10. The protein kinase MEK1/2 mediate vascular endothelial growth factor- and histamine-induced hyperpermeability in porcine coronary venules

    PubMed Central

    Wu, Mack H; Yuan, Sarah Y; Granger, Harris J

    2005-01-01

    Mitogen-activated protein kinases (MAPKs) have been implicated in the signal transduction of the endothelial response to growth factors and inflammatory stimuli. The objective of this study was to test the hypothesis that the p42/44 MAPK pathway plays a common role in mediating the microvascular hyperpermeability response to vascular endothelial growth factor (VEGF) and histamine. The apparent permeability coefficient of albumin was measured in isolated and perfused coronary venules. Application of VEGF induced a rapid increase in venular permeability, and the effect was blocked by PD98059 and UO126, selective inhibitors of the mitogen-activated protein kinase kinase MEK1/2, in a dose-dependent pattern. The same MEK1/2 inhibitors dose-dependently attenuated the increase in venular permeability caused by histamine. In addition, the increases in venular permeability caused by agents that are known to activate the nitric oxide pathway, including the calcium ionophore ionomycin, the nitric oxide donor S-nitroso-N-acetylpenicillamine, and the protein kinase G activator 8-bromo-cGMP, were significantly attenuated in venules pretreated with the MEK1/2 inhibitors. Furthermore, transfection of venules with active MEK1 increased baseline permeability. In contrast, transfection of active ERK1, a downstream target of MEK1/2, did not significantly alter the basal permeability of venules. Moreover, inhibition of ERK1/2 with a specific inhibiting peptide did not prevent the hyperpermeability response to VEGF or histamine. The results suggest that activation of MEK1/2 may play a central role in the signal transduction of microvascular hyperpermeability in response to growth factors and inflammatory mediators. PMID:15539400

  11. Adrenergic and cromolyn sodium modulation of ECL cell histamine secretion.

    PubMed

    Lawton, G P; Tang, L H; Miu, K; Gilligan, C J; Absood, A; Modlin, I M

    1995-01-01

    The histamine secreting enterochromaffin-like (ECL) cell is now recognized as the principal regulator of gastric acid secretion. Histamine is not only a primary modulator of acid secretion, but may be of relevance in gastritis and as a mitogen in gastric neoplasia. Study of the ECL cell has been limited since no pure preparation was available. We therefore developed a pure isolated ECL cell preparation with a purity of 90-95% as determined by total histamine content and chromogranin immunofluorescence. Trypan blue exclusion demonstrated > 95% viability. While gastrin and acetylcholine are known modulators of acid secretion, the role of adrenergic neurotransmitters has not been clearly delineated. The purpose of this study was to examine adrenergic modulation of ECL cell histamine release. To further define the inhibitory mechanisms of histamine secretion, we evaluated the mast cell histamine inhibitor sodium cromoglycate. Histamine secretion was determined by radioimmunoassay. Basal secretion was 0.6 +/- 0.2 nmol/10(3) cells. Gastrin stimulated histamine secretion with an EC50 of 3 x 10(-10) M. Octopamine (alpha-adrenergic agonist) (10(-11)-10(-4) M) failed to stimulate histamine secretion. Isoproterenol (beta-adrenergic agonist) stimulated histamine secretion (EC50, 6 x 10(-8) M) and was inhibited by propranolol (IC50 5 x 10(-10) M).(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Factors controlling gastric-glucagon release.

    PubMed Central

    Lefèbvre, P J; Luyckx, A S

    1977-01-01

    A system consisting of an isolated dog stomach perfused with whole blood has been designed to study gastric glucagon secretion. Under basal conditions, gastric glucagon release was 0.0-3.1 ng glucagon/100g of stomach per min. Arginine, at an arterial plasma concentration averaging 10 mM, elicited a rapid glucagon release. This gastric glucagon release was almost completely abolished by somatostatin (100 ng/ml). The release of gastric glucagon was not affected by hyperglycemia alone but was reduced by about 40% when hyperglycemia was concomitant with an hyperinsulinemia within the physiological range. These observations support the concept that adequate concentrations of insulin are necessary in order for hyperglycemia to inhibit gastric glucagon secretion. Furthermore, it is suggested that the isolated perfused dog stomach might provide a unique tool permitting investigation of alpha-cell function in the absence of endogenously released insulin. PMID:845258

  13. Mental illness, criminal risk factors and parole release decisions.

    PubMed

    Matejkowski, Jason; Draine, Jeffrey; Solomon, Phyllis; Salzer, Mark S

    2011-01-01

    Research has not examined whether higher rates of parole denial among inmates with mental illness (MI) are the result of the increased presence of criminal risk factors among this population. Employing a representative sample of inmates with (n  =  219) and without (n  =  184) MI receiving parole release decisions in 2007, this study tested whether the central eight risk factors for recidivism considered in parole release decisions intervened in the relationship between MI and parole release. MI was associated with possession of a substance use disorder, antisocial personality disorder and violent charges while incarcerated; however, these factors were not related to release decisions. MI was found to have neither a direct nor an indirect effect on release decisions. While results indicate that release decisions appear, to some extent, to be evidence-based, they also suggest considerable discretion is being implemented by parole board members in release decisions above and beyond consideration of criminal risk factors.

  14. Activation by histamine of bronchial epithelial cells from nonasthmatic subjects.

    PubMed

    Vignola, A M; Campbell, A M; Chanez, P; Lacoste, P; Michel, F B; Godard, P; Bousquet, J

    1993-10-01

    Histamine is a major mediator of the mast cells that are present between epithelial cells in asthma. In asthma, there is an increased expression of ICAM-1 and HLA-DR and an increased spontaneous release of fibronectin. The effect of histamine was tested on bronchial epithelial cells obtained by bronchial brushing from 22 nonasthmatic subjects. The activation of epithelial cells was assessed by immunocytochemical analysis of the expression of membrane markers (ICAM-1 and HLA-DR) using the alkaline phosphatase-anti-alkaline phosphatase method and the release of fibronectin (enzyme immunoassay). Time-response (three experiments) and dose-response (six experiments) curves showed that the maximal effect was obtained after an incubation time of 24 h and a dose of 1 microM of histamine. For this time course and concentration, there was a highly significant increase in the number of cells expressing ICAM-1 (before histamine: 10 +/- 11%; after histamine: 32 +/- 20%; P < 0.001) and HLA-DR (before histamine: 8 +/- 7%; after histamine: 23 +/- 20%; P < 0.001) and in the release of fibronectin (before histamine: 30 +/- 20 ng/10(5) viable cells; after histamine: 61 +/- 35 ng/10(5) viable cells; P < 0.003). Cycloheximide blocked these effects, suggesting that histamine requires protein synthesis for its action. Pyrilamine (H1-blocker) and ranitidine (H2-blocker) at a concentration of 10 microM decreased the effect of histamine. However, there was no additive effect when both antagonists were added. This study suggests that mast cells present in the airways have a role in the activation of epithelial cells.

  15. Role of Histamine and Its Receptors in Cerebral Ischemia

    PubMed Central

    2012-01-01

    Histamine is recognized as a neurotransmitter or neuromodulator in the brain, and it plays a major role in the pathogenic progression after cerebral ischemia. Extracellular histamine increases gradually after ischemia, and this may come from histaminergic neurons or mast cells. Histamine alleviates neuronal damage and infarct volume, and it promotes recovery of neurological function after ischemia; the H1, H2, and H3 receptors are all involved. Further studies suggest that histamine alleviates excitotoxicity, suppresses the release of glutamate and dopamine, and inhibits inflammation and glial scar formation. Histamine may also affect cerebral blood flow by targeting to vascular smooth muscle cells, and promote neurogenesis. Moreover, endogenous histamine is an essential mediator in the cerebral ischemic tolerance. Due to its multiple actions, affecting neurons, glia, vascular cells, and inflammatory cells, histamine is likely to be an important target in cerebral ischemia. But due to its low penetration of the blood-brain barrier and its wide actions in the periphery, histamine-related agents, like H3 antagonists and carnosine, show potential for cerebral ischemia therapy. However, important questions about the molecular aspects and pathophysiology of histamine and related agents in cerebral ischemia remain to be answered to form a solid scientific basis for therapeutic application. PMID:22860191

  16. Involvement of platelet activating factor, histamine and serotonin in acute lethal shock induced by Candida albicans water-soluble extracellular polysaccharide fraction (CAWS) in mice.

    PubMed

    Nagi-Miura, Noriko; Shingo, Yuko; Kurihara, Kiyoshi; Adachi, Yoshiyuki; Suzuki, Kazuo; Ohno, Naohito

    2007-07-01

    CAWS (Candida albicans water-soluble extracellular polysaccharide fraction) is a water-soluble extracellular mannoprotein-beta-glucan complex obtained from the culture supernatant following the culture of pathogenic Candida albicans in a completely synthetic medium. CAWS administered intraperitoneally induces vasculitis in mice, however, administered intravenously, it causes lethal shock. The acute lethal reaction to CAWS occurs within 1 h of intravenous administration, with the mice demonstrating anaphylactic shock-like symptoms including convulsion, diarrhea, and collapse. In this study, we analyzed the factors involved in this lethal effect. We examined physiologically active substances believed to be involved in anaphylactic shock, and found that the lethal effect of CAWS could be inhibited by blocking histamine, serotonin, and platelet activating factor (PAF) simultaneously, but by blocking only one. This finding strongly suggests that the acute lethal reaction to CAWS is a result of the simultaneous production of several physiologically active substances.

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

    PubMed

    Bugajski, J; Janusz, Z

    1981-04-01

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

  18. Noradrenaline release in the rat vena cava is inhibited by gamma-aminobutyric acid via GABAB receptors but not affected by histamine.

    PubMed Central

    Schneider, D.; Schlicker, E.; Malinowska, B.; Molderings, G.

    1991-01-01

    1. Segments of the rat vena cava preincubated with [3H]-noradrenaline were superfused with [3H]-noradrenaline-free solution containing desipramine and corticosterone and the effects of gamma-aminobutyric acid (GABA) receptor ligands and of histamine on tritium overflow evoked by transmural electrical stimulation were studied. 2. GABA inhibited, and histamine failed to affect, the electrically (0.66 Hz) evoked tritium overflow both in the absence and presence of rauwolscine (which was present in the superfusion medium in the subsequent experiments). The effect of GABA was less pronounced at a stimulation frequency of 2 Hz. 3. The inhibitory effect of GABA (pIC35 5.83) on the electrically (0.66 Hz) evoked overflow was mimicked by the GABAB receptor agonist, R-(-)-baclofen (6.07) and less potently by S-(+)-baclofen (3.30) and the GABAA receptor agonist, muscimol (3.70). The concentration-response curve of GABA was shifted to the right by the GABAB receptor antagonist, CGP 35348 (P-(3-aminopropyl)-P- diethoxymethyl-phosphinic acid; apparent pA2 4.76), but not affected by the GABAA receptor antagonist, (-)-bicuculline methiodide 100 mumol l-1. Given alone, (-)-bicuculline methiodide slightly increased, and CGP 35348 did not affect, the evoked overflow. 4. The effect of GABA in veins from rats treated for 14 days with RS-baclofen (10 mg kg-1, i.p. once daily) did not differ from that in veins from rats which received the vehicle instead. The effect of GABA also did not differ in veins from rats treated once either with RS-baclofen or with its vehicle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1665738

  19. Is the analysis of histamine and/or interleukin-4 release after isocyanate challenge useful in the identification of patients with IgE-mediated isocyanate asthma?

    PubMed

    Blindow, Silke; Preisser, Alexandra M; Baur, Xaver; Budnik, Lygia T

    2015-07-01

    Isocyanates are a well-known and frequent cause of occupational asthma. The implementation of specific inhalation challenges (SICs) is the gold standard in asthma diagnosis supporting occupational case history, lung function testing, specific skin prick tests and the detection of specific IgE. However, the diagnosis is not always definitive. An interesting new approach, analyses of individual genetic susceptibilities, requires discrimination between a positive SIC reaction arising from IgE-mediated immune responses and one from other pathophysiological mechanisms. Hence, additional refinement tools would be helpful in defining sub-classes of occupational asthma and diagnosis. We used total IgE levels, specific IgE and SIC results for sub-classification of 27 symptomatic isocyanate workers studied. Some mutations in glutathione S-transferases (GSTs) are suspected either to enhance or to decrease the individual risk in the development of isocyanate asthma. Our patient groups were assessed for the point mutations GSTP1*I105V and GSTP1*A114V as well as deletions (null mutations) of GSTM1 and GSTT1. There seems to be a higher risk in developing IgE-mediated reactions when GSTM1 is deleted, while GSTT1 deletions were found more frequently in the SIC positive group. Blood samples taken before SIC, 30-60 min and 24h after SIC, were analyzed for histamine and IL-4, classical markers for the IgE-mediated antigen-specific activation of basophils or mast cells. We suggest that the utility of histamine measurements might provide an additional useful marker reflecting isocyanate-induced cellular reactions (although the sampling times require optimization). The promising measurement of IL-4 is not feasible at present due to the lack of a reliable, validated assay.

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

    PubMed

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

    1988-12-01

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

  1. Histamine and motivation

    PubMed Central

    Torrealba, Fernando; Riveros, Maria E.; Contreras, Marco; Valdes, Jose L.

    2012-01-01

    Brain histamine may affect a variety of different behavioral and physiological functions; however, its role in promoting wakefulness has overshadowed its other important functions. Here, we review evidence indicating that brain histamine plays a central role in motivation and emphasize its differential involvement in the appetitive and consummatory phases of motivated behaviors. We discuss the inputs that control histaminergic neurons of the tuberomamillary nucleus (TMN) of the hypothalamus, which determine the distinct role of these neurons in appetitive behavior, sleep/wake cycles, and food anticipatory responses. Moreover, we review evidence supporting the dysfunction of histaminergic neurons and the cortical input of histamine in regulating specific forms of decreased motivation (apathy). In addition, we discuss the relationship between the histamine system and drug addiction in the context of motivation. PMID:22783171

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

    PubMed

    Reese, Imke

    2016-06-01

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

  3. A novel double-isotope technique for the enzymatic assay of plasma histamine: application to estimation of mast cell activation assessed by antigen challenge in asthmatics.

    PubMed

    Brown, M J; Ind, P W; Causon, R; Lee, T H

    1982-01-01

    The concentration of plasma histamine may provide an index of mast cell activation (degranulation) and can be measured by a sensitive radioenzymatic assay based on its specific conversion to (3H)-methylhistamine in the presence of histamine-N-methyltransferase and (3H)-S-adenosyl-L-methionine. In this assay, the separation of excess (3H)-S-adenosyl-L-methionine from (3H)-methylhistamine requires several steps, for which a correction factors is necessary to maintain precision. In the present modification, duplicate 50-microliters aliquots of each plasma sample were incubated with histamine-N-methyltransferase and (3H)-S-adenosyl-L-methionine. A further aliquot, with an added standard of 200 ng/ml histamine, was incubated with histamine-N-methyl-transferase and (14C)-S-adenosyl-L-methionine. This standard was converted to (14C)-methylhistamine, and its recovery at the end of the assay corrected both for varying efficiency of methylation among plasma samples and for losses during the subsequent extraction and separation stages. The sensitivity of the assay was 25 pg/ml. The intra-assay and interassay coefficients of variation were 7.2% and 11.6%, respectively. In five asthmatics, antigen challenge caused a 28% fall in FEV1, and this was associated with a twofold to threefold rise in plasma histamine concentration. This assay may thus prove a useful method for assessing the role of mast cell release of mediators in vivo.

  4. A novel double-isotope technique for the enzymatic assay of plasma histamine: application to estimation of mast cell activation assessed by antigen challenge in asthmatics

    SciTech Connect

    Brown, M.J.; Ind, P.W.; Causon, R.; Lee, T.H.

    1982-01-01

    The concentration of plasma histamine may provide an index of mast cell activation (degranulation) and can be measured by a sensitive radioenzymatic assay based on its specific conversion to (/sup 3/H)-methylhistamine in the presence of histamine-N-methyltransferase and (/sup 3/H)-S-adenosyl-L-methionine. In this assay, the separation of excess (/sup 3/H)-S-adenosyl-L-methionine from (/sup 3/H)-methylhistamine requires several steps, for which a correction factors is necessary to maintain precision. In the present modification, duplicate 50-microliters aliquots of each plasma sample were incubated with histamine-N-methyltransferase and (/sup 3/H)-S-adenosyl-L-methionine. A further aliquot, with an added standard of 200 ng/ml histamine, was incubated with histamine-N-methyl-transferase and (/sup 14/C)-S-adenosyl-L-methionine. This standard was converted to (/sup 14/C)-methylhistamine, and its recovery at the end of the assay corrected both for varying efficiency of methylation among plasma samples and for losses during the subsequent extraction and separation stages. The sensitivity of the assay was 25 pg/ml. The intra-assay and interassay coefficients of variation were 7.2% and 11.6%, respectively. In five asthmatics, antigen challenge caused a 28% fall in FEV1, and this was associated with a twofold to threefold rise in plasma histamine concentration. This assay may thus prove a useful method for assessing the role of mast cell release of mediators in vivo.

  5. New kid on the block: does histamine get along with inflammation in amyotrophic lateral sclerosis?

    PubMed

    Volonté, Cinzia; Parisi, Chiara; Apolloni, Savina

    2015-01-01

    Results from amyotrophic lateral sclerosis (ALS) patients and pre-clinical studies strongly suggest that systemic and CNS-intrinsic immune activation plays a central role in ALS pathogenesis. Microglial cells are emerging in this context as master regulators with a bi-functional role in the progression of the pathological response. They foster a pro-inflammatory setting through the production of cytotoxic cytokines and chemokines (M1 phenotype), after an aborted effort to sustain an anti-inflammatory environment for motor neurons through the release of beneficial cytokines and growth factors (M2 phenotype). In this review, we gather information meant to propose that histamine and ATP, which are released from mast cells, microglia and damaged neurons at sites of injury where they function as transmitters, have to be considered as new players in the ALS neuroinflammatory arena. After all, abnormal histamine and ATP signalling in the brain are already documented in neurodegenerative/neuroinflammatory conditions such as multiple sclerosis, Alzheimer and Parkinson's disease and, at present, histamine- as well as ATP-related compounds are in clinical trial for these same pathologies. Concerning ALS, while emerging data are now available about purinergic mechanisms, the involvement of histamine is basically unexplored. The circumstantial evidence that we present here thus constitutes a solid background for formulating novel hypotheses, stimulating a scientific debate and, most of all, inspiring future research. We deem that a new potential role of histamine in the setting of ALS neuroinflammation might find a fertile ground where to thrive. ALS is still a disease without a cure: why not to play with a new kid on the block?

  6. Measurement of urinary histamine: comparison of fluorometric and radioisotopic-enzymatic assay procedures

    SciTech Connect

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

    1982-02-01

    Assessment of urinary histamine may prove useful in determining the role of histamine in human health and disease. Urinary histamine may be accurately estimated by a modified fluorometric assay employing diamine oxidase (DAO) digestion and cation-exchange chromatography. However, the radioisotopic-enzymatic assay is less expensive, easier to perform, and possibly more sensitive. Therefore the two procedures were compared. The radioenzyme assay was found to be affected by factors in urine (possibly salt concentrations) requiring extraction of histamine from urine by butanol-heptane. Moreover, it was found to be necessary to compare DAO-digested samples with undigested samples to accurately estimate histamine levels and to run the standard curve of histamine in DAO-digested urine. Even with these modifications, the radioenzyme assay was not as accurate as the fluorometric assay for urine samples having histamine values about 60 ng/ml. Therefore we recommend utilization of the modified fluorometric assay for the measurement of urinary histamine levels.

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

    PubMed

    Vidrio, H; Priola, D V

    1990-03-01

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

  8. Histamine and H1-histamine receptors faster venous circulation

    PubMed Central

    Galajda, Zoltan; Balla, Jozsef; Szentmiklosi, A Jozsef; Biro, Tamas; Czifra, Gabriella; Dobrosi, Nora; Cseppento, Agnes; Patonay, Lajos; Roszer, Tamas; Balla, Gyorgy; Popescu, Laurenciu M; Lekli, Istvan; Tosaki, Arpad

    2011-01-01

    Abstract The study has analysed the action of histamine in the rabbit venous system and evaluated its potential role in contraction during increased venous pressure. We have found that a great variety exists in histamine sensitivity and H1-histamine receptor expression in various types of rabbit veins. Veins of the extremities (saphenous vein, femoral vein, axillary vein) and abdomen (common iliac vein, inferior vena cava) responded to histamine by a prominent, concentration-dependent force generation, whereas great thoracic veins (subclavian vein, superior vena cavas, intrathoracic part of inferior vena cava) and a pelvic vein (external iliac vein) exhibited slight sensitivity to exogenous histamine. The lack of reactivity to histamine was not due to increased activity of nitric oxide synthase (NOS) or heme oxygenase-1. H1-histamine receptor expression of veins correlated well with the histamine-induced contractions. Voltage-dependent calcium channels mediated mainly the histamine-induced force generation of saphenous vein, whereas it did not act in the inferior vena cava. In contrast, the receptor-operated channels were not involved in this response in either vein. Tyrosine phosphorylation occurred markedly in response to histamine in the saphenous vein, but not in the inferior vena cava. Histamine induced a prominent ρ kinase activation in both vessels. Protein kinase C and mitogen-activated protein kinase (MAPK) were not implicated in the histamine-induced intracellular calcium sensitization. Importantly, transient clamping of the femoral vein in animals caused a short-term constriction, which was inhibited by H1-histamine receptor antagonist in vivo. Furthermore, a significantly greater histamine immunopositivity was detected in veins after stretching compared to the resting state. We conclude that histamine receptor density adapts to the actual requirements of the circulation, and histamine liberated by the venous wall during increased venous pressure

  9. Effects of histamine on light responses of amacrine cells in tiger salamander retina.

    PubMed

    Yu, Yongchun; Satoh, Hiromasa; Vila, Alejandro; Wu, Samuel M; Marshak, David W

    2011-04-01

    Using immunofluorescence, we showed that histamine receptor 1 is expressed by horizontal cell axons and a subset of amacrine cells in the tiger salamander retina. The effects of histamine on light responses of amacrine cells were studied in slice preparations. Histamine modulated the light responses of many salamander amacrine cells, depending upon the morphological type. The most pronounced effects of histamine were decreases in the light responses of broadly stratified amacrine cells, particularly those having medium-sized dendritic field diameters. To determine whether the effects of histamine were direct, Co(++) was substituted for Ca(++) in the extracellular medium to block synaptic transmission. Histamine still affected broadly stratified amacrine cells, but not narrowly stratified amacrine cells under these conditions. Taken together, these findings suggest that inhibitory interactions between strata of the IPL and within the classical receptive fields of the ganglion cells would be particularly sensitive to histamine released from retinopetal axons.

  10. Effects of Histamine on Light Responses of Amacrine Cells in Tiger Salamander Retina

    PubMed Central

    Yu, Yongchun; Satoh, Hiromasa; Vila, Alejandro; Wu, Samuel M.; Marshak, David W.

    2011-01-01

    Using immunofluorescence, we showed that histamine receptor 1 is expressed by horizontal cell axons and a subset of amacrine cells in the tiger salamander retina. The effects of histamine on light responses of amacrine cells were studied in slice preparations. Histamine modulated the light responses of many salamander amacrine cells, depending upon the morphological type. The most pronounced effects of histamine were decreases in the light responses of broadly stratified amacrine cells, particularly those having medium-sized dendritic field diameters. To determine whether the effects of histamine were direct, Co++ was substituted for Ca++ in the extracellular medium to block synaptic transmission. Histamine still affected broadly stratified amacrine cells, but not narrowly stratified amacrine cells under these conditions. Taken together, these findings suggest that inhibitory interactions between strata of the IPL and within the classical receptive fields of the ganglion cells would be particularly sensitive to histamine released from retinopetal axons. PMID:20878231

  11. The release of a non-prostanoid inhibitory factor from rabbit bronchus detected by co-axial bioassay.

    PubMed

    Spina, D; Page, C P

    1991-04-01

    1. Methacholine relaxed phenylephrine-contracted aorta of the rat with the endothelium intact. This effect was inhibited by haemoglobin, methylene blue, gossypol, phenidone and L-NG-nitroarginine methyl ester (L-NAME). Rat aorta denuded of endothelium failed to relax in response to methacholine, histamine and the peptidoleukotrienes C4, D4 and E4. 2. Methacholine and histamine but not leukotrienes C4, D4 and E4 relaxed phenylephrine-contracted rat aorta without endothelium when surrounded by rabbit epithelium-intact bronchus. The muscarinic antagonist atropine antagonized the methacholine-induced relaxation. 3. Removal of the epithelium either mechanically or chemically, abolished methacholine-induced relaxation of rat aorta in the co-axial bioassay. These data indicate that the epithelium is responsible for the observed relaxant effect to methacholine and histamine. 4. The cyclo-oxygenase inhibitor, indomethacin, the phospholipase A2 inhibitor, mepacrine and the lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA), failed to inhibit methacholine-induced relaxation of rat aorta in the co-axial bioassay. This indicates that the epithelium-derived inhibitory factor (EpDIF) is not a product of the cyclo-oxygenase or lipoxygenase pathway or a product derived from activation of phospholipase A2. 5. Haemoglobin, methylene blue, phenidone, gossypol and L-NAME failed to inhibit the relaxation of rat aorta in the co-axial bioassay. These results demonstrate that EpDIF detected in the co-axial bioassay is not endothelium-derived relaxing factor (EDRF) or nitric oxide. Similarly, catalase was without effect. 6. EpDIF is unlikely to be a peptide since papain and alpha-chymotrypsin failed to alter the methacholine-induced relaxation of rat aorta in the co-axial bioassay. Furthermore, thiorphan, captopril and aprotinin were also without effect, suggesting that EpDIF is not a substrate for airway peptidases. 7. The results presented in this paper demonstrate the release of a

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

    PubMed

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

    2015-01-01

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

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

    PubMed

    de Almeida, M A; Izquierdo, I

    1988-01-01

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

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

    PubMed

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

    2015-06-07

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

  15. Factors affecting water quality in the releases from hydropower reservoirs

    SciTech Connect

    Ruane, R.J.; Hauser, G.E. )

    1990-01-01

    Typical water quality concerns with releases from hydropower reservoirs include low dissolved oxygen, inappropriate temperature for downstream uses, supersaturation of total dissolved gases, and water quality constituents associated with low dissolved oxygen. Except for supersaturation of total dissolved gases, which is usually caused by by-passing turbines and spilling water, all of these concerns are related to the limnology of the upstream reservoir. Various limnological factors affect water quality, particularly dissolved oxygen (DO) in turbine releases. This paper describes three groups of reservoirs, thermal stratification characteristics for each group, DO effects for each group, the main factors that affect DO in TVA turbine releases, and other water quality constituents that are related to low DO.

  16. Kinetics of Stop Codon Recognition by Release Factor 1

    PubMed Central

    Hetrick, Byron; Lee, Kristin; Joseph, Simpson

    2009-01-01

    Recognition of stop codons by class I release factors is a fundamental step in the termination phase of protein synthesis. Since premature termination is costly to the cell, release factors have to efficiently discriminate between stop and sense codons. In order to understand the mechanism of discrimination between stop and sense codons, we developed a new, pre-steady state kinetic assay to monitor the interaction of RF1 with the ribosome. Our results show that RF1 associates with similar association rate constants to ribosomes programmed with a stop or sense codons. However, dissociation of RF1 from sense codons is as much as three orders of magnitude faster than from stop codons. Interestingly, the affinity of RF1 for ribosomes programmed with different sense codons does not correlate with the defects in peptide release. Thus, discrimination against sense codons is achieved, both, by increasing the dissociation rates and by decreasing the rate of peptide release. These results suggest that sense codons inhibit conformational changes necessary for RF1 to stably bind to the ribosome and catalyze peptide release. PMID:19874047

  17. Therapeutic approach of histamine H3 receptors in obesity.

    PubMed

    Masaki, Takayuki; Yoshimatsu, Hironobu

    2007-11-01

    Obesity is considered one of the risk factors for metabolic disorders. There is increasing evidence that obesity is under control of several cytokines and hormone in the brain. Brain histamine and H3 receptors are important factors for regulating obesity. The results of physiological and pharmacological studies revealed that brain histamine and H3 receptors are involved in the regulation of obesity. In this review, we describe the implication and patent for developing H3 receptor antagonists and their therapeutic potential of obesity.

  18. Histamine and histamine receptor antagonists in cancer biology.

    PubMed

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

    2010-07-01

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

  19. Release characteristics of encapsulated formulations incorporating plant growth factors.

    PubMed

    Wybraniec, Slawomir; Schwartz, Liliana; Wiesman, Zeev; Markus, Arie; Wolf, David

    2002-05-01

    The release characteristics of encapsulated formulations containing a combination of plant growth factors (PGF)--plant hormones (IBA, paclobutrazol), nutrients (fertilizers, microelements), and fungicide (prochloraz)--were studied. The formulations were prepared by encapsulating the active ingredients in a polyethylene matrix and, in some cases, subsequently coating the product with polyurethane. Dissolution experiments were carried out with both coated and non-coated formulations to determine the sustained release patterns of the active ingredients. The PGF controlled-release systems obtained have been shown to promote development of root systems, vegetative growth, and reproductive development in cuttings, potted plants, or garden plants of various plant species. These beneficial effects are attributable to the lasting and balanced PGF availability provided by these systems.

  20. [Presynaptic histamine H3-receptors exist on cardiac sympathetic terminals of guinea pig].

    PubMed

    Luo, X X

    1995-07-01

    This is the first time to report the existence of new presynaptic inhibitory autoreceptors--histamine H3-receptors in guinea pig myocardium. We found that (R)-alpha-methylhistamine (alpha-MeHA), a selective histamine H3-receptor agonist, attenuates the sympathetic inotropic response of isolated guinea pig atria elicited by electrical field stimulation. This inhibition was associated with a marked reduction in endogenous norepinephrine release. The above phenomenon was antagonised by selective histamine H3-receptor antagonists, and inhibited by pretreatment with N ethylmeleimide. The cardiac sympathetic response could be attenuated or facilitated by increase or decrease of endogenous histamine. Our findings indicate that the endogenous histamine might be involved in the modulation of cardiac sympathetic neurotransmission by interacting with histamine H3-receptors and the receptors are probably coupled to a G(o)/Gi protein.

  1. Histidine 197 in Release Factor 1 is Essential for A Site Binding and Peptide Release

    PubMed Central

    Field, Andrew; Hetrick, Byron; Mathew, Merrill; Joseph, Simpson

    2010-01-01

    Class I peptide release factors 1 and 2 (RF1 and RF2) recognize the stop codons in the ribosomal decoding center and catalyze peptidyl-tRNA hydrolysis. High-fidelity stop codon recognition by these release factors is essential for accurate peptide synthesis and ribosome recycling. X-ray crystal structures of RF1 and RF2 bound to the ribosome have identified residues in the mRNA-protein interface that appear critical for stop codon recognition. Especially interesting is a conserved histidine in all bacterial class I release factors that forms a stacking interaction with the second base of the stop codon. Here we analyzed the functional significance of this conserved histidine (197 in E. coli) of RF1 by point mutagenesis to alanine. Equilibrium binding studies and transient-state kinetic analysis have shown that the histidine is essential for binding with high affinity to the ribosome. Furthermore, analysis of the binding data indicates a conformational change within the RF1•ribosome complex that results in a more tightly bound state. The rate of peptidyl-tRNA hydrolysis was also reduced significantly, more than the binding data would suggest, implying a defect in the orientation of the GGQ domain without the histidine residue. PMID:20873815

  2. Sulodexide induces hepatocyte growth factor release in humans.

    PubMed

    Borawski, Jacek; Dubowski, Miroslaw; Pawlak, Krystyna; Mysliwiec, Michal

    2007-03-08

    Heparin influences numerous pleiotropic growth factors, including hepatocyte growth factor (HGF), partially by their release from endothelial and extracellular matrix stores. The effects of sulodexide, a heparin-like glycosaminoglycan medication of growing importance in medicine, on HGF liberation are not known. We performed a 2-week open-label sulodexide trial in healthy male volunteers. The drug was initially administered intravenously (i.v.) in a single dose of 1200 Lipoprotein Lipase Releasing Units (LRU), then -- orally for 12 days (500 LRU twice a day), and -- again by i.v. route (1200 LRU) on day 14. Intravenous sulodexide injections were repeatedly found to induce marked and reproducible increases in immunoreactive plasma HGF levels (more than 3500% vs baseline after 10 min, and more than 1200% after 120 min), and remained unchanged when measured 120 min following oral sulodexide administration. The percentage increments in plasma HGF evoked by i.v. sulodexide at both time points and on both days inversely correlated with baseline levels of the growth factor. On day 14, the HGF levels after 120 min and their percentage increase vs baseline were strongly and directly dependent on i.v. sulodexide dose per kg of body weight. This study shows that sulodexide has a novel, remarkable and plausibly biologically important stimulating effect on the release of pleiotropic hepatocyte growth factor in humans.

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

    PubMed

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

    2004-01-19

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

  4. Histamine regulates memory consolidation.

    PubMed

    Passani, Maria Beatrice; Benetti, Fernando; Blandina, Patrizio; Furini, Cristiane R G; de Carvalho Myskiw, Jociane; Izquierdo, Ivan

    2017-08-23

    Recent findings have reasserted the role of histamine in the regulation of memory consolidation first proposed in 1986 in an inhibitory avoidance task in rats. They indicate that histamine is indeed a major regulator of memory consolidation in various tasks, through H2 receptors in the dorsal hippocampus and through H3 receptors in the basolateral amygdala, depending on the task. In the object recognition task, the memory enhancing effect is mediated by the three receptors (H1, H2, H3) in the dorsal hippocampus. In social recognition, the consolidation effect is mediated by H2 receptors in both amygdala and dorsal hippocampus. Data have suggested, in addition, influences on retrieval; this has been best studied in the dorsal hippocampus in step-down inhibitory avoidance task. Depending on the recent history of the conditioned stimulus (i.e., whether it has been recently reinforced or not), histamine acts on hippocampal H1 receptors, facilitating retrieval, or on H2 receptors, inhibiting it. Copyright © 2017. Published by Elsevier Inc.

  5. Interactions of release factor RF3 with the translation machinery.

    PubMed

    O'Connor, Michael

    2015-08-01

    The bacterial release factor RF3 is a GTPase that has been implicated in multiple, incompletely understood steps of protein synthesis. This study explores the genetic interaction of RF3 with other components of the translation machinery. RF3 contributes to translation termination by recycling the class I release factors RF1 and RF2 off post-termination ribosomes. RF3 has also been implicated in dissociation of peptidyl-tRNAs from elongating ribosomes and in a post-peptidyltransferase quality control (post-PT QC) mechanism that selectively terminates ribosomes carrying erroneous peptides. A majority of the in vivo studies on RF3 have been carried out in K-12 strains of Escherichia coli which carry a partially defective RF2 protein with an Ala to Thr substitution at position 246. Here, the contribution of the K-12 specific RF2 variant to RF3 activities has been investigated. Strain reconstruction experiments in both E. coli and Salmonella enterica demonstrate that defects in termination and post-PT QC that are associated with RF3 loss, as well as phenotypes uncovered by phenotypic profiling, are all substantially ameliorated when the incompletely active K-12-specific RF2 protein is replaced by a fully active Ala246 RF2. These results indicate that RF3 loss is well tolerated in bacteria with fully active class I release factors, but that many of the previously reported phenotypes for RF3 deletion strains have been compromised by the presence of a partially defective RF2.

  6. Polyelectrolyte complexes stabilize and controllably release vascular endothelial growth factor.

    PubMed

    Huang, Min; Vitharana, Samadhi N; Peek, Laura J; Coop, Tina; Berkland, Cory

    2007-05-01

    Angiogenesis has long been a desired therapeutic approach to improve clinical outcomes of conditions typified by ischemia. Vascular endothelial growth factor (VEGF) has demonstrated the ability to generate new blood vessels in vivo, but trials using intravenous delivery have not yet produced clinical success. Localized, sustained delivery of VEGF has been proven necessary to generate blood vessels as demonstrated by implantable, controlled release devices. Ultimately, nanoparticles delivered by intravenous injection may be designed to accumulate in target tissues and sustain the local VEGF concentration; however, injectable nanosuspensions that control the release of stabilized VEGF must first be developed. In this study, we utilize the heparin binding domain of VEGF to bind the polyanion dextran sulfate, resulting in an enhanced thermal stability of VEGF. Coacervation of the VEGF-bound dextran sulfate with selected polycations (chitosan, polyethylenimine, or poly-L-lysine) produced nanoparticles approximately 250 nm in diameter with high VEGF encapsulation efficiency (50-85%). Release of VEGF from these formulations persisted for >10 days and maintained high VEGF activity as determined by ELISA and a mitogenic bioassay. Chitosan-dextran sulfate complexes were preferred because of their biodegradability, desirable particle size ( approximately 250 nm), entrapment efficiency ( approximately 85%), controlled release (near linear for 10 days), and mitogenic activity.

  7. Distribution and release of epidermal growth factor in man.

    PubMed Central

    Konturek, J W; Bielanski, W; Konturek, S J; Bogdal, J; Oleksy, J

    1989-01-01

    Epidermal growth factor (EGF) is localised in man to salivary and Brunner's glands. It is present in large concentrations in saliva and duodenal contents but the mechanisms of its release have been little studied. This study carried out on four groups of healthy subjects was designed to determine the distribution and the release of immunoreactive EGF (IR-EGF) in salivary, gastric, duodenal, and pancreatic secretions. Under basal conditions, the concentrations of IR-EGF in salivary, gastric, duodenal and pancreatic secretions were; 2.7 (0.4), 0.42 (0.12), 21 (5) and 8.5 (1.2) ng/ml, respectively. Chewing of Parafilm* significantly increased salivary but not gastric or duodenal EGF output while atropinisation led to the reduction in basal salivary and duodenal EGF output without affecting the increment in EGF release induced by chewing. Cigarette smoking caused a marked reduction in basal salivary and duodenal EGF output. Infusion of pentagastrin increased salivary and duodenal EGF output and this was blocked by the addition of somatostatin. Injection of secretin lead to an increase in pancreatic output of EGF. We conclude that in man the major sources of EGF are salivary glands, duodenum, and pancreas and that the release of EGF remains under neurohormonal control. PMID:2806986

  8. Gelatin Methacrylate Microspheres for Growth Factor Controlled Release

    PubMed Central

    Nguyen, Anh H.; McKinney, Jay; Miller, Tobias; Bongiorno, Tom; McDevitt, Todd C.

    2014-01-01

    Gelatin has been commonly used as a delivery vehicle for various biomolecules for tissue engineering and regenerative medicine applications due to its simple fabrication methods, inherent electrostatic binding properties, and proteolytic degradability. Compared to traditional chemical cross-linking methods, such as the use of glutaraldehyde (GA), methacrylate modification of gelatin offers an alternative method to better control the extent of hydrogel cross-linking. Here we examined the physical properties and growth factor delivery of gelatin methacrylate (GMA) microparticles formulated with a wide range of different cross-linking densities (15–90%). Less methacrylated MPs had decreased elastic moduli and larger mesh sizes compared to GA MPs, with increasing methacrylation correlating to greater moduli and smaller mesh sizes. As expected, an inverse correlation between microparticle cross-linking density and degradation was observed, with the lowest cross-linked GMA MPs degrading at the fastest rate, comparable to GA MPs. Interestingly, GMA MPs at lower cross-linking densities could be loaded with up to a 10-fold higher relative amount of growth factor over conventional GA cross-linked MPs, despite an order of magnitude greater gelatin content of GA MPs. Moreover, a reduced GMA cross-linking density resulted in more complete release of bone morphogenic protein 4 (BMP4) and basic fibroblast growth factor (bFGF) and accelerated release rate with collagenase treatment. These studies demonstrate that GMA MPs provide a more flexible platform for growth factor delivery by enhancing the relative binding capacity and permitting proteolytic degradation tunability, thereby offering a more potent controlled release system for growth factor delivery. PMID:25463489

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

    PubMed

    Bernsand, M; Ericsson, P; Bjorkqvist, M; Zhao, C-M; Hakanson, R; Norlen, P

    2003-10-01

    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 between the histamine-mobilizing effects of gastrin, and of endothelin and adrenaline. Endothelin, adrenaline or gastrin were administered by submucosal microinfusion. Gastric histamine mobilization was monitored by microdialysis. Local pretreatment with the H1-receptor antagonist mepyramine and the H2-receptor antagonist ranitidine did not prevent endothelin- or adrenaline-induced mucosal damage. Submucosal microinfusion of histamine did not cause damage. Acid blockade by ranitidine or omeprazole prevented the damage, suggesting that acid back diffusion contributes. Gastrin raised histidine decarboxylase (HDC) activity close to the probe, without affecting the histamine concentration. Endothelin and adrenaline lowered histamine by 50-70%, without activating HDC. Histamine mobilization declined upon repeated administration. Endothelin reduced the number of histamine-immunoreactive ECL cells locally, and reduced the number of secretory vesicles. Thus, unlike gastrin, endothelin (and adrenaline) is capable of exhausting ECL-cell histamine. Microinfusion of alpha-fluoromethylhistidine (known to deplete ECL cells but not mast cells of histamine) reduced the histamine-mobilizing effect of endothelin by 80%, while 1-week pretreatment with omeprazole enhanced it, supporting the involvement of ECL cells. Somatostatin or the prostanoid misoprostol inhibited gastrin-, but not endothelin-stimulated histamine release, suggesting that endothelin and gastrin mobilize histamine via

  10. Role of Corticotropin-releasing Factor in Gastrointestinal Permeability

    PubMed Central

    Rodiño-Janeiro, Bruno K; Alonso-Cotoner, Carmen; Pigrau, Marc; Lobo, Beatriz; Vicario, María; Santos, Javier

    2015-01-01

    The interface between the intestinal lumen and the mucosa is the location where the majority of ingested immunogenic particles face the scrutiny of the vast gastrointestinal immune system. Upon regular physiological conditions, the intestinal micro-flora and the epithelial barrier are well prepared to process daily a huge amount of food-derived antigens and non-immunogenic particles. Similarly, they are ready to prevent environmental toxins and microbial antigens to penetrate further and interact with the mucosal-associated immune system. These functions promote the development of proper immune responses and oral tolerance and prevent disease and inflammation. Brain-gut axis structures participate in the processing and execution of response signals to external and internal stimuli. The brain-gut axis integrates local and distant regulatory networks and super-systems that serve key housekeeping physiological functions including the balanced functioning of the intestinal barrier. Disturbance of the brain-gut axis may induce intestinal barrier dysfunction, increasing the risk of uncontrolled immunological reactions, which may indeed trigger transient mucosal inflammation and gut disease. There is a large body of evidence indicating that stress, through the brain-gut axis, may cause intestinal barrier dysfunction, mainly via the systemic and peripheral release of corticotropin-releasing factor. In this review, we describe the role of stress and corticotropin-releasing factor in the regulation of gastrointestinal permeability, and discuss the link to both health and pathological conditions. PMID:25537677

  11. IgE enhances Fc epsilon receptor I expression and IgE-dependent release of histamine and lipid mediators from human umbilical cord blood-derived mast cells: synergistic effect of IL-4 and IgE on human mast cell Fc epsilon receptor I expression and mediator release.

    PubMed

    Yamaguchi, M; Sayama, K; Yano, K; Lantz, C S; Noben-Trauth, N; Ra, C; Costa, J J; Galli, S J

    1999-05-01

    We investigated the effects of IgE versus IL-4 on Fc epsilon RI surface expression in differentiated human mast cells derived in vitro from umbilical cord blood mononuclear cells. We found that IgE (at 5 micrograms/ml) much more strikingly enhanced surface expression of Fc epsilon RI than did IL-4 (at 0.1-100 ng/ml); similar results were also obtained with differentiated mouse mast cells. However, IL-4 acted synergistically with IgE to enhance Fc epsilon RI expression in these umbilical cord blood-derived human mast cells, as well as in mouse peritoneal mast cells derived from IL-4-/- or IL-4+/+ mice. We also found that: 1) IgE-dependent enhancement of Fc epsilon RI expression was associated with a significantly enhanced ability of these human mast cells to secrete histamine, PGD2, and leukotriene C4 upon subsequent passive sensitization with IgE and challenge with anti-IgE; 2) preincubation with IL-4 enhanced IgE-dependent mediator secretion in these cells even in the absence of significant effects on Fc epsilon RI surface expression; 3) when used together with IgE, IL-4 enhanced IgE-dependent mediator secretion in human mast cells to levels greater than those observed in cells that had been preincubated with IgE alone; and 4) batches of human mast cells generated in vitro from umbilical cord blood cells derived from different donors exhibited differences in the magnitude and pattern of histamine and lipid mediator release in response to anti-IgE challenge, both under baseline conditions and after preincubation with IgE and/or IL-4.

  12. Drosophila factor 2, an RNA polymerase II transcript release factor, has DNA-dependent ATPase activity.

    PubMed

    Xie, Z; Price, D

    1997-12-12

    Drosophila factor 2 has been identified as a component of negative transcription elongation factor (N-TEF) that causes the release of RNA polymerase II transcripts in an ATP-dependent manner (Xie, Z. and Price D. H. (1996) J. Biol. Chem. 271, 11043-11046). We show here that the transcript release activity of factor 2 requires ATP or dATP and that adenosine 5'-O-(thiotriphosphate) (ATPgammaS), adenosine 5'-(beta,gamma-imino)triphosphate (AMP-PNP), or other NTPs do not support the activity. Factor 2 demonstrated a strong DNA-dependent ATPase activity that correlated with its transcript release activity. At 20 microg/ml DNA, the ATPase activity of factor 2 had an apparent Km(ATP) of 28 microM and an estimated Kcat of 140 min-1. Factor 2 caused the release of nascent transcripts associated with elongation complexes generated by RNA polymerase II on a dC-tailed template. Therefore, no other protein cofactors are required for the transcript release activity of factor 2. Using the dC-tailed template assay, it was found that renaturation of the template was required for factor 2 function.

  13. Histamine H4 receptor mediates eosinophil chemotaxis with cell shape change and adhesion molecule upregulation

    PubMed Central

    Ling, Ping; Ngo, Karen; Nguyen, Steven; Thurmond, Robin L; Edwards, James P; Karlsson, Lars; Fung-Leung, Wai-Ping

    2004-01-01

    During mast cell degranulation, histamine is released in large quantities. Human eosinophils were found to express histamine H4 but not H3 receptors. The possible effects of histamine on eosinophils and the receptor mediating these effects were investigated in our studies. Histamine (0.01–30 μM) induced a rapid and transient cell shape change in human eosinophils, but had no effects on neutrophils. The maximal shape change was at 0.3 μM histamine with EC50 at 19 nM. After 60 min incubation with 1 μM histamine, eosinophils were desensitized and were refractory to shape change response upon histamine restimulation. Histamine (0.01–1 μM) also enhanced the eosinophil shape change induced by other chemokines. Histamine-induced eosinophil shape change was mediated by the H4 receptor. This effect was completely inhibited by H4 receptor-specific antagonist JNJ 7777120 (IC50 0.3 μM) and H3/H4 receptor antagonist thioperamide (IC50 1.4 μM), but not by selective H1, H2 or H3 receptor antagonists. H4 receptor agonists imetit (EC50 25 nM) and clobenpropit (EC50 72 nM) could mimic histamine effect in inducing eosinophil shape change. Histamine (0.01–100 μM) induced upregulation of adhesion molecules CD11b/CD18 (Mac-1) and CD54 (ICAM-1) on eosinophils. This effect was mediated by the H4 receptor and could be blocked by H4 receptor antagonists JNJ 7777120 and thioperamide. Histamine (0.01–10 μM) induced eosinophil chemotaxis with an EC50 of 83 nM. This effect was mediated by the H4 receptor and could be blocked by H4 receptor antagonists JNJ 7777120 (IC50 86 nM) and thioperamide (IC50 519 nM). Histamine (0.5 μM) also enhanced the eosinophil shape change induced by other chemokines. In conclusion, we have demonstrated a new mechanism of eosinophil recruitment driven by mast cells via the release of histamine. Using specific histamine receptor ligands, we have provided a definitive proof that the H4 receptor mediates eosinophil chemotaxis, cell shape change and

  14. Controlled growth factor release from synthetic extracellular matrices

    NASA Astrophysics Data System (ADS)

    Lee, Kuen Yong; Peters, Martin C.; Anderson, Kenneth W.; Mooney, David J.

    2000-12-01

    Polymeric matrices can be used to grow new tissues and organs, and the delivery of growth factors from these matrices is one method to regenerate tissues. A problem with engineering tissues that exist in a mechanically dynamic environment, such as bone, muscle and blood vessels, is that most drug delivery systems have been designed to operate under static conditions. We thought that polymeric matrices, which release growth factors in response to mechanical signals, might provide a new approach to guide tissue formation in mechanically stressed environments. Critical design features for this type of system include the ability to undergo repeated deformation, and a reversible binding of the protein growth factors to polymeric matrices to allow for responses to repeated stimuli. Here we report a model delivery system that can respond to mechanical signalling and upregulate the release of a growth factor to promote blood vessel formation. This approach may find a number of applications, including regeneration and engineering of new tissues and more general drug-delivery applications.

  15. Membrane vesicles released by Avibacterium paragallinarum contain putative virulence factors.

    PubMed

    Ramón Rocha, Marcela O; García-González, Octavio; Pérez-Méndez, Alma; Ibarra-Caballero, Jorge; Pérez-Márquez, Victor M; Vaca, Sergio; Negrete-Abascal, Erasmo

    2006-04-01

    Avibacterium paragallinarum, the causative agent of infectious coryza, releases extracellular membrane vesicles (MVs), containing immunogenic proteins, proteases, putative RTX proteins, haemagglutinin, and nucleic acids, into the medium. MVs ranging 50-300 nm in diameter were observed by electron microscopy. They contained immunogenic proteins in the range of 20-160 kDa, detected using vaccinated or experimentally infected chicken sera raised against Av. paragallinarum, but not in pooled sera from specific pathogen-free chickens. Proteolytic activity was not detected in MVs through zymograms; however, immune recognition of high molecular mass bands was observed by Western blotting using an antiprotease serum against Actinobacillus pleuropneumoniae serotype 1 purified protease, suggesting its presence. MVs agglutinated glutaraldehyde-fixed chicken red blood cells indicating the presence of haemagglutinating antigens. Nucleic acids were also detected inside MVs. Avibacterium paragallinarum releases MVs containing putative virulence factors, which could be important in the pathogenesis of infectious coryza.

  16. Histamine stimulates neurogenesis in the rodent subventricular zone.

    PubMed

    Bernardino, Liliana; Eiriz, Maria Francisca; Santos, Tiago; Xapelli, Sara; Grade, Sofia; Rosa, Alexandra Isabel; Cortes, Luísa; Ferreira, Raquel; Bragança, José; Agasse, Fabienne; Ferreira, Lino; Malva, João O

    2012-04-01

    Neural stem/progenitor cells present in the subventricular zone (SVZ) are a potential source of repairing cells after injury. Therefore, the identification of novel players that modulate neural stem cells differentiation can have a huge impact in stem cell-based therapies. Herein, we describe a unique role of histamine in inducing functional neuronal differentiation from cultured mouse SVZ stem/progenitor cells. This proneurogenic effect depends on histamine 1 receptor activation and involves epigenetic modifications and increased expression of Mash1, Dlx2, and Ngn1 genes. Biocompatible poly (lactic-co-glycolic acid) microparticles, engineered to release histamine in a controlled and prolonged manner, also triggered robust neuronal differentiation in vitro. Preconditioning with histamine-loaded microparticles facilitated neuronal differentiation of SVZ-GFP cells grafted in hippocampal slices and in in vivo rodent brain. We propose that neuronal commitment triggered by histamine per se or released from biomaterial-derived vehicles may represent a new tool for brain repair strategies.

  17. Neuropeptide W stimulates adrenocorticotrophic hormone release via corticotrophin-releasing factor but not via arginine vasopressin.

    PubMed

    Yogo, Kosuke; Oki, Yutaka; Iino, Kazumi; Yamashita, Miho; Shibata, Shoko; Hayashi, Chiga; Sasaki, Shigekazu; Suenaga, Toshiko; Nakahara, Daiichiro; Nakamura, Hirotoshi

    2012-01-01

    Neuropeptide W (NPW) was isolated as an endogenous ligand for NPBWR1, an orphan G protein-coupled receptor localized in the rat brain, including the paraventricular nucleus. It has been reported that central administration of NPW stimulates corticosterone secretion in rats. We hypothesized that NPW activates the hypothalamic-pituitary-adrenal (HPA) axis via corticotrophin-releasing factor (CRF) and/or arginine vasopressin (AVP). NPW at 1 pM to 10 nM did not affect basal or ACTH-induced corticosterone release from dispersed rat adrenocortical cells, or basal and CRF-induced ACTH release from dispersed rat anterior pituitary cells. In conscious and unrestrained male rats, intravenous administration of 2.5 and 25 nmol NPW did not affect plasma ACTH levels. However, intracerebroventricular (icv) administration of 2.5 and 5.0 nmol NPW increased plasma ACTH levels in a dose-dependent manner at 15 min after stimulation (5.0 vs. 2.5 nmol NPW vs. vehicle: 1802 ± 349 vs. 1170 ± 204 vs. 151 ± 28 pg/mL, respectively, mean ± SEM). Pretreatment with astressin, a CRF receptor antagonist, inhibited the increase in plasma ACTH levels induced by icv administration of 2.5 nmol NPW at 15 min (453 ± 176 vs. 1532 ± 343 pg/mL, p<0.05) and at 30 min (564 ± 147 vs. 1214 ± 139 pg/mL, p<0.05) versus pretreatment with vehicle alone. However, pretreatment with [1-(β-mercapto-β, β-cyclopentamethylenepropionic acid), 2-(Ο-methyl)tyrosine]-arg-vasopressin, a V1a/V1b receptor antagonist, did not affect icv NPW-induced ACTH release at any time (p>0.05). In conclusion, we suggest that central NPW activates the HPA axis by activating hypothalamic CRF but not AVP.

  18. Histamine, but not leukotriene C4, is an essential mediator in cold urticaria wheals.

    PubMed

    Nuutinen, Pauliina; Harvima, Ilkka T; Ackermann, Leena

    2007-01-01

    In addition to histamine, leukotriene C4 (LTC4) might also play a role in mediating cold urticaria wheals. To study the significance of LTC4 vs. histamine, 6 patients with cold urticaria were challenged with the ice cube test before and after ingestion of 10 mg cetirizine (antihistamine), 10 mg montelukast (leukotriene antagonist) or a combination of both drugs. Cetirizine diminished the cold-induced wheal by 50+/- 42%. Montelukast had no significant effect, and the combination of both drugs diminished the wheal by 37+/- 33%. Furthermore, a skin microdialysis technique detected the release of histamine in the cold-induced wheal, whereas no LTC4 release was detected. In conclusion, the antihistamine is effective and histamine is released, whereas the leukotriene antagonist is not effective and LTC4 is not released in the cold urticaria wheal.

  19. Histamine H1 receptor cell membrane chromatography online high-performance liquid chromatography with mass spectrometry method reveals houttuyfonate as an activator of the histamine H1 receptor.

    PubMed

    Guo, Ying; Han, Shengli; Cao, Jingjing; Zhang, Tao; He, Langchong

    2014-11-01

    Allergy is an abnormal reaction of the body to an allergen. Histamine is responsible for many of the acute symptoms of allergic diseases. Many of the allergic and inflammatory actions of histamine are mediated by the histamine H1 receptor. In the present study, we established a two-dimensional histamine H1 receptor/cell membrane chromatography with online high-performance liquid chromatography and mass spectrometry method for screening potential histamine-activating components in a traditional Chinese medicine injection. The specification of the method was validated by screening, separating, and identifying a mixed standard solution of diphenhydramine hydrochloride, gefitinib, tamsulosin, and nitrendipine. The Yujin injection, an example of traditional Chinese medicine injection, was screened and potential allergic components acting on the histamine H1 receptor were identified. A Ca(2+) flux assay showed that houttuyfonate and Yujin injection induced calcium release in a dose-dependent manner. This suggests that houttuyfonate is an activator of the histamine H1 receptor. The mechanism of houttuyfonate activation involves phosphorylation of the inositol-1,4,5-trisphosphate receptor. In conclusion, this two-dimensional method can rapidly detect and enrich target components isolated from the Yujin injection. This indicates that individuals with an overexpression of the histamine H1 receptor should be aware of possible allergic reactions when receiving the Yujin injection.

  20. Histamine reverses IL-5-afforded human eosinophil survival by inducing apoptosis: pharmacological evidence for a novel mechanism of action of histamine.

    PubMed

    Hasala, Hannele; Giembycz, Mark A; Janka-Junttila, Mirkka; Moilanen, Eeva; Kankaanranta, Hannu

    2008-01-01

    Eosinophils are essential inflammatory cells in the pathogenesis of asthma and atopic conditions. Histamine, released from mast cells and basophils in response to allergen exposure, is a critical mediator in the allergic response. Histamine exerts its effects via four unequivocally characterized histamine receptors, H(1-4). Several functions of eosinophils have previously been shown to be stimulated by histamine. However, its effects on eosinophil apoptosis are unknown. The aim of the present study was to resolve the effects of histamine on constitutive apoptosis of human eosinophils and on the survival-enhancing action of interleukin (IL)-5. Additional experiments were conducted to elucidate the histamine receptor(s) involved in any response seen and the associated signal transduction cascade. Human isolated peripheral blood eosinophils were cultured in the absence or presence of histamine, IL-5 and receptor antagonists/agonists or mediator inhibitors/analogues. Apoptosis was assessed by measuring the relative DNA content of propidium iodide (PI)-stained cells and the effects were confirmed by morphological analysis with bright field microscopy. Caspase activities were assessed by using commercial Caspase-Glo 3/7, 8 and 9 luminescence assays. Histamine (10-100 microM) partially reversed IL-5-induced human eosinophil survival by enhancing apoptosis as assessed by measuring the relative DNA content of PI-stained cells. This effect was not mediated through any of the known histamine receptors or through non-specific activation of 5-hydroxytryptamine receptors or alpha-adrenoceptors. Moreover, the reversal of IL-5-inhibited eosinophil apoptosis by histamine seemed not to utilize the conventional intracellular second-messenger pathways including cyclic AMP, protein kinase A or phospholipase C. Inhibition of caspase 6 and caspases 1, 10 or 12 reversed the effects of histamine but also inhibited apoptosis in general. In conclusion, the data presented herein indicate that

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

    PubMed

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

    2013-04-24

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

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

    PubMed

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

    2006-09-12

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

  3. Histamine H3 receptor-mediated suppression of inhibitory synaptic transmission in the submucous plexus of guinea-pig small intestine.

    PubMed

    Liu, S; Xia, Y; Hu, H z; Ren, J; Gao, C; Wood, J D

    2000-05-26

    Conventional intracellular microelectrodes and marker injection techniques were used to study the actions of histamine on inhibitory synaptic transmission in the submucous plexus of guinea-pig small intestine. Bath application of histamine (1-300 microM) reversibly suppressed both noradrenergic and non-adrenergic slow inhibitory postsynaptic potentials in a concentration-dependent manner. These effects of histamine were mimicked by the selective histamine H(3) receptor agonist R(-)-alpha-methylhistamine but not the selective histamine H(1) receptor agonist, 6-[2-(4-imidazolyl)ethylamino]-N-(4-trifluoromethylphenyl) heptanecarboxamide (HTMT dimaleate), or the selective histamine H(2) receptor agonist, dimaprit. The histamine H(3) receptor antagonist, thioperamide, blocked the effects of histamine. Histamine H(1) and H(2) receptor antagonists did not change the action of histamine. Hyperpolarizing responses to focal application of norepinephrine or somatostatin by pressure ejection from micropipettes were unaffected by histamine and R(-)-alpha-methylhistamine. The results suggest that histamine acts at presynaptic histamine H(3) receptors on the terminals of sympathetic postganglionic fibers and intrinsic somatostatinergic nerves in the small intestine to suppress the release of the inhibitory neurotransmitters, norepinephrine and somatostatin.

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

    SciTech Connect

    Faraj, B.A.; Gottieb, G.R.; Camp, V.M.; Kutner, M.; Lolies, P.

    1984-01-01

    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 (/sup 3/H-methyl)-S-adenosyl-L-methionine (sp act 15 Ci/mmol) in phosphate buffer, 0.05 mole/l, pH 7.9, at 37/sup 0/C for 60 min. The N-(/sup 3/H-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.

  5. Histamine H3 antagonists as wake-promoting and pro-cognitive agents.

    PubMed

    Stocking, Emily M; Letavic, Michael A

    2008-01-01

    The histamine H3 receptor is a pre-synaptic auto- and hetero-receptor that controls the release of histamine and a variety of other neurotransmitters in the brain. As such, modulation of the histamine H(3) receptor is expected to affect wake via control of the release of histamine and to affect cognition via regulation of several other neurotransmitters including acetylcholine and norepinephrine. Over the last several years numerous pre-clinical studies have shown that histamine H3 antagonists promote wakefulness, improve cognition, and in some cases affect food intake. Based on the interest level generated from these early pharmacology studies, and following the cloning and expression of the human histamine H3 receptor, many pharmaceutical companies began drug discovery programs aimed at the identification of histamine H3 antagonists suitable for human clinical trials. These efforts have led to many new chemotypes, and several promising compounds have recently entered the clinic for a variety of conditions, including ADHD, Narcolepsy, EDS associated with Narcolepsy, Cognitive disorders and Schizophrenia. Recent efforts towards the identification and pharmacological characterization of novel histamine H3 antagonists will be discussed.

  6. Platelet activating factor: release from colonic mucosa in patients with ulcerative colitis and its effect on colonic secretion.

    PubMed Central

    Wardle, T D; Hall, L; Turnberg, L A

    1996-01-01

    Inflammatory mediators have been implicated in the pathophysiology of ulcerative colitis. They may stimulate intestinal secretion and contribute to the production of diarrhoea. Platelet activating factor (PAF) may be responsible for a high proportion of this secretory response. Biopsy specimens from inflamed and quiescent mucosa of patients with ulcerative colitis and normal human colonic mucosa were cultured or co-cultured. The release of PAF, prostaglandin E2, and leukotriene D4 into the culture medium was measured and the ability of this culture medium, from inflamed and normal tissues, to influence secretion in rat colonic mucosa was assessed. PAF was liberated by inflamed tissue. Its release from quiescent but not normal tissue was stimulated by medium in which inflamed mucosal biopsy tissues had been cultured and by exogenous bradykinin and 5-hydroxytryptamine, but not by histamine. PAF stimulated eicosanoid production. The rise in short circuit current produced in vitro by inflamed tissue culture medium was inhibited by the PAF receptor antagonist (CV 6209) (46%) (32.4 (2.9) v 17.5 (1.19) muA.cm-2, p < 0.005) and further by combined cyclooxygenase and lipoxygenase inhibition (indomethacin plus ICI 207968) (58%) (32.4 (2.9) v 13.6 (1.9) muA.cm-2, p < 0.005). Mepacrine and hydrocortisone attenuated considerably the electrical response evoked by medium from inflamed mucosa to a similar extent (32.4 (2.9) v 6.3 (1.2) v 5.1 (0.9) muA.cm-2, p < 0.001). These data suggest that PAF accounted for 46% of the culture medium secretory effect. Thus, any attempt to block its release in patients with ulcerative colitis may have only a partial effect on their symptoms. PMID:8675086

  7. Bioactive saponins and glycosides. IV. Four methyl-migrated 16,17-seco-dammarane triterpene gylcosides from Chinese natural medicine, hoveniae semen seu fructus, the seeds and fruit of Hovenia dulcis THUNB.: absolute stereostructures and inhibitory activity on histamine release of hovenidulciosides A1, A2, B1, and B2.

    PubMed

    Yoshikawa, M; Murakami, T; Ueda, T; Matsuda, H; Yamahara, J; Murakami, N

    1996-09-01

    Four bioactive methyl-migrated 16,17-seco-dammarane type triterpene glycosides called hovenidulciosides A1, A2, B1, and B2 were isolated from a Chinese natural medicine, Hoveniae Semen Seu Fructus, the seeds and fruit of Hovenia dulcis THUNB. (Rhamnaceae) together with hoduloside III and (+)-gallocatechin. The absolute stereostructures of hovenidulciosides A1, A2, B1, and B2 have been elucidated by chemical and physicochemical evidence. All were found to inhibit the histamine release from rat peritoneal exudate cells induced by compound 48/80 and calcium ionophore A-23187.

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

    PubMed

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

    2016-07-01

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

  9. The role of histamine degradation gene polymorphisms in moderating the effects of food additives on children's ADHD symptoms.

    PubMed

    Stevenson, Jim; Sonuga-Barke, Edmund; McCann, Donna; Grimshaw, Kate; Parker, Karen M; Rose-Zerilli, Matthew J; Holloway, John W; Warner, John O

    2010-09-01

    Food additives can exacerbate ADHD symptoms and cause non-immunoglobulin E-dependent histamine release from circulating basophils. However, children vary in the extent to which their ADHD symptoms are exacerbated by the ingestion of food additives. The authors hypothesized that genetic polymorphisms affecting histamine degradation would explain the diversity of responses to additives. In a double-blind, placebo-controlled crossover trial, challenges involving two food color additive and sodium benzoate (preservative) mixtures in a fruit drink were administered to a general community sample of 3-year-old children (N = 153) and 8/9-year-old children (N = 144). An aggregate ADHD symptom measure (based on teacher and parent blind ratings of behavior, blind direct observation of behavior in the classroom, and--for 8/9-year-old children only--a computerized measure of attention) was the main outcome variable. The adverse effect of food additives on ADHD symptoms was moderated by histamine degradation gene polymorphisms HNMT T939C and HNMT Thr105Ile in 3- and 8/9-year-old children and by a DAT1 polymorphism (short versus long) in 8/9-year-old children only. There was no evidence that polymorphisms in catecholamine genes COMT Val108Met, ADRA2A C1291G, and DRD4-rs7403703 moderated the effect on ADHD symptoms. Histamine may mediate the effects of food additives on ADHD symptoms, and variations in genes influencing the action of histamine may explain the inconsistency between previous studies. Genes influencing a range of neurotransmitter systems and their interplay with environmental factors, such as diet, need to be examined to understand genetic influences on ADHD symptoms.

  10. Stimulatory and inhibitory histamine receptors in canine cystic duct.

    PubMed Central

    Clanachan, A. S.; Courtney, D. F.; Scott, G. W.

    1982-01-01

    1 The effects of histamine receptor stimulation were assessed on the resistance of the canine cystic duct in vivo and on the contractility of circular muscle preparations of canine cystic duct in vitro. 2 In anaesthetized dogs, the H1-receptor agonist, 2-pyridylethylamine (0.05 to 15 mumol, i.a.), elicited dose-dependent increases in cystic duct resistance, whereas the H2-receptor agonist, 4-methylhistamine (0.05 to 15 mumol, i.a.) decreased cystic duct resistance. These responses were antagonized by the H1-receptor antagonist, diphenhydramine, and the H2-receptor antagonist, cimetidine, respectively. 3 Histamine (0.1 to 3000 nmol, i.a.) also increased cystic duct resistance in vivo. In the presence of diphenhydramine, the stimulatory effect of histamine was antagonized and slight decreases in cystic duct resistance became apparent. Cimetidine or prazosin also antagonized the stimulatory effects of histamine. 4 Histamine (1 to 100 microM) or 2-pyridylethylamine (1 to 100 microM) contracted, whereas 4-methylhistamine (1 to 100 microM) relaxed, circular muscle preparations of cystic duct. These excitatory and inhibitory responses were antagonized by diphenhydramine and cimetidine, respectively. 5 These results indicate that the canine cystic duct possesses excitatory H1- and inhibitory H2-receptors. The predominant effect of histamine is an H1-receptor-mediated increase in cystic duct resistance. Histamine, which may be released in association with cholecystitis, may exert significant effects on the regulation of bile flow in and out of the gallbladder and may contribute to gallbladder stasis during biliary disease. PMID:7150877

  11. Histamine H3 activation depresses cardiac function in experimental sepsis.

    PubMed

    Li, X; Eschun, G; Bose, D; Jacobs, H; Yang, J J; Light, R B; Mink, S N

    1998-11-01

    In the heart, histamine (H3) receptors may function as inhibitory presynaptic receptors that decrease adrenergic norepinephrine release in conditions of enhanced sympathetic neural activity. We hypothesized that H3-receptor blockade might improve cardiovascular function in sepsis. In a canine model of Escherichia coli sepsis, we found that H3-receptor blockade increased cardiac output (3.6 to 5.3 l/min, P < 0.05), systemic blood pressure (mean 76 to 96 mmHg, P < 0.05), and left ventricular contractility compared with pretreatment values. Plasma histamine concentrations increased modestly in the H3-blocker-sepsis group compared with values obtained in a nonsepsis-time-control group. In an in vitro preparation, histamine H3 activation could be identified under conditions of septic plasma. We conclude that activation of H3 receptors may contribute to cardiovascular collapse in sepsis.

  12. Conserved motifs in prokaryotic and eukaryotic polypeptide release factors: tRNA-protein mimicry hypothesis.

    PubMed Central

    Ito, K; Ebihara, K; Uno, M; Nakamura, Y

    1996-01-01

    Translation termination requires two codon-specific polypeptide release factors in prokaryotes and one omnipotent factor in eukaryotes. Sequences of 17 different polypeptide release factors from prokaryotes and eukaryotes were compared. The prokaryotic release factors share residues split into seven motifs. Conservation of many discrete, perhaps critical, amino acids is observed in eukaryotic release factors, as well as in the C-terminal portion of elongation factor (EF) G. Given that the C-terminal domains of EF-G interacts with ribosomes by mimicry of a tRNA structure, the pattern of conservation of residues in release factors may reflect requirements for a tRNA-mimicry for binding to the A site of the ribosome. This mimicry would explain why release factors recognize stop codons and suggests that all prokaryotic and eukaryotic release factors evolved from the progenitor of EF-G. Images Fig. 2 Fig. 3 PMID:8643594

  13. Arginine vasopressin potentiates adrenocorticotropin release induced by ovine corticotropin-releasing factor.

    PubMed Central

    DeBold, C R; Sheldon, W R; DeCherney, G S; Jackson, R V; Alexander, A N; Vale, W; Rivier, J; Orth, D N

    1984-01-01

    Arginine vasopressin (AVP) stimulates ACTH release in man and acts synergistically with synthetic ovine corticotropin-releasing factor (oCRF) in vitro. This study was designed to examine in man the combined effects of synthetic AVP (10 U intramuscularly) and oCRF (1 micrograms/kg intravenously) on ACTH release. Five normal male volunteers participated in five separate experiments: (a) AVP alone; (b) oCRF alone; (c) AVP followed by oCRF 15 min later; (d) simultaneous AVP and oCRF; and (e) insulin-induced hypoglycemia. Plasma immunoreactive ACTH (IR-ACTH) and IR-cortisol were measured for 4 h after injection of each hormone; basal levels for all subjects were less than or equal to 9 +/- 1.2 pg/ml and 4.9 +/- 0.4 micrograms/dl (mean +/- SE), respectively. AVP and oCRF, when given individually, caused rapid rises in IR-ACTH to similar peak levels of 25 +/- 6.6 and 33 +/- 4.6 pg/ml, respectively. AVP given 15 min before oCRF caused a 2.6-fold potentiation of the oCRF response, with a peak IR-ACTH of 85 +/- 4.6 pg/ml. AVP given at the same time as oCRF produced a fourfold potentiation of the peak IR-ACTH response to 132 +/- 11 pg/ml. These ACTH responses were far greater than those previously observed after 30-fold greater doses of oCRF alone. By way of comparison, insulin-induced hypoglycemia caused a peak IR-ACTH of 169 +/- 20 pg/ml. IR-ACTH returned to base line at 60-90 min after AVP alone, whereas the prolonged effect of oCRF was apparent whether it was given alone or in combination with AVP. The mean peak IR-cortisol responses to AVP, oCRF, and AVP given 15 min before oCRF were similar (16.5 +/- 0.9, 16.4 +/- 2.3, and 18.5 +/- 0.8 micrograms/dl, respectively), but the peak IR-cortisol responses to AVP and oCRF given simultaneously and to insulin-induced hypoglycemia were 1.5 and 1.7 times greater, respectively. IR-cortisol returned to base line within 2-3 h after AVP alone, but remained elevated for at least 4 h after oCRF alone or in combination with AVP. These

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

    PubMed

    Baintner, Károly

    2015-03-01

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

  15. Intrahypothalamic neuroendocrine actions of corticotropin-releasing factor.

    PubMed

    Almeida, O F; Hassan, A H; Holsboer, F

    1993-01-01

    Most studies of the neuroendocrine effects of corticotropin-releasing factor (CRF) have focused on its role in the regulation of the pituitary-adrenal axis; activation of this axis follows release of the peptide from CRF-containing terminals in the median eminence. However, a sizeable proportion of CRF fibres terminate within the hypothalamus itself, where synaptic contacts with other hypothalamic neuropeptidergic neurons (e.g. gonadotropin-releasing hormone-containing and opioidergic neurons) have been identified. Here, we summarize physiological and pharmacological data which provide insights into the nature and significance of these intrahypothalamic connections. It is now clear that CRF is a potent secretagogue of the three major endogenous opioid peptides (beta-endorphin, Met-enkephalin and dynorphin) and that it stimulates opioidergic neurons tonically. In the case of beta-endorphin, another hypothalamic peptide, arginine vasopressin, appears to be an essential mediator of CRF's effect, suggesting the occurrence of CRF synapses on, or in the vicinity of, vasopressin neurons; morphological support for this assumption is still wanting. Evidence for direct and indirect inhibitory effects of CRF on sexual behaviour and secretion of reproductive hormones is also presented; the indirect pathways include opioidergic neurons. An important conclusion from all these studies is that, in addition to its better known functions in producing adaptive responses during stressful situations, CRF might also contribute to the coordinated functioning of various components of the neuroendocrine system under basal conditions. Although feedback regulation of hypothalamic neuronal activity by peripheral steroids is a well-established tenet of endocrinology, data on modulation of the intrahypothalamic actions of CRF by adrenal and sex steroids are just emerging. Some of these newer findings may be useful in framing questions related to the mechanisms underlying disease states (such as

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

    PubMed

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

    2003-06-06

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

  17. Histamine suppresses epidermal keratinocyte differentiation and impairs skin barrier function in a human skin model

    PubMed Central

    Gschwandtner, M; Mildner, M; Mlitz, V; Gruber, F; Eckhart, L; Werfel, T; Gutzmer, R; Elias, P M; Tschachler, E

    2013-01-01

    Background Defects in keratinocyte differentiation and skin barrier are important features of inflammatory skin diseases like atopic dermatitis. Mast cells and their main mediator histamine are abundant in inflamed skin and thus may contribute to disease pathogenesis. Methods Human primary keratinocytes were cultured under differentiation-promoting conditions in the presence and absence of histamine, histamine receptor agonists and antagonists. The expression of differentiation-associated genes and epidermal junction proteins was quantified by real-time PCR, Western blot, and immunofluorescence labeling. The barrier function of human skin models was tested by the application of biotin as tracer molecule. Results The addition of histamine to human keratinocyte cultures and organotypic skin models reduced the expression of the differentiation-associated proteins keratin 1/10, filaggrin, and loricrin by 80–95%. Moreover, the addition of histamine to skin models resulted in the loss of the granular layer and thinning of the epidermis and stratum corneum by 50%. The histamine receptor H1R agonist, 2-pyridylethylamine, suppressed keratinocyte differentiation to the same extent as did histamine. Correspondingly, cetirizine, an antagonist of H1R, virtually abrogated the effect of histamine. The expression of tight junction proteins zona occludens-1, occludin, claudin-1, and claudin-4, as well as that of desmosomal junction proteins corneodesmosin and desmoglein-1, was down-regulated by histamine. The tracer molecule biotin readily penetrated the tight junction barrier of skin cultures grown in the presence of histamine, while their diffusion was completely blocked in nontreated controls. Conclusions Our findings suggest a new mechanism by which mast cell activation and histamine release contribute to skin barrier defects in inflammatory skin diseases. PMID:23157658

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

    PubMed

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

    2014-12-01

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

  19. Sugarcane transgenics expressing MYB transcription factors show improved glucose release.

    PubMed

    Poovaiah, Charleson R; Bewg, William P; Lan, Wu; Ralph, John; Coleman, Heather D

    2016-01-01

    Sugarcane, a tropical C4 perennial crop, is capable of producing 30-100 tons or more of biomass per hectare annually. The lignocellulosic residue remaining after sugar extraction is currently underutilized and can provide a significant source of biomass for the production of second-generation bioethanol. MYB31 and MYB42 were cloned from maize and expressed in sugarcane with and without the UTR sequences. The cloned sequences were 98 and 99 % identical to the published nucleotide sequences. The inclusion of the UTR sequences did not affect any of the parameters tested. There was little difference in plant height and the number of internodes of the MYB-overexpressing sugarcane plants when compared with controls. MYB transgene expression determined by qPCR exhibited continued expression in young and maturing internodes. MYB31 downregulated more genes within the lignin biosynthetic pathway than MYB42. MYB31 and MYB42 expression resulted in decreased lignin content in some lines. All MYB42 plants further analyzed showed significant increases in glucose release by enzymatic hydrolysis in 72 h, whereas only two MYB31 plants released more glucose than control plants. This correlated directly with a significant decrease in acid-insoluble lignin. Soluble sucrose content of the MYB42 transgenic plants did not vary compared to control plants. This study demonstrates the use of MYB transcription factors to improve the production of bioethanol from sugarcane bagasse remaining after sugar extraction.

  20. Sugarcane transgenics expressing MYB transcription factors show improved glucose release

    DOE PAGES

    Poovaiah, Charleson R.; Bewg, William P.; Lan, Wu; ...

    2016-07-15

    In this study, sugarcane, a tropical C4 perennial crop, is capable of producing 30-100 tons or more of biomass per hectare annually. The lignocellulosic residue remaining after sugar extraction is currently underutilized and can provide a significant source of biomass for the production of second-generation bioethanol. As a result, MYB31 and MYB42 were cloned from maize and expressed in sugarcane with and without the UTR sequences. The cloned sequences were 98 and 99 % identical to the published nucleotide sequences. The inclusion of the UTR sequences did not affect any of the parameters tested. There was little difference in plantmore » height and the number of internodes of the MYB-overexpressing sugarcane plants when compared with controls. MYB transgene expression determined by qPCR exhibited continued expression in young and maturing internodes. MYB31 downregulated more genes within the lignin biosynthetic pathway than MYB42. MYB31 and MYB42 expression resulted in decreased lignin content in some lines. All MYB42 plants further analyzed showed significant increases in glucose release by enzymatic hydrolysis in 72 h, whereas only two MYB31 plants released more glucose than control plants. This correlated directly with a significant decrease in acid-insoluble lignin. Soluble sucrose content of the MYB42 transgenic plants did not vary compared to control plants. In conclusion, this study demonstrates the use of MYB transcription factors to improve the production of bioethanol from sugarcane bagasse remaining after sugar extraction.« less

  1. Progress in corticotropin-releasing factor-1 antagonist development

    PubMed Central

    Zorrilla, Eric P.; Koob, George F.

    2010-01-01

    Corticotropin-releasing factor (CRF) receptor antagonists have been sought since the stress-secreted peptide was isolated in 1981. Although evidence suggests the limited efficacy of CRF1 antagonists as antidepressants, CRF1 antagonists might be novel pharmacotherapies for anxiety and addiction. Progress in understanding the two-domain model of ligand–receptor interactions for CRF family receptors might yield chemically novel CRF1 receptor antagonists, including peptide CRF1 antagonists, antagonists with signal transduction selectivity and nonpeptide CRF1 antagonists that act via the extracellular (rather than transmembrane) domains. Novel ligands that conform to prevalent pharmacophore and exhibit drug-like pharmacokinetic properties have been identified. The therapeutic utility of CRF1 antagonists should soon be clearer: several small molecules are currently in Phase II/III clinical trials for depression, anxiety and irritable bowel syndrome. PMID:20206287

  2. Differential modulation of excitatory and inhibitory striatal synaptic transmission by histamine.

    PubMed

    Ellender, Tommas J; Huerta-Ocampo, Icnelia; Deisseroth, Karl; Capogna, Marco; Bolam, J Paul

    2011-10-26

    Information processing in the striatum is critical for basal ganglia function and strongly influenced by neuromodulators (e.g., dopamine). The striatum also receives modulatory afferents from the histaminergic neurons in the hypothalamus which exhibit a distinct diurnal rhythm with high activity during wakefulness, and little or no activity during sleep. In view of the fact that the striatum also expresses a high density of histamine receptors, we hypothesized that released histamine will affect striatal function. We studied the role of histamine on striatal microcircuit function by performing whole-cell patch-clamp recordings of neurochemically identified striatal neurons combined with electrical and optogenetic stimulation of striatal afferents in mouse brain slices. Bath applied histamine had many effects on striatal microcircuits. Histamine, acting at H(2) receptors, depolarized both the direct and indirect pathway medium spiny projection neurons (MSNs). Excitatory, glutamatergic input to both classes of MSNs from both the cortex and thalamus was negatively modulated by histamine acting at presynaptic H(3) receptors. The dynamics of thalamostriatal, but not corticostriatal, synapses were modulated by histamine leading to a facilitation of thalamic input. Furthermore, local inhibitory input to both classes of MSNs was negatively modulated by histamine. Subsequent dual whole-cell patch-clamp recordings of connected pairs of striatal neurons revealed that only lateral inhibition between MSNs is negatively modulated, whereas feedforward inhibition from fast-spiking GABAergic interneurons onto MSNs is unaffected by histamine. These findings suggest that the diurnal rhythm of histamine release entrains striatal function which, during wakefulness, is dominated by feedforward inhibition and a suppression of excitatory drive.

  3. Histamine-HisCl1 Receptor Axis Regulates Wake-Promoting Signals in Drosophila melanogaster

    PubMed Central

    Oh, Yangkyun; Jang, Donghoon; Sonn, Jun Young; Choe, Joonho

    2013-01-01

    Histamine and its two receptors, histamine-gated chloride channel subunit 1 (HisCl1) and ora transientless (Ort), are known to control photoreception and temperature sensing in Drosophila. However, histamine signaling in the context of neural circuitry for sleep-wake behaviors has not yet been examined in detail. Here, we obtained mutant flies with compromised or enhanced histamine signaling and tested their baseline sleep. Hypomorphic mutations in histidine decarboxylase (HDC), an enzyme catalyzing the conversion from histidine to histamine, caused an increase in sleep duration. Interestingly, hisCl1 mutants but not ort mutants showed long-sleep phenotypes similar to those in hdc mutants. Increased sleep duration in hisCl1 mutants was rescued by overexpressing hisCl1 in circadian pacemaker neurons expressing a neuropeptide pigment dispersing factor (PDF). Consistently, RNA interference (RNAi)-mediated depletion of hisCl1 in PDF neurons was sufficient to mimic hisCl1 mutant phenotypes, suggesting that PDF neurons are crucial for sleep regulation by the histamine-HisCl1 signaling. Finally, either hisCl1 mutation or genetic ablation of PDF neurons dampened wake-promoting effects of elevated histamine signaling via direct histamine administration. Taken together, these data clearly demonstrate that the histamine-HisCl1 receptor axis can activate and maintain the wake state in Drosophila and that wake-activating signals may travel via the PDF neurons. PMID:23844178

  4. Blood histamine concentrations are not elevated in humans with septic shock

    SciTech Connect

    Jacobs, R.; Kaliner, M.; Shelhamer, J.H.; Parrillo, J.E.

    1989-01-01

    Histamine has been suggested as an important mediator of the cardiovascular abnormalities during septic shock. To determine if blood histamine levels were increased during human sepsis and septic shock, plasma histamine was measured using a very sensitive radioenzyme assay employing histamine N-methyltransferase (HNMT) in the following patient groups: normal controls (n = 76), nonseptic critically ill (n = 12), nonseptic shock (n = 2), sepsis without shock (n = 28), and septic shock (n = 41). Using this enzyme binding assay, all these groups had similar, normal plasma histamine concentrations, except those patients with septic shock whose mean histamine measurements were significantly reduced (p less than .002). This decrease was found to be due to an artifact of the assay: plasma contained a circulating inhibitor that falsely lowered the measured histamine level. Fractionation of septic shock plasma using molecular exclusion membranes and gel filtration revealed a 5000 MW inhibitory factor. After removal of this inhibitor from plasma, septic shock plasma histamine levels were normal. Thus, septic shock patients may have a circulating inhibitor of the HNMT enzyme, but plasma histamine concentrations are normal. Histaminemia is unlikely to play an important role in the pathogenesis of septic shock in humans.

  5. Measurement of urinary histamine: comparison of fluorometric and radioisotopic-enzymatic assay procedures

    SciTech Connect

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

    1982-02-01

    Assessment of urinary histamine may prove useful in determining the role of histamine in human health and disease. Urinary histamine may be accurately estimated by a modified fluorometric assay employing diamine oxidase (DAO) digestion and cation-exchange chromatography. Normal urine histamine values obtained by this assay are: arithmetic means (+/- SEM), 8.6 +/- 0.6 ng/ml and 10.5 +/- 0.7 micrograms/24 hr; geometric means (+/- SEM), 6.2 +/- 1.1 ng/ml and 10.0 +/- 1.3 micrograms/24 hr. However, the radioisotopic-enzymatic assay is less expensive, easier to perform, and possibly more sensitive. Therefore the two procedures were compared. The radioenzyme assay was found to be affected by factors in urine (possibly salt concentrations) requiring extraction of histamine from urine by butanol-heptane. Moreover, it was found to be necessary to compare DAO-digested samples with undigested samples to accurately estimate histamine levels and to run the standard curve of histamine in DAO-digested urine. Even with these modifications, the radioenzyme assay was not as accurate as the fluorometric assay for urine samples having histamine values about 60 ng/ml. Therefore we recommend utilization of the modified fluorometric assay for the measurement of urinary histamine levels.

  6. Regulation of plasma histamine levels by the mast cell clock and its modulation by stress

    PubMed Central

    Nakamura, Yuki; Ishimaru, Kayoko; Shibata, Shigenobu; Nakao, Atsuhito

    2017-01-01

    At steady state, plasma histamine levels exhibit circadian variations with nocturnal peaks, which is implicated in the nighttime exacerbation of allergic symptoms. However, the regulatory mechanisms are largely unexplored. This study determined how steady-state plasma histamine levels are regulated and affected by environmental factors. We found that plasma histamine levels decreased in mast cell–deficient mice and their circadian variations were lost in mast cell–deficient mice reconstituted with bone marrow–derived mast cells (BMMCs) harboring a mutation in the circadian gene Clock. Clock temporally regulates expression of organic cation transporter 3 (OCT3), which is involved in histamine transport, in mast cells; OCT inhibition abolished circadian variations in plasma histamine levels. Mice housed under aberrant light/dark conditions or suffering from restraint stress exhibited de-synchronization of the mast cell clockwork, concomitant with the loss of circadian variations in OCT3 expression and plasma histamine levels. The degree of compound 48/80–induced plasma extravasation in mice was correlated with plasma histamine levels. Collectively, the mast cell clock mediates circadian regulation of plasma histamine levels at steady state, in part by controlling OCT3 expression, which can be modulated by stress. Additionally, we propose that plasma histamine levels potentiate mast cell–mediated allergic reactions. PMID:28074918

  7. Suppression of rat stomach histidine decarboxylase activity by histamine: H2-receptor-mediated feed-back

    PubMed Central

    Håkanson, R.; Larsson, L.-I.; Liedberg, G.; Rehfeld, J. F.; Sundler, F.

    1977-01-01

    1. Gastrin activates rat stomach histidine decarboxylase. Exogenous histamine suppressed the basal enzyme activity in unoperated, in nephrectomized, in vagally denervated and in antrectomized rats, and counteracted the pentagastrin-induced enzyme activation in unoperated rats. 2. Kinetic analysis of enzyme-catalysed histidine decarboxylation in extracts from untreated vagotomized and from histamine-treated vagotomized rats showed that the histamine-induced suppression of histidine decarboxylase activity probably reflects a reduced enzyme concentration. Moreover, the enzyme half-life in vagotomized rats after treatment with histamine was shorter than the half-life observed after inhibition of enzyme synthesis. These observations suggest that administration of histamine not only inhibits enzyme synthesis but also causes an accelerated rate of elimination of histidine decarboxylase. 3. Intravenous infusion of histamine caused marked displacement of the pentagastrin dose—response curve, in a manner suggesting a reduced sensitivity to pentagastrin. 4. After H2-receptor blockade, but not after H1-receptor blockade, histamine was less effective in suppressing the enzyme activity. Furthermore, H2-receptor blockade augmented the pentagastrin-induced enzyme activation. 5. The results suggest that histamine (via H2-receptors) reduces the sensitivity of the histamine-storing cells to gastrin and that H2-receptor blockade induces the opposite effects. 6. We propose that the histamine-storing cells in the rat stomach are endowed with H2-receptors and that exogenous histamine is capable of acting directly on the histamine cells. This may reflect a physiological control mechanism whereby mobilized endogenous histamine modifies its own synthesis and release. PMID:894608

  8. Physicochemical characterization of cytostatic factors released from human monocytes.

    PubMed Central

    Nissen-Meyer, J; Hammerstrøm, J

    1982-01-01

    Cultured human monocytes released cytostatic activity upon in vitro activation with lymphokines and lipopolysaccharide. This activity was mainly due to the presence of two different cytostatic factors, termed CstF I and II, which were separated by ion-exchange chromatography. At neutral pH, CstF I bound to the weak anion exchanger DEAE-Sephacel but not to the weak cation exchanger CM-Sepharose, whereas CstF II bound to CM-Sepharose but not to DEAE-Sephacel. The molecular weights of CstF I and II as determined by gel filtration were 55,000 and 40,000, respectively. Upon chromatofocusing, CstF I behaved as if it had an isoelectric point of 5.3. Neither CstF I nor CstF II bound specifically to concanavalin A-Sepharose, indicating the absence of carbohydrate residues containing alpha-D-mannopyranosyl, alpha-D-glucopyranosyl, or sterically related components. Both factors were susceptible to inactivation by proteinase K, demonstrating their protein nature. CstF II was purified more than 3,000-fold upon chromatography on CM-Sepharose and Sephacryl S-200. Ion-exchange chromatography and chromatofocusing of CstF I removed 97% of the proteins in the monocyte supernatant, but only 15% of the activity was recovered, resulting in a fivefold purification of CstF I. PMID:7141697

  9. Corticotropin releasing factor (CRF): immunocytochemical localization and radioimmunoassay (RIA). [Rats

    SciTech Connect

    Vigh, S.; Merchenthaler, I.; Torres-Aleman, I.; Sueiras-Diaz, J.; Coy, D.; Carter, W.H.; Petrusz, P.; Schally, A.V.

    1982-11-29

    Two fragments of the amino acid sequence corresponding to ovine corticotropin releasing factor (CRF 37-41 and CRF 22-41), as well as the full sequence of 41 residues (CRF 1-41), synthesized in our laboratories by solid-phase methods, were coupled to bovine serum albumin (BSA) with glutaraldehyde. New Zealand white rabbits were immunized with the emulsified mixtures of peptide-BSA conjugates and Freund's adjuvant as immunogens. The specificity of the generated antibodies was studied by agar-gel diffusion, absorption tests in the immunohistochemical system, and with the aid of displacement curves in RIA. /sup 125/I-Tyr(35)-CRF 36-41 and /sup 125/I-Tyr(0)-CRF 1-41 were used as radioligands in the RIA. The minimum detectable dose was 20 pg. The linearity observed in RIA for immunoreactive CRF in extracts of rat hypothalami, together with the immunocytochemical findings in the rat brain, indicate the presence of substance(s) immunologically indistinguishable from CRF. Immunohistochemistry with the peroxidase-antiperoxidase (PAP) technique detected the following CRF-immunoreactive structures in vibratome sections of hypothalami of colchicine-treated rats: CRF-containing cell bodies were observed mainly in smaller neurons of the paraventricular nucleus. CRF-positive nerve fibers and/or terminals were present in the external zone of the median eminence, with some immunoreactive CRF also present in the internal zone. The CRF-positive terminals were localized in the central regions of the median eminence. Data reinforce the view that this polypeptide plays a physiological role in the control of ACTH release.

  10. Sugarcane transgenics expressing MYB transcription factors show improved glucose release

    SciTech Connect

    Poovaiah, Charleson R.; Bewg, William P.; Lan, Wu; Ralph, John; Coleman, Heather D.

    2016-07-15

    In this study, sugarcane, a tropical C4 perennial crop, is capable of producing 30-100 tons or more of biomass per hectare annually. The lignocellulosic residue remaining after sugar extraction is currently underutilized and can provide a significant source of biomass for the production of second-generation bioethanol. As a result, MYB31 and MYB42 were cloned from maize and expressed in sugarcane with and without the UTR sequences. The cloned sequences were 98 and 99 % identical to the published nucleotide sequences. The inclusion of the UTR sequences did not affect any of the parameters tested. There was little difference in plant height and the number of internodes of the MYB-overexpressing sugarcane plants when compared with controls. MYB transgene expression determined by qPCR exhibited continued expression in young and maturing internodes. MYB31 downregulated more genes within the lignin biosynthetic pathway than MYB42. MYB31 and MYB42 expression resulted in decreased lignin content in some lines. All MYB42 plants further analyzed showed significant increases in glucose release by enzymatic hydrolysis in 72 h, whereas only two MYB31 plants released more glucose than control plants. This correlated directly with a significant decrease in acid-insoluble lignin. Soluble sucrose content of the MYB42 transgenic plants did not vary compared to control plants. In conclusion, this study demonstrates the use of MYB transcription factors to improve the production of bioethanol from sugarcane bagasse remaining after sugar extraction.

  11. Azelastine is more potent than olopatadine n inhibiting interleukin-6 and tryptase release from human umbilical cord blood-derived cultured mast cells.

    PubMed

    Kempuraj, Duraisamy; Huang, Man; Kandere, Kristiana; Boucher, William; Letourneau, Richard; Jeudy, Sheila; Fitzgerald, Kim; Spear, Kathleen; Athanasiou, Achilles; Theoharides, Theoharis C

    2002-05-01

    Mast cells are involved in early- and late-phase reactions by releasing vasoactive molecules, proteases, and cytokines. Certain histamine-1 receptor antagonists and other antiallergic drugs seem to inhibit the release of mediators from rat and human mast cells. Azelastine and olopatadine are antiallergic agents present in the ophthalmic solutions azelastine hydrochloride (Optivar, Asta Medica/Muro Pharmaceuticals, Tewksbury, MA), and olopatadine hydrochloride (Patanol, Alcon Laboratories, Fort Worth, TX), respectively. We investigated the effect of these drugs on interleukin-6 (IL-6), tryptase, and histamine release from cultured human mast cells (CHMCs). CHMCs were grown from human umbilical cord blood-derived CD34+ cells in the presence of stem cell factor and IL-6 for 14 to 16 weeks. Sensitized CHMCs were pretreated with various concentrations of azelastine or olopatadine for 5 minutes. CHMCs were then challenged with anti-immunoglobulin E, and the released mediators were quantitated. The greatest inhibition of mediator release was seen with 24 microM azelastine; this level of inhibition was matched with the use of 133 microM olopatadine. At this concentration, these drugs inhibited IL-6 release by 83% and 74%, tryptase release by 55% and 79%, and histamine release by 41% and 45%, respectively. Activated CHMCs were characterized by numerous filopodia that were inhibited by both drugs as shown by electron microscopy. These results indicate that azelastine and olopatadine can inhibit CHMCs activation and release of IL-6, tryptase, and histamine. On an equimolar basis, azelastine was a more potent inhibitor than olopatadine.

  12. The interaction of calcium and strontium with phosphatidyl serine in the anaphylactic secretion of histamine

    PubMed Central

    Foreman, J. C.; Mongar, J. L.

    1973-01-01

    1. Spontaneous histamine release from isolated mast cells was found to be independent of calcium in the concentration range up to 1 m-mole/l. Phosphatidyl serine did not change the effect of calcium on spontaneous release. 2. Spontaneous histamine release was found to vary with the strontium ion concentration. Graded increase in the release occurred as the concentration of strontium was raised from 1 to 10 m-mole/l. Phosphatidyl serine potentiated this action of strontium; the potentiation showed a graded increase as the phosphatidyl serine concentration was raised from 1 to 100 μg/ml. 3. The activation of anaphylactic histamine release by calcium was potentiated by phosphatidyl serine; the degree of potentiation showed a graded increase as the calcium concentration was raised from 0·1 to 1·0 m-mole/l. 4. The activation of anaphylactic histamine release by strontium showed little, if any, potentiation by phosphatidyl serine. 5. The response of the mast cells, in terms of anaphylactic histamine release, to calcium, in the presence of optimal concentrations of phosphatidyl serine, was found to be similar to that observed in the presence of strontium alone. 6. These observations are discussed in terms of the concepts of affinity and efficacy of the ions at their receptor sites. PMID:4122664

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

    PubMed

    Varty, LoriAnn M; Hey, John A

    2002-10-11

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

  14. Conformational thermostabilisation of corticotropin releasing factor receptor 1

    PubMed Central

    Kean, James; Bortolato, Andrea; Hollenstein, Kaspar; Marshall, Fiona H.; Jazayeri, Ali

    2015-01-01

    Recent technical advances have greatly facilitated G-protein coupled receptors crystallography as evidenced by the number of successful x-ray structures that have been reported recently. These technical advances include novel detergents, specialised crystallography techniques as well as protein engineering solutions such as fusions and conformational thermostabilisation. Using conformational thermostabilisation, it is possible to generate variants of GPCRs that exhibit significantly increased stability in detergent micelles whilst preferentially occupying a single conformation. In this paper we describe for the first time the application of this technique to a member of a class B GPCR, the corticotropin releasing factor receptor 1 (CRF1R). Mutational screening in the presence of the inverse agonist, CP-376395, resulted in the identification of a construct with twelve point mutations that exhibited significantly increased thermal stability in a range of detergents. We further describe the subsequent construct engineering steps that eventually yielded a crystallisation-ready construct which recently led to the solution of the first x-ray structure of a class B receptor. Finally, we have used molecular dynamic simulation to provide structural insight into CRF1R instability as well as the stabilising effects of the mutants, which may be extended to other class B receptors considering the high degree of structural conservation. PMID:26159865

  15. Class I release factors in ciliates with variant genetic codes

    PubMed Central

    Inagaki, Yuji; Doolittle, W. Ford

    2001-01-01

    In eukaryotes with the universal genetic code a single class I release factor (eRF1) most probably recognizes all stop codons (UAA, UAG and UGA) and is essential for termination of nascent peptide synthesis. It is well established that stop codons have been reassigned to amino acid codons at least three times among ciliates. The codon specificities of ciliate eRF1s must have been modified to accommodate the variant codes. In this study we have amplified, cloned and sequenced eRF1 genes of two hypotrichous ciliates, Oxytricha trifallax (UAA and UAG for Gln) and Euplotes aediculatus (UGA for Cys). We also sequenced/identified three protist and two archaeal class I RF genes to enlarge the database of eRF1/aRF1s with the universal code. Extensive comparisons between universal code eRF1s and those of Oxytricha, Euplotes and Tetrahymena, which represent three lineages that acquired variant codes independently, provide important clues to identify stop codon-binding regions in eRF1. Domain 1 in the five ciliate eRF1s, particulary the TASNIKS heptapeptide and its adjacent region, differs significantly from domain 1 in universal code eRF1s. This observation suggests that domain 1 contains the codon recognition site, but that the mechanism of eRF1 codon recognition may be more complex than proposed by Nakamura et al. or Knight and Landweber. PMID:11160924

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

    PubMed

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

    2016-04-01

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

  17. Corticotropin Releasing Factor promotes breast cancer cell motility and invasiveness

    PubMed Central

    Androulidaki, Ariadne; Dermitzaki, Erini; Venihaki, Maria; Karagianni, Effie; Rassouli, Olga; Andreakou, Erini; Stournaras, Christos; Margioris, Andrew N; Tsatsanis, Christos

    2009-01-01

    Introduction Cancer cells secrete bioactive peptides that act in an autocrine or paracrine fashion affecting tumor growth and metastasis. Corticotropin-releasing factor (CRF), a hypothalamic neuropeptide that controls the response to stress, has been detected in breast cancer tissues and cell lines. CRF can affect breast cancer cells in an autocrine or paracrine manner via its production from innervating sympathetic neurons or immune cells. Methods In the present study we report our findings regarding the impact of CRF on breast cancer cell motility and invasiveness. For this purpose we used the MCF7 breast cancer cell line and evaluated the effect of CRF on motility and invasiveness using the wound-healing and boyden-chamber assays. In addition, we measured the effect of CRF on molecules that mediate motility by western blot, immunofluorescence, ELISA and RT-PCR. Results Our findings show that: 1. CRF transiently inhibited the apoptosis of MCF7 cells. 2. CRF enhanced MCF7 cell motility in a wound healing assay and their invasiveness through extracellular matrix. 3. CRF increased actin polymerization, phosphorylation of Focal Adhesion Kinase (FAK), providing a potential mechanism for the observed induction of MCF7 motility. 4. CRF induced the expression of Cox-1 but not Cox-2 in MCF7 cells as well as the production of prostaglandins, factors known to promote invasiveness and metastasis. Conclusion Overall, our data suggest that CRF stimulates cell motility and invasiveness of MCF7 cells most probably via induction of FAK phosphorylation and actin filament reorganization and production of prostaglandins via Cox1. Based on these findings we postulate that the stress neuropeptide CRF present in the vicinity of tumors (either produced locally by the tumor cells themselves or by nearby normal cells or secreted from the innervations of surrounding tissues) may play an important role on breast tumor growth and metastatic capacity, providing a potential link between stress

  18. Carnosine protects against NMDA-induced neurotoxicity in differentiated rat PC12 cells through carnosine-histidine-histamine pathway and H(1)/H(3) receptors.

    PubMed

    Shen, Yao; Hu, Wei-Wei; Fan, Yan-Yin; Dai, Hai-Bing; Fu, Qiu-Li; Wei, Er-Qing; Luo, Jian-Hong; Chen, Zhong

    2007-03-01

    Since the histidine-containing dipeptide carnosine (beta-alanyl-L-histidine) is believed to have many physiological functions in the brain, we investigated the neuroprotective effects of carnosine and its mechanisms of action in an in vitro model of neurotoxicity induced by N-methyl-d-aspartate (NMDA) in differentiated PC12 cells. Pretreatment with carnosine increased the viability and decreased the number of apoptotic and necrotic cells measured by MTT and Hoechst 33342 and propidium iodide (PI) double staining assays. Carnosine also can inhibit the glutamate release and increase HDC activity and the intracellular and extracellular contents of carnosine, histidine and histamine detected by high-performance liquid chromatography (HPLC). The protection by carnosine was reversed by alpha- fluoromethylhistidine, a selective and irreversible inhibitor of histidine decarboxylase (HDC). Pyrilamine and thioperamide, selective central histamine H(1) and H(3) antagonists also significantly reversed the protection of carnosine. Further, the inhibition of glutamate release by carnosine was reversed by thioperamide. Therefore, the protective mechanism of carnosine may not only involve the carnosine-histidine-histamine pathway, but also H(1)/H(3) receptors and the effective inhibition of glutamate release. This study indicates that carnosine may be an endogenous protective factor and calls for its further study as a new antiexcitotoxic agent.

  19. Anti histaminic activity of cissus quadragularis.

    PubMed

    Begum, V H; Sadique, J

    1999-01-01

    Anti histaminic activity of cissus quadrangularis stem powder was carried out determining the histamine activity and histamine content in carrageenin induced rat paw swelling model and formalin induced peritonitis respectively. The crude powder at the dose of 100mg/1QQ00 gm exerted reduction to the maximum of 44% in the early hisamine phase swelling. Further it significantly reduced the histamine content in the peritoneal fluid. For comparison standard steroidal drug hydrocortisone and avil were used.

  20. Histamine reduces flash sensitivity of on ganglion cells in the primate retina.

    PubMed

    Akimov, Nikolay P; Marshak, David W; Frishman, Laura J; Glickman, Randolph D; Yusupov, Rafail G

    2010-07-01

    PURPOSE. In Old World primates, the retina receives input from histaminergic neurons in the posterior hypothalamus. They are a subset of the neurons that project throughout the central nervous system and fire maximally during the day. The contribution of these neurons to vision, was examined by applying histamine to a dark-adapted, superfused baboon eye cup preparation while making extracellular recordings from peripheral retinal ganglion cells. METHODS. The stimuli were 5-ms, 560-nm, weak, full-field flashes in the low scotopic range. Ganglion cells with sustained and transient ON responses and two cell types with OFF responses were distinguished; their responses were recorded with a 16-channel microelectrode array. RESULTS. Low micromolar doses of histamine decreased the rate of maintained firing and the light sensitivity of ON ganglion cells. Both sustained and transient ON cells responded similarly to histamine. There were no statistically significant effects of histamine in a more limited study of OFF ganglion cells. The response latencies of ON cells were approximately 5 ms slower, on average, when histamine was present. Histamine also reduced the signal-to-noise ratio of ON cells, particularly in those cells with a histamine-induced increase in maintained activity. CONCLUSIONS. A major action of histamine released from retinopetal axons under dark-adapted conditions, when rod signals dominate the response, is to reduce the sensitivity of ON ganglion cells to light flashes. These findings may relate to reports that humans are less sensitive to light stimuli in the scotopic range during the day, when histamine release in the retina is expected to be at its maximum.

  1. Histamine Reduces Flash Sensitivity of ON Ganglion Cells in the Primate Retina

    PubMed Central

    Akimov, Nikolay P.; Marshak, David W.; Frishman, Laura J.; Yusupov, Rafail G.

    2010-01-01

    Purpose. In Old World primates, the retina receives input from histaminergic neurons in the posterior hypothalamus. They are a subset of the neurons that project throughout the central nervous system and fire maximally during the day. The contribution of these neurons to vision, was examined by applying histamine to a dark-adapted, superfused baboon eye cup preparation while making extracellular recordings from peripheral retinal ganglion cells. Methods. The stimuli were 5-ms, 560-nm, weak, full-field flashes in the low scotopic range. Ganglion cells with sustained and transient ON responses and two cell types with OFF responses were distinguished; their responses were recorded with a 16-channel microelectrode array. Results. Low micromolar doses of histamine decreased the rate of maintained firing and the light sensitivity of ON ganglion cells. Both sustained and transient ON cells responded similarly to histamine. There were no statistically significant effects of histamine in a more limited study of OFF ganglion cells. The response latencies of ON cells were approximately 5 ms slower, on average, when histamine was present. Histamine also reduced the signal-to-noise ratio of ON cells, particularly in those cells with a histamine-induced increase in maintained activity. Conclusions. A major action of histamine released from retinopetal axons under dark-adapted conditions, when rod signals dominate the response, is to reduce the sensitivity of ON ganglion cells to light flashes. These findings may relate to reports that humans are less sensitive to light stimuli in the scotopic range during the day, when histamine release in the retina is expected to be at its maximum. PMID:20207974

  2. Inhibition of mast cell-derived histamine secretion by cromolyn sodium treatment decreases biliary hyperplasia in cholestatic rodents.

    PubMed

    Kennedy, Lindsey L; Hargrove, Laura A; Graf, Allyson B; Francis, Taylor C; Hodges, Kyle M; Nguyen, Quy P; Ueno, Yoshi; Greene, John F; Meng, Fanyin; Huynh, Victoria D; Francis, Heather L

    2014-12-01

    Cholangiopathies are characterized by dysregulation of the balance between biliary growth and loss. We have shown that histamine (HA) stimulates biliary growth via autocrine mechanisms. To evaluate the paracrine effects of mast cell (MC) stabilization on biliary proliferation, sham or BDL rats were treated by IP-implanted osmotic pumps filled with saline or cromolyn sodium (24 mg/kg BW/day (inhibits MC histamine release)) for 1 week. Serum, liver blocks and cholangiocytes were collected. Histidine decarboxylase (HDC) expression was measured using real-time PCR in cholangiocytes. Intrahepatic bile duct mass (IBDM) was evaluated by IHC for CK-19. MC number was determined using toluidine blue staining and correlated to IBDM. Proliferation was evaluated by PCNA expression in liver sections and purified cholangiocytes. We assessed apoptosis using real-time PCR and IHC for BAX. Expression of MC stem factor receptor, c-kit, and the proteases chymase and tryptase were measured by real-time PCR. HA levels were measured in serum by EIA. In vitro, MCs and cholangiocytes were treated with 0.1% BSA (basal) or cromolyn (25 μM) for up to 48 h prior to assessing HDC expression, HA levels and chymase and tryptase expression. Supernatants from MCs treated with or without cromolyn were added to cholangiocytes before measuring (i) proliferation by MTT assays, (ii) HDC gene expression by real-time PCR and (iii) HA release by EIA. In vivo, cromolyn treatment decreased BDL-induced: (i) IBDM, MC number, and biliary proliferation; (ii) HDC and MC marker expression; and (iii) HA levels. Cromolyn treatment increased cholangiocyte apoptosis. In vitro, cromolyn decreased HA release and chymase and tryptase expression in MCs but not in cholangiocytes. Cromolyn-treated MC supernatants decreased biliary proliferation and HA release. These studies provide evidence that MC histamine is key to biliary proliferation and may be a therapeutic target for the treatment of cholangiopathies.

  3. Tumor necrosis factor-mediated release of platelet-derived growth factor from cultured endothelial cells

    PubMed Central

    1987-01-01

    Platelet-derived growth factor (PDGF) is a 30,000-Mr glycoprotein that is chemotactic and mitogenic for vascular smooth muscle cells (SMC). It is also a potent vasoconstrictor. In the present study, we found that the macrophage-derived polypeptide, tumor necrosis factor (TNF), releases a factor from human umbilical vein endothelial cells (EC) that is mitogenic for SMC. Postculture medium from TNF-stimulated EC induced a 90% increase in mitogenesis is compared with controls. This effect was half-maximal at a TNF dose of 114 pM, reflected a 2.5-fold increase in PDGF-specific mRNA synthesis, and peaked at 15 h of TNF stimulation. Mitogenic activity was completely abrogated by preincubation of postculture medium with antibody to platelet PDGF. Stimulation of EC with IL-1 (60-240 pM) led to the release of similar mitogenic activity. Thus, in addition to its effects on the hemostatic and adhesive properties of EC, TNF also promotes release of PDGF, which may serve to modulate proliferation of vascular SMC during wound healing, inflammation, and atherogenesis. PMID:3598461

  4. In vivo effects of corticotropin-releasing factor in pregnant rats.

    PubMed

    Jain, V; Shi, S Q; Vedernikov, Y P; Saade, G R; Chwalisz, K; Garfield, R E

    1998-01-01

    Our purpose was to study the effects of corticotropin-releasing factor on (1) maternal blood pressure, (2) uterine vasculature, and (3) parturition in pregnant rats. Infusion minipumps containing vehicle, corticotropin-releasing factor, or alpha-helical corticotropin-releasing factor 9-41 (corticotropin-releasing factor receptor antagonist) were inserted subcutaneously in timed pregnant rats on day 16 of gestation. Systolic blood pressure was measured daily by the tail-cuff method. The time of onset of labor was determined and the newborn pups were weighed. Circulating levels of corticotropin-releasing factor were measured in untreated controls by radioimmunoassay. Relaxant responses to corticotropin-releasing factor were studied in isolated segments of uterine artery from late (day 18) and term (day 22) pregnant rats mounted in a wire myograph. The blood pressure was decreased by corticotropin-releasing factor and increased by alpha-helical corticotropin-releasing factor 9-41 (p < 0.05). The time of onset of labor was not affected by either treatment. Pup weight was decreased by corticotropin-releasing factor (p < 0.05). Circulating levels of corticotropin-releasing factor (immunoreactive) were not changed in pregnancy. In vitro, corticotropin-releasing factor caused relaxation of the uterine artery in a concentration-dependent manner and the relaxation was decreased at term compared with late pregnancy (p < 0.05). Endogenously produced corticotropin-releasing factor lowers blood pressure during pregnancy in rats. It is a relaxant of uterine vasculature and this effect is decreased at term. It does not play an essential role in the initiation of labor in rats.

  5. Activin A, corticotropin-releasing factor and prostaglandin F2 alpha increase immunoreactive oxytocin release from cultured human placental cells.

    PubMed

    Florio, P; Lombardo, M; Gallo, R; Di Carlo, C; Sutton, S; Genazzani, A R; Petraglia, F

    1996-01-01

    The aim of the present study was to investigate the presence of the immunoreactive oxytocin in human placental extracts and putative factors regulating the release of immunoreactive oxytocin from cultured human placental cells. Fresh placental tissue was collected from pregnant women at term and dissected of membranes (n = 5). Presence of immunoreactive oxytocin in trophoblast tissue was evaluated by a specific radio-immunoassay after acidic extraction and high-pressure liquid chromatography. In a second set of experiments, primary cultures of placental cells were performed and, 48-72 h after dissociation, the effect of arginine vasopressin, corticotropin-releasing factor, neuropeptide Y, activin A, inhibin A, noradrenaline or prostaglandins on immunoreactive oxytocin level in culture medium was investigated. The presence of immunoreactive oxytocin was shown in the acidic extract of trophoblast at term, and in the culture medium of human placental cells, and it was identical to the native peptide. The addition of corticotropin-releasing factor or arginine vasopressin, but not of neuropeptide Y, increased the release of immunoreactive oxytocin three- to fourfold from placental cells, with a dose-dependent effect (P < 0.01). A significantly increased release of immunoreactive oxytocin was shown in presence of noradrenaline (P < 0.01), which was reversed by prazosin, an antagonist of alpha-adrenergic receptors. Recombinant human activin A (P < 0.01), but not inhibin A, stimulated the release of immunoreactive oxytocin three- to fourfold from placental cells. Prostaglandin F2 alpha was a potent secretagogue of immunoreactive oxytocin, whereas a partial or no effect was observed when prostaglandin E2 or prostaglandin I2 was added. Thus, the present findings showed that human placenta contains immunoreactive oxytocin, and that its release from cultured placental cells is regulated by neurohormones, growth factors or prostaglandins.

  6. Stress-Derived Corticotropin Releasing Factor Breaches Epithelial Endotoxin Tolerance

    PubMed Central

    Yu, Yong; Geng, Xiao-Rui; Yang, Gui; Liu, Zhi-Gang; Zheng, Peng-Yuan; Yang, Ping-Chang

    2013-01-01

    Background and aims Loss of the endotoxin tolerance of intestinal epithelium contributes to a number of intestinal diseases. The etiology is not clear. Psychological stress is proposed to compromise the intestinal barrier function. The present study aims to elucidate the role of the stress-derived corticotropin releasing factor (CRF) in breaching the established intestinal epithelial endotoxin tolerance. Methods Epithelial cells of HT-29, T84 and MDCK were exposed to lipopolysaccharide to induce the endotoxin tolerance; the cells were then stimulated with CRF. The epithelial barrier function was determined using as indicators of the endotoxin tolerant status. A water-avoid stress mouse model was employed to test the role of CRF in breaching the established endotoxin tolerance in the intestine. Results The established endotoxin tolerance in the epithelial cell monolayers was broken down by a sequent exposure to CRF and LPS manifesting a marked drop of the transepithelial resistance (TER) and an increase in the permeability to a macromolecular tracer, horseradish peroxidase (HRP). The exposure to CRF also increased the expression of Cldn2 in the epithelial cells, which could be mimicked by over expression of TLR4 in epithelial cells. Over expression of Cldn2 resulted in low TER in epithelial monolayers and high permeability to HRP. After treating mice with the 10-day chronic stress, the intestinal epithelial barrier function was markedly compromised, which could be prevented by blocking either CRF, or TLR4, or Cldn2. Conclusions Psychological stress-derived CRF can breach the established endotoxin tolerance in the intestinal mucosa. PMID:23840363

  7. Histamine and mast cell activator compound 48/80 are safe but inefficient systemic adjuvants for gilthead seabream vaccination.

    PubMed

    Gómez González, N E; Cabas, I; Montero, J; García Alcázar, A; Mulero, V; García Ayala, A

    2017-07-01

    Histamine has a key role in the regulation of inflammatory and innate immune responses in vertebrates. Gilthead seabream (Sparus aurata L.), a marine hermaphrodite teleost of great commercial value, was the first fish species shown to possess histamine-containing mast cells (MCs) at mucosal tissues. MCs are highly abundant in the peritoneal exudate of gilthead seabream and compound 48/80 (Co 48/80), often used to promote MC activation and histamine release, is able to promote histamine release from gilthead seabream MCs in vitro and in vivo. The aim of the present study was to analyze the effect of histamine and Co 48/80 on the immune responses of gilthead seabream. For this purpose, histamine and Co 48/80 were intraperitoneally injected alone or combined with 10(9) heat-killed Vibrio anguillarum cells and their effects on head kidney and peritoneal exudate were analyzed. The results indicated that although histamine and Co 48/80 were both able to alter the percentage of peritoneal exudate and head kidney immune cell types, only Co 48/80 increased reactive oxygen species production by peritoneal leukocytes. In addition, histamine, but not Co 48/80, was able to slightly impair the humoral adaptive immune response, i.e. production of specific IgM to V. anguillarum. Notably, both histamine and Co 48/80 reduced the expression of the gene encoding histamine receptor H2 in peritoneal exudate leukocytes. These results show for the first time in fish that although systemic administration of histamine and Co 48/80 is safe, neither compound can be regarded as an efficient adjuvant for gilthead seabream vaccination.

  8. Functional characteristics of histamine receptor-bearing mononuclear cells. I. Selective production of lymphocyte chemoattractant lymphokines with histamine used as a ligand.

    PubMed

    Center, D M; Cruikshank, W W; Berman, J S; Beer, D J

    1983-10-01

    Mitogens and antigens have been the traditional ligands for activating lymphocytes in vitro for the elaboration of lymphokines. Recently, histamine, by interaction with histamine-type 2 receptors on T lymphocytes, has been found to induce the production of one lymphokine, histamine-induced suppressor factor (HSF), that inhibits lymphocyte proliferation and lymphokine production in vitro. Because the biologic effects of HSF appear to be confined to alterations in lymphocyte function, we assessed the ability of soluble products of histamine-stimulated human blood mononuclear cells to affect another lymphocyte function, motility. Utilizing a modified Boyden chamber assay to assess lymphocyte migration, we identified chemoattractant activity for human blood and rat splenic T lymphocytes in histamine-induced mononuclear cell supernatants. No neutrophil or monocyte chemoattractant activity was present. Sephadex G-100 gel filtration of histamine-induced supernatants showed the lymphotactic activity eluted with a 56,000 m.w. This activity was cationic as determined by its elution pattern from a Sephadex QAE anion exchange matrix with a single pl of 9.0 to 9.4 determined by isoelectric focusing in sucrose. Its biologic activity is predominantly chemokinetic in nature, is stable to heating at 56 degrees C for 30 min, but is sensitive to the effects of trypsin and neuraminidase. These physicochemical and functional characteristics establish it as identical to a recently described concanavalin A-induced (Con A) lymphotactic lymphokine (LCF). Mononuclear cells that did not adhere to a histamine affinity matrix were unable to produce LCF when subsequently stimulated with histamine or Con A. Mononuclear cells incubated with histamine and diphenhydramine produced LCF; the addition of cimetidine eliminated LCF production. In fact, supernatants from cells incubated with histamine and cimetidine significantly inhibited lymphocyte migration, a phenomenon explainable by the two regions

  9. Effects of sympathetic histamine on vasomotor responses of blood vessels in rabbit ear to electrical stimulation.

    PubMed

    Chen, Ying-Ying; Lv, Jun; Xue, Xiao-Yan; He, Gong-Hao; Zhou, Ying; Jia, Min; Luo, Xiao-Xing

    2010-06-01

    To investigate the effects of histamine receptor antagonists on vasoconstriction induced by electrical stimulation (ES) on posterior auricular nerve, and to explore the pre- and post-synaptic effects of sympathetic histamine on the vasomotor responses of vascular smooth muscle in rabbit ear. ES was applied to posterior auricular nerves of the whole rabbit ear at 10 Hz, 20 Hz and 40 Hz, respectively. Besides, the whole ear was perfused with different histamine receptor antagonists under constant perfusion pressure, and the changes in the flow rate of perfusate were observed. The flow rate of venous outflow was decreased by ES at all the 3 frequencies. The ES-induced vasoconstriction at 20 Hz and 40 Hz could be partly inhibited by H(1) receptor antagonist chlorpheniramine (P < 0.05). After exhaustion of histamine in mast cells by pretreatment with specific mast cell degranulator compound 48/80, chlorpheniramine could still inhibit the ES-induced flow rate reduction. In contrast, H(2) receptor antagonist cimetidine could enhance the 40-Hz ES-induced flow rate reduction (P < 0.05). Moreover, ES-induced vasoconstriction at the 3 frequencies could all be enhanced by H(3) receptor antagonist thioperamide (P < 0.05). Stimulation on the auricular nerve may evoke histamine release from sympathetic nerves rather than from mast cells. Moreover, the functions of sympathetic histamine vary from pre-synaptic modulation to post-synaptic vasoconstriction or vasodilatation, via activation of different histamine receptors.

  10. Satiety factor oleoylethanolamide recruits the brain histaminergic system to inhibit food intake

    PubMed Central

    Provensi, Gustavo; Coccurello, Roberto; Umehara, Hayato; Munari, Leonardo; Giacovazzo, Giacomo; Galeotti, Nicoletta; Nosi, Daniele; Gaetani, Silvana; Romano, Adele; Moles, Anna; Blandina, Patrizio; Passani, Maria Beatrice

    2014-01-01

    Key factors driving eating behavior are hunger and satiety, which are controlled by a complex interplay of central neurotransmitter systems and peripheral stimuli. The lipid-derived messenger oleoylethanolamide (OEA) is released by enterocytes in response to fat intake and indirectly signals satiety to hypothalamic nuclei. Brain histamine is released during the appetitive phase to provide a high level of arousal in anticipation of feeding, and mediates satiety. However, despite the possible functional overlap of satiety signals, it is not known whether histamine participates in OEA-induced hypophagia. Using different experimental settings and diets, we report that the anorexiant effect of OEA is significantly attenuated in mice deficient in the histamine-synthesizing enzyme histidine decarboxylase (HDC-KO) or acutely depleted of histamine via interocerebroventricular infusion of the HDC blocker α-fluoromethylhistidine (α-FMH). α-FMH abolished OEA-induced early occurrence of satiety onset while increasing histamine release in the CNS with an H3 receptor antagonist-increased hypophagia. OEA augmented histamine release in the cortex of fasted mice within a time window compatible to its anorexic effects. OEA also increased c-Fos expression in the oxytocin neurons of the paraventricular nuclei of WT but not HDC-KO mice. The density of c-Fos immunoreactive neurons in other brain regions that receive histaminergic innervation and participate in the expression of feeding behavior was comparable in OEA-treated WT and HDC-KO mice. Our results demonstrate that OEA requires the integrity of the brain histamine system to fully exert its hypophagic effect and that the oxytocin neuron-rich nuclei are the likely hypothalamic area where brain histamine influences the central effects of OEA. PMID:25049422

  11. Satiety factor oleoylethanolamide recruits the brain histaminergic system to inhibit food intake.

    PubMed

    Provensi, Gustavo; Coccurello, Roberto; Umehara, Hayato; Munari, Leonardo; Giacovazzo, Giacomo; Galeotti, Nicoletta; Nosi, Daniele; Gaetani, Silvana; Romano, Adele; Moles, Anna; Blandina, Patrizio; Passani, Maria Beatrice

    2014-08-05

    Key factors driving eating behavior are hunger and satiety, which are controlled by a complex interplay of central neurotransmitter systems and peripheral stimuli. The lipid-derived messenger oleoylethanolamide (OEA) is released by enterocytes in response to fat intake and indirectly signals satiety to hypothalamic nuclei. Brain histamine is released during the appetitive phase to provide a high level of arousal in anticipation of feeding, and mediates satiety. However, despite the possible functional overlap of satiety signals, it is not known whether histamine participates in OEA-induced hypophagia. Using different experimental settings and diets, we report that the anorexiant effect of OEA is significantly attenuated in mice deficient in the histamine-synthesizing enzyme histidine decarboxylase (HDC-KO) or acutely depleted of histamine via interocerebroventricular infusion of the HDC blocker α-fluoromethylhistidine (α-FMH). α-FMH abolished OEA-induced early occurrence of satiety onset while increasing histamine release in the CNS with an H3 receptor antagonist-increased hypophagia. OEA augmented histamine release in the cortex of fasted mice within a time window compatible to its anorexic effects. OEA also increased c-Fos expression in the oxytocin neurons of the paraventricular nuclei of WT but not HDC-KO mice. The density of c-Fos immunoreactive neurons in other brain regions that receive histaminergic innervation and participate in the expression of feeding behavior was comparable in OEA-treated WT and HDC-KO mice. Our results demonstrate that OEA requires the integrity of the brain histamine system to fully exert its hypophagic effect and that the oxytocin neuron-rich nuclei are the likely hypothalamic area where brain histamine influences the central effects of OEA.

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

    PubMed

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

    2000-02-28

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

  13. Fluorescence-based retention assays reveals sustained release of vascular endothelial growth factor from bone grafts.

    PubMed

    Kang, Wonmo; Yun, Ye-Rang; Lee, Dong-Sung; Kim, Tae-Hyun; Kim, Joong-Hyun; Kim, Hae-Won; Jang, Jun-Hyeog

    2016-01-01

    The sustained release of growth factors following their implantation in vivo is essential for successful outcomes in bone tissue engineering. In this study, we evaluated the release kinetics and delivery efficacies of vascular endothelial growth factor (VEGF), a potent angiogenic growth factor, incorporated into calcium phosphate bone grafts (BGs). We evaluated the release profile of VEGF from BGs using a novel fluorescence-based retention assay, which revealed that VEGF loaded on BGs can be released in a sustained manner without an initial burst (near zero-order cumulative release) with a controlled release rate of 13.6% per week for up to 7 weeks. In contrast, an ELISA-based release assay showed VEGF to have an early burst-release profile for the first week. However, the biological activity of VEGF released from the BGs was preserved over the 7-week release period, which is consistent with the sustained-release profile observed in the fluorescence-based retention assay. Furthermore, the in vivo bone-forming action of the VEGF-loaded BGs was well demonstrated in a rat subcutaneous model. Taken together, the sustained release of VEGF loaded onto BGs was effective in stimulating proliferation, angiogenesis and osteogenesis, suggesting the ultimate value of VEGF-engineered BGs for bone tissue engineering.

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

    PubMed Central

    Kofler, Lukas; Ulmer, Hanno; Kofler, Heinz

    2011-01-01

    Background. Histamine intolerance results from an imbalance between histamine intake and degradation. In healthy persons, dietary histamine can be sufficiently metabolized by amine oxidases, whereas persons with low amine oxidase activity are at risk of histamine toxicity. Diamine oxidase (DAO) is the key enzyme in degradation. Histamine elicits a wide range of effects. Histamine intolerance displays symptoms, such as rhinitis, headache, gastrointestinal symptoms, palpitations, urticaria and pruritus. Objective. Diagnosis of histamine intolerance until now is based on case history; neither a validated questionnaire nor a routine test is available. It was the aim of this trial to evaluate the usefullness of a prick-test for the diagnosis of histamine intolerance. Methods. Prick-testing with 1% histamine solution and wheal size-measurement to assess the relation between the wheal in prick-test, read after 20 to 50 minutes, as sign of slowed histamine degradation as well as history and symptoms of histamine intolerance. Results. Besides a pretest with 17 patients with HIT we investigated 156 persons (81 with HIT, 75 controls): 64 out of 81 with histamine intolerance(HIT), but only 14 out of 75 persons from the control-group presented with a histamine wheal ≥3 mm after 50 minutes (P < .0001). Conclusion and Clinical Relevance. Histamine-50 skin-prickt-test offers a simple tool with relevance. PMID:23724226

  15. Characteristics of histamine-induced leukocyte rolling in the undisturbed microcirculation of the rat mesentery

    PubMed Central

    Yamaki, Kohji; Thorlacius, Henrik; Xie, Xun; Lindbom, Lennart; Hedqvist, Per; Raud, Johan

    1998-01-01

    histamine by 52%, while both H2-receptor antagonists were completely inactive. However, the combination of cimetidine and diphenhydramine reduced the histamine-induced PMNL rolling by 82%. Furthermore, in contrast to an H3-receptor agonist, challenge with either the H1-receptor agonist 2-thiazolylethylamine or two different H2-receptor agonists (impromidine, dimaprit) was sufficient to provoke significant venular PMNL accumulation. Treatment with the nitric oxide-synthase inhibitor L-NAME did not affect the histamine-induced PMNL rolling. On the other hand, 3 h pretreatment with dexamethasone reduced the PMNL response to histamine by 73%, and flow cytometric analysis showed that the dexamethasone treatment almost completely inhibited binding of soluble P-selectin to rat isolated PMNLs. We conclude that initial leukocyte recruitment after mast cell activation in the rat mesentery is critically dependent on histamine release. The cellular response to histamine was specifically due to PMNL rolling, involved activation of both H1- and H2-receptors, and lasted for 2–3 h. Moreover, the histamine-induced PMNL rolling was not dependent on nitric oxide synthesis, but was sensitive to glucocorticoid treatment, possibly via inhibition of expression or function of leukocytic P-selectin ligand(s). PMID:9504378

  16. Stimulation of 14-3-3 protein and its isoform on histamine secretion from permeabilized rat peritoneal mast cells.

    PubMed

    Fujii, Toshihiro; Ueeda, Takayuki

    2002-12-01

    The effect of the 14-3-3 protein, an adaptor protein of intracellular signal pathways, on histamine release from rat peritoneal mast cells was investigated. The exogenous 14-3-3 protein from bovine brain increased the Ca(2+)-dependent histamine release from permeabilized mast cells, but only slightly affected the non-permeabilized cells. Partial amino acid sequences showed that the bovine brain 14-3-3 protein contained 14-3-3beta, gamma and zeta isoforms, and that these recombinant isoforms were prepared. Among them, 14-3-3zeta was an active species while the 14-3-3beta and gamma were inactive for histamine release from the permeabilized mast cells. Approximately 15% of the histamine release was stimulated by 14-3-3zeta at 2.5 microM, and half-maximal stimulation occurred at 1 microM. Treatment of the mast cells with wortmannin or staurosporine completely inhibited the stimulatory effect on histamine release caused by Ca(2+) or Ca(2+)/14-3-3zeta, and genistein partially inhibited both stimulatory effects. PD 98059, however, had little effect on the histamine release. These results suggest the possibility that 14-3-3zeta is associated with signal transduction for degranulation of the mast cells.

  17. Histamine Enhances Voltage-Gated Potassium Currents of ON Bipolar Cells in Macaque Retina

    PubMed Central

    Yu, Yong-Chun; Satoh, Hiromasa; Wu, Samuel M.; Marshak, David W.

    2012-01-01

    Purpose The goal was to understand the functions of retinopetal axons containing histamine. In prior work, type 3 histamine receptors (HR3) have been localized to the tips of ON bipolar cell dendrites in macaque retinas. Voltage-gated potassium channels have also been localized to bipolar cell dendrites, and the hypothesis tested in the present study was that these are modulated by histamine. Methods Whole-cell recordings of potassium currents were made from bipolar cells in slice preparations of macaque retina. In voltage-clamp mode, the cells were held at −60 mV and stepped to values from −60 to 80 mV. Recordings of the membrane potential were also made in current-clamp mode. Histamine, the HR3 agonist (R) α-methylhistamine (RAMH), tetraethyl ammonium (TEA), and 4-aminopyridine (4-AP) were applied in the superfusate. Results Histamine produced a dose-dependent increase in potassium currents in a subset of bipolar cells. At 5 μM, histamine increased the currents by 15% or more in the ON bipolar cells but not in the OFF bipolar cells. RAMH at 5 μM increased the amplitude of the potassium currents in the ON bipolar cells. In 10 mM TEA, potassium currents were reduced in all the bipolar cells, and there was no effect of histamine. Histamine hyperpolarized the resting membrane potential of the ON bipolar cells by 5 mV. Conclusions By enhancing potassium currents in the ON bipolar cells, histamine is expected to reduce the amplitude of the light responses and limit their duration. The hyperpolarization of the resting membrane potential would also reduce neurotransmitter release at their output synapses. PMID:18836167

  18. The effect of indomethacin on the kinetics of histamine, 48/80 and antigen wealing.

    PubMed Central

    Humphreys, F; Shuster, S

    1990-01-01

    1. The kinetics of weal formation and disappearance following intradermal injection of histamine, compound 48/80 and antigen were measured in indomethacin and inert geltreated human forearm skin. 2. Rates of formation went in descending order for histamine, 48/80 and antigen; rate constants of disappearance for equal sized weals were the same for histamine and 48/80 but were much less for antigen. The corresponding half-lives were 77, 73 and 160 min for histamine, 48/80 and antigen weal disappearance respectively. 3. Cyclo-oxygenase inhibition by topical indomethacin had no effect either on the immediate weal and flare responses or on the rates of formation and disappearance of the weals. 4. These findings together with previous studies using H1-receptor antagonists indicate that 48/80 acts by histamine release but that antigen releases both histamine and an additional material or materials which are not related to cyclo-oxygenase activity. 5. Exacerbation of chronic idiopathic urticaria by cyclo-oxygenase inhibitors is therefore likely to be part of the urticarial disease process. PMID:2106336

  19. Effect of inhaled ozone on lung histamine in conscious guinea pigs

    SciTech Connect

    Shields, R.L.; Gold, W.M.

    1987-04-01

    The effect of short-term ozone (O/sub 3/) exposure on pulmonary mast cell function was examined. Guinea pigs were continuously exposed to 1.0 ppm O/sub 3/ for 2, 4, and 8 hr. O/sub 3/ exposure produced a significant decrease in lung histamine concentration. Two-hour exposure to O/sub 3/ caused a 22.4 +/- 7.0% decrease in lung histamine concentration compared with controls. Ozone exposures of 4 and 8 hr caused lung histamine concentrations to decrease by 43.7 +/- 7.7 and 49.0 +/- 7.5%, respectively, without significant changes in lung water or protein, or evidence of cytotoxicity. These results suggest that O/sub 3/ or its metabolites affect pulmonary mast cell function by stimulating the release of histamine from the lung.

  20. 76 FR 68183 - Highlights of the Exposure Factors Handbook: 2011 Update Release of Final Report

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-03

    ... Exposure Factors Handbook: 2011 Update Release of Final Report AGENCY: Environmental Protection Agency (EPA... Exposure Factors Handbook: 2011 Update. The Highlights of the Exposure Factors Handbook: 2011 Update provides a summary of the recommended exposure factors extracted from the Exposure Factors Handbook...

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

    PubMed

    Detzner, M; Kathmann, M; Schlicker, E

    1994-06-01

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

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

    PubMed

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

    2016-02-01

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

  3. Growth-Factor Nanocapsules That Enable Tunable Controlled Release for Bone Regeneration.

    PubMed

    Tian, Haijun; Du, Juanjuan; Wen, Jing; Liu, Yang; Montgomery, Scott R; Scott, Trevor P; Aghdasi, Bayan; Xiong, Chengjie; Suzuki, Akinobu; Hayashi, Tetsuo; Ruangchainikom, Monchai; Phan, Kevin; Weintraub, Gil; Raed, Alobaidaan; Murray, Samuel S; Daubs, Michael D; Yang, Xianjin; Yuan, Xu-Bo; Wang, Jeffrey C; Lu, Yunfeng

    2016-08-23

    Growth factors are of great potential in regenerative medicine. However, their clinical applications are largely limited by the short in vivo half-lives and the narrow therapeutic window. Thus, a robust controlled release system remains an unmet medical need for growth-factor-based therapies. In this research, a nanoscale controlled release system (degradable protein nanocapsule) is established via in situ polymerization on growth factor. The release rate can be finely tuned by engineering the surface polymer composition. Improved therapeutic outcomes can be achieved with growth factor nanocapsules, as illustrated in spinal cord fusion mediated by bone morphogenetic protein-2 nanocapsules.

  4. Epidermal growth factor acts as a corticotropin-releasing factor in chronically catheterized fetal lambs.

    PubMed Central

    Polk, D H; Ervin, M G; Padbury, J F; Lam, R W; Reviczky, A L; Fisher, D A

    1987-01-01

    Epidermal growth factor (EGF) has been reported to stimulate adrenocorticotropin hormone (ACTH), growth hormone and prolactin secretion from pituitary tissue in vitro, and in large doses evokes ACTH secretion in adult sheep in vivo. In order to assess a possible role for EGF in the pituitary hyperfunction characteristic of the in utero fetus, we measured changes in plasma immunoreactive ACTH concentrations after acute administration of saline, purified mouse EGF or synthetic ovine corticotropin releasing factor (CRF) to chronically catheterized fetal sheep. Both CRF and EGF were associated with increases in plasma immunoreactive ACTH concentrations. Peak values 60 min after 10-micrograms injections of either EGF or CRF increased from baseline ACTH values of 61 +/- 11 pg/ml to 191 +/- 37 and 178 +/- 25 pg/ml, respectively. Dose-response studies indicate that at low doses (less than 20 micrograms) EGF is as potent a stimulus for ACTH release as CRF. EGF infusion was not associated with detectable changes in circulating CRF, catecholamines, arginine vasopressin levels, or plasma growth hormone concentrations. We speculate that EGF may be important in the regulation of pituitary function in the developing mammalian fetus. PMID:3029180

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

    PubMed

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

    2015-10-21

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

  6. Effects of histamine on monocyte complement production. I. Inhibition of C2 production mediated by its action on H2 receptors.

    PubMed

    Lappin, D; Whaley, K

    1980-09-01

    Histamine produced dose-dependent inhibition of the production of the second complement component (C2) by monocytes in tissue culture. The effect was not associated with either cell death, as ascertained by trypan blue exclusion, or loss of cells from the monolayer, as determined by measuring their DNA content. The specificity of the response was shown by the failure of histidine or histamine metabolites to inhibit C2 production. Preincubation of histamine with histaminase also abrogated the histamine effect. The kinetics of the effect were extremely rapid and irreversible, most of the reduction being achieved during a 5-min exposure to histamine. The H2 receptor antagonist cimetidine was able to prevent the histamine response, whereas chlorpheniramine, the H1 receptor antagonist, had no effect. Dimaprit and 4-methyl histamine, H2 receptor agonists, simulated the effect of histamine whereas the H1 receptor agonist 2-(2-aminoethylthiazole) was ineffective, confirming that the effect of histamine on C2 production by monocytes is mediated by the H2 receptors. Thus histamine, released from basophils or mast cells by the C3 and C5 cleavage products C3a and C5a respectively, may exert a negative feedback on further C3 and C5 cleavage by limiting the formation of the C3 (C42) and C5 (C423b) convertases.

  7. [RESEARCH PROGRESS OF CONTROLLED RELEASING DELIVERY OF BIOLOGICAL FACTORS FOR CARTILAGE REPAIR].

    PubMed

    Chen, Jialei; Xiang, Zhou

    2015-08-01

    To summarize the recent progress of the controlled releasing delivery of biological factors for cartilage repair. The recently published literature at home and abroad on the controlled releasing delivery of biological factors for cartilage repair was reviewed and summarized. Various biological factors have been applied for repairing cartilage. For better cartilage repair effects, controlled releasing delivery of biological factors can be applied by means of combining biological factors with degradable biomaterials, or by micro- and nano-particles. Meanwhile, multiple biologic delivery and temporally controlled delivery are also inevitable choices. Although lots of unsolved problems exist, the controlled releasing delivery of biological factors has been a research focus for cartilage repair because of the controllability and delicacy.

  8. Research Advances in Tissue Engineering Materials for Sustained Release of Growth Factors

    PubMed Central

    Zhao, Hai-yang; Wu, Jiang; Zhu, Jing-jing; Xiao, Ze-cong; He, Chao-chao; Shi, Hong-xue; Li, Xiao-kun; Yang, Shu-lin; Xiao, Jian

    2015-01-01

    Growth factors are a class of cytokines that stimulate cell growth and are widely used in clinical practice, such as wound healing, revascularization, bone repair, and nervous system disease. However, free growth factors have a short half-life and are instable in vivo. Therefore, the search of excellent carriers to enhance sustained release of growth factors in vivo has become an area of intense research interest. The development of controlled-release systems that protect the recombinant growth factors from enzymatic degradation and provide sustained delivery at the injury site during healing should enhance the growth factor's application in tissue regeneration. Thus, this study reviews current research on commonly used carriers for sustained release of growth factors and their sustained release effects for preservation of their bioactivity and their accomplishment in tissue engineering approaches. PMID:26347885

  9. Research Advances in Tissue Engineering Materials for Sustained Release of Growth Factors.

    PubMed

    Zhao, Hai-yang; Wu, Jiang; Zhu, Jing-jing; Xiao, Ze-cong; He, Chao-chao; Shi, Hong-xue; Li, Xiao-kun; Yang, Shu-lin; Xiao, Jian

    2015-01-01

    Growth factors are a class of cytokines that stimulate cell growth and are widely used in clinical practice, such as wound healing, revascularization, bone repair, and nervous system disease. However, free growth factors have a short half-life and are instable in vivo. Therefore, the search of excellent carriers to enhance sustained release of growth factors in vivo has become an area of intense research interest. The development of controlled-release systems that protect the recombinant growth factors from enzymatic degradation and provide sustained delivery at the injury site during healing should enhance the growth factor's application in tissue regeneration. Thus, this study reviews current research on commonly used carriers for sustained release of growth factors and their sustained release effects for preservation of their bioactivity and their accomplishment in tissue engineering approaches.

  10. The other side of the histamine H3 receptor.

    PubMed

    Ellenbroek, Bart A; Ghiabi, Bibinaz

    2014-04-01

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

  11. Risk factors for hazardous substance releases that result in injuries and evacuations: data from 9 states.

    PubMed Central

    Hall, H I; Haugh, G S; Price-Green, P A; Dhara, V R; Kaye, W E

    1996-01-01

    This study was undertaken to determine risk factors associated with hazardous substance releases (at fixed facilities or during transport) that have public health consequences. Data from nine states with surveillance systems for such releases and their consequences were analyzed. Risk factors were determined for releases resulting in (1) injuries or (2) evacuations. Both outcomes were more likely to occur as a result of facility releases (odds ratio [OR] = 1.89, 95% confidence interval [CI] = 1.44, 2.47, for injuries; OR = 3.29, 95% CI = 2.28, 4.74, for evacuations). Releases of ammonia, chlorine, and acids resulted in injuries and evacuations more frequently than releases of other substances. PMID:8659662

  12. Release-modulating factors strongly affecting steroid diffusion from silicone elastomer.

    PubMed

    Nash, Harold A; Robertson, Dale N; Evans, Simone J

    2004-10-01

    Investigations were undertaken to determine the cause of decreases over time in the release rate from levonorgestrel (LNG) implants consisting of silicone elastomer tubing filled with crystalline steroid. Emptying and refilling with the same steroid partially restored release rate. Surprisingly, a further increment in release rates was attained if the tubing was briefly irrigated with methanol before refill. Fractional crystallization showed that release-modulating factors could be concentrated in mother liquors and were initially present as impurities. Boiling LNG in ethanol or methanol produced a number of release-modulating factors of which the most prominent was also found in one production lot of LNG. It was identified as 6beta-hydroxy-levonorgestrel (6beta-OH-LNG). Added to LNG at the 2% level, 6beta-OH-LNG decreased the release rate by 27%. Copyright 2004 Wiley-Liss, Inc. and the American Pharmacists Association

  13. Effects of Olopatadine Hydrochloride, a Histamine H1 Receptor Antagonist, on Histamine-Induced Skin Responses

    PubMed Central

    Hashimoto, Takashi; Ishii, Norito; Hamada, Takahiro; Dainichi, Teruki; Karashima, Tadashi; Nakama, Takekuni; Yasumoto, Shinichiro

    2010-01-01

    Effects of olopatadine hydrochloride, a histamine H1 receptor antagonist, on histamine-induced skin responses were evaluated in 10 healthy subjects in comparison with placebo, fexofenadine hydrochloride, and bepotastine besilate. Olopatadine significantly suppressed histamine-induced wheal, flare, and itch, starting 30 minutes after oral administration. Olopatadine was more effective than fexofenadine and bepotastine. None of the drugs studied impaired performance of word processing tasks. These results suggest that olopatadine can suppress skin symptoms caused by histamine soon after administration. PMID:20886023

  14. Effects of olopatadine hydrochloride, a histamine h(1) receptor antagonist, on histamine-induced skin responses.

    PubMed

    Hashimoto, Takashi; Ishii, Norito; Hamada, Takahiro; Dainichi, Teruki; Karashima, Tadashi; Nakama, Takekuni; Yasumoto, Shinichiro

    2010-01-01

    Effects of olopatadine hydrochloride, a histamine H(1) receptor antagonist, on histamine-induced skin responses were evaluated in 10 healthy subjects in comparison with placebo, fexofenadine hydrochloride, and bepotastine besilate. Olopatadine significantly suppressed histamine-induced wheal, flare, and itch, starting 30 minutes after oral administration. Olopatadine was more effective than fexofenadine and bepotastine. None of the drugs studied impaired performance of word processing tasks. These results suggest that olopatadine can suppress skin symptoms caused by histamine soon after administration.

  15. Histamine and Tyramine in Food.

    DTIC Science & Technology

    1985-05-01

    F. Niven, and G. D. Wilson. 1961. Microbiology of Meat Curing. III. Some microbiological and related technological aspects in the manufacture of...and 0.42 ug/g (1). In yogurt the tyramine concentration was less than 0.2 ug/ml (2). Since the concentrations of tyramine and histamine in these...and not by lactobacilli, added for cheese manufacture , which are anaerobes or facultative anaerobes. The tyramine content of cheese is known to be

  16. Draft Genome Sequences of Histamine- and Non-Histamine-Producing Photobacterium Strains.

    PubMed

    Bjornsdottir-Butler, Kristin; Sanchez Leon, Maria; Dunlap, Paul V; Benner, Ronald A

    2016-09-22

    Histamine-producing bacteria (HPBs) have recently been identified from the marine environment. The identification and characterization of HPBs is important to developing effective mitigation strategies for scombrotoxin fish poisoning. We report here the draft genomes of seven histamine-producing and two non-histamine-producing marine Photobacterium strains. Copyright © 2016 Bjornsdottir-Butler et al.

  17. Draft Genome Sequences of Histamine- and Non-Histamine-Producing Photobacterium Strains

    PubMed Central

    Sanchez Leon, Maria; Dunlap, Paul V.; Benner, Ronald A.

    2016-01-01

    Histamine-producing bacteria (HPBs) have recently been identified from the marine environment. The identification and characterization of HPBs is important to developing effective mitigation strategies for scombrotoxin fish poisoning. We report here the draft genomes of seven histamine-producing and two non-histamine-producing marine Photobacterium strains. PMID:27660786

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

    PubMed

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

    2001-12-01

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

  19. FACTORS RELATING TO THE RELEASE OF STACHYBOTRYS CHARTARUM SPORES FROM CONTAMINATED SOURCES

    EPA Science Inventory

    The paper describes preliminary results of a research project to determine the factors that control the release of S. chartarum spores from a contaminated source and test ways to reduce spore release and thus exposure. As anticipated, S. chartarum spore emissions from gypsum boar...

  20. FACTORS RELATING TO THE RELEASE OF STACHYBOTRYS CHARTARUM SPORES FROM CONTAMINATED SOURCES

    EPA Science Inventory

    The paper describes preliminary results of a research project to determine the factors that control the release of S. chartarum spores from a contaminated source and test ways to reduce spore release and thus exposure. As anticipated, S. chartarum spore emissions from gypsum boar...

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

    PubMed

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

    2015-12-01

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

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

    PubMed

    Koss, M C; Hey, J A

    1993-08-01

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

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

    PubMed Central

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

    2015-01-01

    Histamine is an important chemical messenger that regulates multiple physiological processes in both vertebrate and invertebrate animals. Even so, how glial cells and neurons recycle histamine remains to be elucidated. Drosophila photoreceptor neurons use histamine as a neurotransmitter, and the released histamine is recycled through neighboring glia, where it is conjugated to β-alanine to form carcinine. However, how carcinine is then returned to the photoreceptor remains unclear. In an mRNA-seq screen for photoreceptor cell-enriched transporters, we identified CG9317, an SLC22 transporter family protein, and named it CarT (Carcinine Transporter). S2 cells that express CarT are able to take up carcinine in vitro. In the compound eye, CarT is exclusively localized to photoreceptor terminals. Null mutations of cart alter the content of histamine and its metabolites. Moreover, null cart mutants are defective in photoreceptor synaptic transmission and lack phototaxis. These findings reveal that CarT is required for histamine recycling at histaminergic photoreceptors and provide evidence for a CarT-dependent neurotransmitter trafficking pathway between glial cells and photoreceptor terminals. PMID:26713872

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

    PubMed

    Lacour, M; Sterkers, O

    2001-01-01

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

  5. Platelet-aggregating activity of released factor(s) from Trypanosoma brucei brucei.

    PubMed

    Nwagwu, M; Inyang, A L; Molokwu, R I; Essien, E M

    1989-12-01

    The effect of factors derived from Trypanosoma brucei brucei on rat platelets was studied. T. brucei at a concentration of 4 X 10(9) trypanosomes/ml phosphate saline glucose (PSG) was stored at -20 degrees C for 18 h, thawed, and a supernatant fraction, trypanosome-derived supernatant (TDS) was obtained by spinning the sample at 3000 g for 10 min at 20 degrees C. Normal rat platelets, prepared as platelet-rich plasma (PRP), were then incubated with TDS in the absence or presence of ADP (0.05-0.1 microM). The results showed that approximately 83% platelet aggregation was induced by addition of TDS (50 microliters; 113 micrograms protein) to 100 microliters PRP with a platelet count of 10(6). simultaneous addition of ADP and TDS to PRP produced a synergistic effect. It was also shown that a supernatant fraction, obtained by incubating live T. brucei (4 X 10(9)/microliters PSG) at 0 degrees C 1 h and spinning down the trypanosomes (3000 g for 10 min), also induced platelet aggregation. The nature of the factor(s) derived from, or released by, T. brucei inducing platelet aggregation is being investigated but it has been shown not to be ADP.

  6. Growth factor delivery: How surface interactions modulate release in vitro and in vivo

    PubMed Central

    King, William J.; Krebsbach, Paul H.

    2013-01-01

    Biomaterial scaffolds have been extensively used to deliver growth factors to induce new bone formation. The pharmacokinetics of growth factor delivery has been a critical regulator of their clinical success. This review will focus on the surface interactions that control the non-covalent incorporation of growth factors into scaffolds and the mechanisms that control growth factor release from clinically relevant biomaterials. We will focus on the delivery of recombinant human bone morphogenetic protein-2 from materials currently used in the clinical practice, but also suggest how general mechanisms that control growth factor incorporation and release delineated with this growth factor could extend to other systems. A better understanding of the changing mechanisms that control growth factor release during the different stages of preclinical development could instruct the development of future scaffolds for currently untreatable injuries and diseases. PMID:22433783

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

    PubMed Central

    Rosic, Mirko; Parodi, Oberdan; Jokovic, Vuk; Pantovic, Suzana

    2014-01-01

    We estimated the influence of acute glucagon applications on 3H-histamine uptake by the isolated guinea-pig heart, during a single 3H-histamine passage through the coronary circulation, before and during anaphylaxis, and the influence of glucagon on level of histamine, NO, O2 −, and H2O2 in the venous effluent during anaphylaxis. Before anaphylaxis, glucagon pretreatment does not change 3H-histamine Umax and the level of endogenous histamine. At the same time, in the presence of glucagon, 3H-histamine Unet is increased and backflux is decreased when compared to the corresponding values in the absence of glucagon. During anaphylaxis, in the presence of glucagon, the values of 3H-histamine Umax and Unet are significantly higher and backflux is significantly lower in the presence of glucagon when compared to the corresponding values in the absence of glucagon. The level of endogenous histamine during anaphylaxis in the presence of glucagon (6.9–7.38 × 10−8  μM) is significantly lower than the histamine level in the absence of glucagon (10.35–10.45 × 10−8  μM). Glucagon pretreatment leads to a significant increase in NO release (5.69 nmol/mL) in comparison with the period before glucagon administration (2.49 nmol/mL). Then, in the presence of glucagon, O2 − level fails to increase during anaphylaxis. Also, our results show no significant differences in H2O2 levels before, during, and after anaphylaxis in the presence of glucagon, but these values are significantly lower than the corresponding values in the absence of glucagon. In conclusion, our results show that glucagon increases NO release and prevents the increased release of free radicals during anaphylaxis, and decreases histamine level in the venous effluent during cardiac anaphylaxis, which may be a consequence of decreased histamine release and/or intensified histamine capturing by the heart during anaphylaxis. PMID:24895609

  8. Histamine chloramine reactivity with thiol compounds, ascorbate, and methionine and with intracellular glutathione.

    PubMed

    Peskin, Alexander V; Winterbourn, Christine C

    2003-11-15

    Histamine is stored in granules of mast cells and basophils and released by inflammatory mediators. It has the potential to intercept some of the HOCl generated by the neutrophil enzyme, myeloperoxidase, to produce histamine chloramine. We have measured rate constants for reactions of histamine chloramine with methionine, ascorbate, and GSH at pH 7.4, of 91 M(-1)s(-1), 195 M(-1)s(-1), and 721 M(-1)s(-1), respectively. With low molecular weight thiols, the reaction was with the thiolate and rates increased exponentially with decreasing thiol group pK(a). Comparing rate constants for different chloramines reacting with ascorbate or a particular thiol anion, these were higher when there was less negative charge in the vicinity of the chloramine group. Histamine chloramine was the most reactive among biologically relevant chloramines. Consumption of histamine chloramine and oxidation of intracellular GSH were examined for human fibroblasts. At nontoxic doses, GSH loss over 10 min was slightly greater than that with HOCl, but the cellular uptake of histamine chloramine was 5-10-fold less. With histamine chloramine, GSSG was a minor product and most of the GSH was converted to mixed disulfides with proteins. HOCl gave a different profile of GSH oxidation products, with significantly less GSSG and mixed disulfide formation. There was irreversible oxidation and losses to the medium, as observed with HOCl and other cell types. Thus, histamine chloramine shows high preference for thiols both in isolation and in cells, and in this respect is more selective than HOCl.

  9. The behavioral and biochemical effects of thioperamide, a histamine H3-receptor antagonist, in a light/dark test measuring anxiety in mice.

    PubMed

    Imaizumi, M; Onodera, K

    1993-01-01

    We investigated the effects of thioperamide, a histamine H3-receptor antagonist, in a light/dark test measuring anxiety in mice. Thioperamide (20 mg/kg) slightly affected the locomotion and time spent in a light zone, and shuttle crossing. However, the decreases of these parameters were significant only when the animals were pretreated with zolantidine, a histamine H2-receptor antagonist. Moreover, the decreased parameters induced by the combination of thioperamide and zolantidine were reversed by pretreatment with pyrilamine, a histamine H1-receptor antagonist. These data suggest that thioperamide induces the release of neuronal histamine, which in turn stimulates both H1- and H2-receptors to produce the anxiogenic effect. The stimulation of histamine H1-receptors may mediate the anxiety, while H2-receptors may play a role in masking the anxiogenic effect. Thus, the present study suggests the involvement of endogenous neuronal brain histamine in anxiety. In the biochemical study, a previous report showed that thioperamide accelerated the release of neuronal histamine in the brains of mice [Sakai et al., Life Sciences, 48, 2397-2404(1991)]. This study also demonstrated that thioperamide did not affect the turnover rate of noradrenaline, dopamine, or serotonin in the brains of mice, which indicates that thioperamide is a good pharmacological tool for accelerating the release of neuronal histamine in the brain.

  10. Enhancement of RNA Polymerase Activity by a Factor Released by Auxin from Plasma Membrane*

    PubMed Central

    Hardin, James W.; Cherry, Joe H.; Morré, D. James; Lembi, Carole A.

    1972-01-01

    Using recently developed techniques for solubilization of RNA polymerase from soybean chromatin and isolation of plasma membrane fractions from plants we can show the presence of a transcriptional factor specifically released from the membranes by auxin, 2,4-dichlorophenoxyacetic acid. The nonauxin, 3,5-dichlorophenoxyacetic acid, does not release the factor, but subsequent exposure of the membranes to auxin results in its release. Factor activity could not be demonstrated in fractions devoid of plasma membranes. The presence of a regulatory factor for RNA polymerase associated with plant plasma membrane and specifically released by auxin provides a mechanism whereby both rapid growth responses and delayed nuclear changes could be derived from a common auxin receptor site associated with plasma membrane. Images PMID:4508307

  11. Controllable mineral coatings on scaffolds as carriers for growth factor release for bone tissue engineering

    NASA Astrophysics Data System (ADS)

    Saurez-Gonzalez, Darilis

    The work presented in this document, focused on the development and characterization of mineral coatings on scaffold materials to serve as templates for growth factor binding and release. Mineral coatings were formed using a biomimetic approach that consisted in the incubation of scaffolds in modified simulated body fluids (mSBF). To modulate the properties of the mineral coating, which we hypothesized would dictate growth factor release, we used carbonate (HCO3) concentration in mSBF of 4.2 mM, 25mM, and 100mM. Analysis of the mineral coatings formed using scanning electron microscopy indicated growth of a continuous layer of mineral with different morphologies. X-ray diffraction analysis showed peaks associated with hydroxyapatite. FTIR data confirmed the substitution of HCO3 in the mineral. As the extent of HCO3 substitution increased, the coating exhibited more rapid dissolution kinetics in an environment deficient in calcium and phosphate. The mineral coatings provided an effective mechanism for bioactive growth factor binding and release. Peptide versions of vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP2) were bound with efficiencies up to 90% to mineral-coated PCL scaffolds. Recombinant human vascular endothelial growth factor (rhVEGF) also bound to mineral coated scaffolds with lower efficiency (20%) and released with faster release kinetics compared to peptides growth factor. Released rhVEGF induced human umbilical vein endothelial cell (HUVEC) proliferation in vitro and enhanced blood vessel formation in vivo in an intramuscular sheep model. In addition to the use the mineral coatings for single growth factor release, we expanded the concept and bound both an angiogenic (rhVEGF) and osteogenic (mBMP2) growth factor by a simple double dipping process. Sustained release of both growth factors was demonstrated for over 60 days. Released rhVEGF enhanced blood vessel formation in vivo in sheep and its biological activity was

  12. Comparative release of growth factors from PRP, PRF, and advanced-PRF.

    PubMed

    Kobayashi, Eizaburo; Flückiger, Laura; Fujioka-Kobayashi, Masako; Sawada, Kosaku; Sculean, Anton; Schaller, Benoit; Miron, Richard J

    2016-12-01

    The use of platelet concentrates has gained increasing awareness in recent years for regenerative procedures in modern dentistry. The aim of the present study was to compare growth factor release over time from platelet-rich plasma (PRP), platelet-rich fibrin (PRF), and a modernized protocol for PRF, advanced-PRF (A-PRF). Eighteen blood samples were collected from six donors (3 samples each for PRP, PRF, and A-PRF). Following preparation, samples were incubated in a plate shaker and assessed for growth factor release at 15 min, 60 min, 8 h, 1 day, 3 days, and 10 days. Thereafter, growth factor release of PDGF-AA, PDGF-AB, PDGF-BB, TGFB1, VEGF, EGF, and IGF was quantified using ELISA. The highest reported growth factor released from platelet concentrates was PDGF-AA followed by PDGF-BB, TGFB1, VEGF, and PDGF-AB. In general, following 15-60 min incubation, PRP released significantly higher growth factors when compared to PRF and A-PRF. At later time points up to 10 days, it was routinely found that A-PRF released the highest total growth factors. Furthermore, A-PRF released significantly higher total protein accumulated over a 10-day period when compared to PRP or PRF. The results from the present study indicate that the various platelet concentrates have quite different release kinetics. The advantage of PRP is the release of significantly higher proteins at earlier time points whereas PRF displayed a continual and steady release of growth factors over a 10-day period. Furthermore, in general, it was observed that the new formulation of PRF (A-PRF) released significantly higher total quantities of growth factors when compared to traditional PRF. Based on these findings, PRP can be recommended for fast delivery of growth factors whereas A-PRF is better-suited for long-term release.

  13. Protective Factors for Violence among Released Prisoners--Effects over Time and Interactions with Static Risk

    ERIC Educational Resources Information Center

    Ullrich, Simone; Coid, Jeremy

    2011-01-01

    Objective: There is a substantial body of research on risk factors for violent behavior in adulthood but little empirical study of protective factors and desistance. Method: This study aimed to investigate the protective effects of factors hypothesized to reduce violent reoffending among a sample of 800 male prisoners following release into the…

  14. Protective Factors for Violence among Released Prisoners--Effects over Time and Interactions with Static Risk

    ERIC Educational Resources Information Center

    Ullrich, Simone; Coid, Jeremy

    2011-01-01

    Objective: There is a substantial body of research on risk factors for violent behavior in adulthood but little empirical study of protective factors and desistance. Method: This study aimed to investigate the protective effects of factors hypothesized to reduce violent reoffending among a sample of 800 male prisoners following release into the…

  15. Insulin-like growth factor I modulates hypothalamic somatostatin through a growth hormone releasing factor increased somatostatin release and messenger ribonucleic acid levels.

    PubMed

    Aguila, M C; Boggaram, V; McCann, S M

    1993-10-22

    Insulin-like growth factor I (IGF-I) has been shown to participate in feedback inhibition of growth hormone (GH) secretion at the level of both the pituitary and hypothalamus. Therefore, we tested the possible involvement of IGF-I on somatostatin (SRIF) and GH-releasing factor (GRF) release in median eminence (ME) fragments and periventricular nucleus (PeN) of male rats. The levels of SRIF messenger ribonucleic acid (mRNA) were also determined in PeN incubated in vitro with IGF-I. The ME's were incubated in Krebs-Ringer bicarbonate glucose buffer in the presence of various concentrations of IGF-I (10(-7) to 10(-11) M) for 30 min. SRIF and GRF released into the medium were quantitated by RIA. The release of SRIF and GRF from the ME's was stimulated significantly (P < 0.025 and P < 0.05, respectively) by 10(-9) M IGF-I. To determine whether the effect of IGF-I on SRIF release is mediated by GRF release in the ME, a specific GRF antibody (ab) (1:500) was used concomitantly with IGF-I (10(-9) M). The release of SRIF induced by IGF-I was blocked by the GRF ab (P < 0.001), but not by normal rabbit serum used at the same dilution. To determine the effect of IGF-I on the regulation of SRIF mRNA levels, SRIF mRNA was determined in PeN explants incubated in the presence of IGF-I (10(-8) to 10(-10) M) for 2 to 6 h. Levels of SRIF mRNA were determined by a S1 nuclease protection assay using a 32P-labelled rat SRIF riboprobe.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Absorption and catabolism of histamine in sheep

    PubMed Central

    Kay, R. N. B.; Sjaastad, Ø. V.

    1974-01-01

    1. The fate of dietary histamine in sheep has been studied. When 200 mg histamine diphosphate was administered into a rumen with normal contents the average time taken for the biological activity to disappear from the rumen was about 4 hr. In sheep starved for 60 hr the activity disappeared much more slowly. 2. When 0·9% NaCl solution was substituted for the normal rumen contents and the rumen was isolated in situ under anaesthesia, the disappearance of histamine was scarcely detectable. About 1% of the radioactivity introduced into such rumen preparations as [14C]histamine was recovered in the urine during a 6 hr period. 3. When both [14C]histamine and 200 mg unlabelled histamine diphosphate were administered into the rumen, between 4 and 15% of the radioactivity and 2 and 11% of the biological activity reached the duodenum. 4. When jejunal loops isolated between two pairs of re-entrant cannulas were perfused with 0·9% NaCl solution containing histamine a considerable fraction of the histamine was absorbed from the loops. 5. When [14C]histamine and 200 mg histamine diphosphate were administered into the rumen an average of 9% of the radioactivity appeared in the urine. When histamine was given into the abomasum the corresponding figure in a single experiment was 25%. 6. Between 11 and 34% of the radioactivity administered into the rumen as [14C]histamine was exhaled as 14CO2. Most of the 14CO2 seemed to stem from metabolism of [14C]histamine in the ruminoreticulum whereas the contribution of the intestines to 14CO2 was very small. 7. When [3H]histamine was administered into the rumen most of the radioactivity in the urine a few days after administration was in the form of tritiated water. The formation of 3H2O is probably a result of histamine metabolism in the fore-stomach, analogous to the formation of 14CO2. PMID:4449065

  17. Factors affecting ferulic acid release from Brewer's spent grain by Fusarium oxysporum enzymatic system.

    PubMed

    Xiros, Charilaos; Moukouli, Maria; Topakas, Evangelos; Christakopoulos, Paul

    2009-12-01

    In this study, the factors affecting ferulic acid (FA) release from Brewer's spent grain (BSG), by the crude enzyme extract of Fusarium oxysporum were investigated. In order to evaluate the importance of the multienzyme preparation on FA release, the synergistic action of feruloyl esterase (FAE, FoFaeC-12213) and xylanase (Trichoderma longibrachiatum M3) monoenzymes was studied. More than double amount of FA release (1 mg g(-1) dry BSG) was observed during hydrolytic reactions by the crude enzyme extract compared to hydrolysis by the monoenzymes (0.37 mg g(-1) dry BSG). The protease content of the crude extract and the inhibitory effect of FA as an end-product were also evaluated concerning their effect on FA release. The protease treatment prior to hydrolysis by monoenzymes enhanced FA release about 100%, while, for the first time in literature, FA in solution found to have a significant inhibitory effect on FAE activity and on total FA release.

  18. Effect of Cellulose Acetate Beads on the Release of Transforming Growth Factor-β.

    PubMed

    Nishise, Shoichi; Abe, Yasuhiko; Nomura, Eiki; Sato, Takeshi; Sasaki, Yu; Iwano, Daisuke; Yagi, Makoto; Sakuta, Kazuhiro; Shibuya, Rika; Mizumoto, Naoko; Kanno, Nana; Ueno, Yoshiyuki

    2015-08-01

    Transforming growth factor-β (TGF-β) is released by activated platelets and induces the differentiation of T-helper 17 from naïve T cells. Contact between blood and cellulose acetate (CA) beads induces cytokine release, although their inflammatory effects on TGF-β release are unclear. We aimed to clarify the effect of CA beads on the release of TGF-β in vitro. We incubated peripheral blood with and without CA beads and measured platelets and TGF-β. Compared with blood samples incubated without beads, the platelet count and amount of TGF-β significantly decreased in blood samples incubated with CA beads. In conclusion, CA beads inhibited the release of TGF-β from adsorbed platelets. The biological effects of this reduction of TGF-β release during platelet adsorption to CA beads need further clarification.

  19. Frontline Science: Corticotropin-releasing factor receptor subtype 1 is a critical modulator of mast cell degranulation and stress-induced pathophysiology.

    PubMed

    Ayyadurai, Saravanan; Gibson, Amelia J; D'Costa, Susan; Overman, Elizabeth L; Sommerville, Laura J; Poopal, Ashwini C; Mackey, Emily; Li, Yihang; Moeser, Adam J

    2017-07-06

    Life stress is a major risk factor in the onset and exacerbation of mast cell-associated diseases, including allergy/anaphylaxis, asthma, and irritable bowel syndrome. Although it is known that mast cells are highly activated upon stressful events, the mechanisms by which stress modulates mast cell function and disease pathophysiology remains poorly understood. Here, we investigated the role of corticotropin-releasing factor receptor subtype 1 (CRF1) in mast cell degranulation and associated disease pathophysiology. In a mast cell-dependent model of IgE-mediated passive systemic anaphylaxis (PSA), prophylactic administration of the CRF1-antagonist antalarmin attenuated mast cell degranulation and hypothermia. Mast cell-deficient Kit(W-sh/W-sh) mice engrafted with CRF1(-/-) bone marrow-derived mast cells (BMMCs) exhibited attenuated PSA-induced serum histamine, hypothermia, and clinical scores compared with wild-type BMMC-engrafted Kit(W-sh/W-sh) mice. Kit(W-sh/W-sh) mice engrafted with CRF1(-/-) BMMCs also exhibited suppressed in vivo mast cell degranulation and intestinal permeability in response to acute restraint stress. Genetic and pharmacologic experiments with murine BMMCs, rat RBL-2H3, and human LAD2 mast cells demonstrated that although CRF1 activation did not directly induce MC degranulation, CRF1 signaling potentiated the degranulation responses triggered by diverse mast cell stimuli and was associated with enhanced release of Ca(2+) from intracellular stores. Taken together, our results revealed a prominent role for CRF1 signaling in mast cells as a positive modulator of stimuli-induced degranulation and in vivo pathophysiologic responses to immunologic and psychologic stress. © Society for Leukocyte Biology.

  20. Release of Growth Factors into Root Canal by Irrigations in Regenerative Endodontics.

    PubMed

    Zeng, Qian; Nguyen, Sean; Zhang, Hongming; Chebrolu, Hari Priya; Alzebdeh, Dalia; Badi, Mustafa A; Kim, Jong Ryul; Ling, Junqi; Yang, Maobin

    2016-12-01

    The aim of this study was to investigate the release of growth factors into root canal space after the irrigation procedure of regenerative endodontic procedure. Sixty standardized root segments were prepared from extracted single-root teeth. Nail varnish was applied to all surfaces except the root canal surface. Root segments were irrigated with 1.5% NaOCl + 17% EDTA, 2.5% NaOCl + 17% EDTA, 17% EDTA, or deionized water. The profile of growth factors that were released after irrigation was studied by growth factor array. Enzyme-linked immunosorbent assay was used to validate the release of transforming growth factor (TGF)-β1 and basic fibroblast growth factor (bFGF) at 4 hours, 1 day, and 3 days after irrigation. The final concentrations were calculated on the basis of the root canal volume measured by cone-beam computed tomography. Dental pulp stem cell migration on growth factors released from root segments was measured by using Transwell assay. Total of 11 of 41 growth factors were detected by growth factors array. Enzyme-linked immunosorbent assay showed that TGF-β1 was released in all irrigation groups. Compared with the group with 17% EDTA (6.92 ± 4.49 ng/mL), the groups with 1.5% NaOCl + 17% EDTA and 2.5% NaOCl + 17% EDTA had significantly higher release of TGF-β1 (69.04 ± 30.41 ng/mL and 59.26 ± 3.37 ng/mL, respectively), with a peak release at day 1. The release of bFGF was detected at a low level in all groups (0 ng/mL to 0.43 ± 0.22 ng/mL). Migration assay showed the growth factors released from root segments induced dental pulp stem cell migration. The root segment model in present study simulated clinical scenario and indicated that the current irrigation protocol released a significant amount of TGF-β1 but not bFGF. The growth factors released into root canal space induced dental pulp stem cell migration. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  1. Hepatocyte Growth Factor/Scatter Factor Released during Peritonitis Is Active on Mesothelial Cells

    PubMed Central

    Rampino, Teresa; Cancarini, Giovanni; Gregorini, Marilena; Guallini, Paola; Maggio, Milena; Ranghino, Andrea; Soccio, Grazia; Dal Canton, Antonio

    2001-01-01

    Peritonitis causes mesothelial detachment that may result in persistent peritoneal denudation and fibrosis. We investigated whether hepatocyte growth factor (HGF), a scatter factor that induces detachment from substrate and fibroblastic transformation of several cell types, is produced during peritonitis and is active on mesothelial cells. We studied 18 patients on peritoneal dialysis, 9 uncomplicated, 9 with peritonitis. HGF was measured in serum, peritoneal fluid, and supernatant of peripheral blood mononuclear cells and peritoneal mononuclear cells. Primary culture of human peritoneal mesothelial cells and the human mesothelial cell line MeT-5A were conditioned with recombinant HGF, serum, and peritoneal fluid. HGF levels were significantly higher in serum and peritoneal fluid of peritonitic than uncomplicated patients. Mononuclear cells of peritonitic patients produced more HGF than cells of uncomplicated patients. Recombinant HGF, serum, and peritoneal fluid of peritonitic patients caused mesothelial cell growth, detachment, transformation from epithelial to fibroblast-like shape, overexpression of vimentin, and synthesis of type I and III collagen. In conclusion, HGF released during peritonitis causes a change in mesothelial cell phenotype and function. HGF may affect the healing process facilitating repair through mesothelial cell growth, but may contribute to peritoneal fibrosis inducing cell detachment with mesothelial denudation and collagen synthesis. PMID:11583955

  2. The Presence of Histamine and a Histamine Receptor in the Bivalve Mollusc, Crassostrea virginica

    PubMed Central

    Harrison, Jarreau; LaFleur, Kisha; Mantone, Daniel; Boisette, Beatrix; Harris, Ave; Catapane, Edward J.; Carroll, Margaret A.

    2015-01-01

    Histamine, a biogenic amine, is a neurotransmitter in neurons and sensory receptors in invertebrates. Histamine has rarely been reported in bivalves. We used HPLC with pre-column derivatization using 2,3-naphthalenedicarboxaldehyde (NDA) as a fluorescent labeling agent to measure histamine in ganglia, and peripheral tissues of the oyster Crassostrea virginica. We also used Western Blot technique to look for the presence of a histamine receptor in the mantle rim. HPLC results found histamine present in ng amounts in both the cerebral and visceral ganglia, as well as the mantle rim and other peripheral tissues of C. virginica. The study confirms and quantifies histamine as an endogenous biogenic amine in C. virginica in the nervous system and innervated organs. Western Blot technique also identified a histamine H2-like receptor present in sensory tissue of the oyster's mantle rim. PMID:26120600

  3. Temporally controlled release of multiple growth factors from a self-assembling peptide hydrogel

    NASA Astrophysics Data System (ADS)

    Bruggeman, Kiara F.; Rodriguez, Alexandra L.; Parish, Clare L.; Williams, Richard J.; Nisbet, David R.

    2016-09-01

    Protein growth factors have demonstrated great potential for tissue repair, but their inherent instability and large size prevents meaningful presentation to biologically protected nervous tissue. Here, we create a nanofibrous network from a self-assembling peptide (SAP) hydrogel to carry and stabilize the growth factors. We significantly reduced growth factor degradation to increase their lifespan by over 40 times. To control the temporal release profile we covalently attached polysaccharide chitosan molecules to the growth factor to increase its interactions with the hydrogel nanofibers and achieved a 4 h delay, demonstrating the potential of this method to provide temporally controlled growth factor delivery. We also describe release rate based analysis to examine the growth factor delivery in more detail than standard cumulative release profiles allow and show that the chitosan attachment method provided a more consistent release profile with a 60% reduction in fluctuations. To prove the potential of this system as a complex growth factor delivery platform we demonstrate for the first time temporally distinct release of multiple growth factors from a single tissue specific SAP hydrogel: a significant goal in regenerative medicine.

  4. Histamine H4 and H1 receptors contribute to postinflammatory visceral hypersensitivity.

    PubMed

    Deiteren, Annemie; De Man, Joris G; Ruyssers, Nathalie E; Moreels, Tom G; Pelckmans, Paul A; De Winter, Benedicte Y

    2014-12-01

    Substantial evidence implicates mast cells and their main constituent histamine in the pathogenesis of visceral hypersensitivity. We explored the specific contribution of histamine H4 (H4R) and H1 (H1R) receptors to visceral hypersensitivity in a postinflammatory rat model. Trinitrobenzenesulfonic acid (TNBS)-colitis was monitored individually by colonoscopy: first on day 3 to confirm the presence of colitis and then every 4 days, starting from day 10, to monitor convalescence and determine the exact timepoint of endoscopic healing in each rat. Experiments were performed 3 days after endoscopic resolution of colitis. Visceral sensitivity was assessed by quantifying visceromotor responses (VMRs) to colorectal distension. Colonic mast cell numbers, histamine release and H4R and H1R mRNA expression were quantified. JNJ7777120 (H4R antagonist) and/or levocetirizine (H1R antagonist) were administered 30 min prior to VMR assessment or histamine release assay. Postcolitis rats displayed a higher number of colonic mast cells, excessive histamine release and significantly enhanced VMRs. Heightened VMRs were dose-dependently reduced by JNJ7777120 and levocetirizine; combined administration of JNJ7777120 and levocetirizine potentiated the antinociceptive effect. In the colon, both H4R and H1R mRNA were present; in the dorsal root ganglia, only H1R mRNA was found. Only colonic H4R mRNA expression was increased in postcolitis rats. Excessive histamine release in postcolitis rats was attenuated by the highest dose of JNJ7777120. H4R and H1R antagonists dose-dependently reduce and even normalise postinflammatory visceral hypersensitivity via different underlying mechanisms but with a synergistic effect. Both receptor subtypes represent promising targets for the treatment of postinflammatory visceral hypersensitivity. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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

    SciTech Connect

    Donlon, M.A.; Melia, J.A.; Helgeson, E.A.; Wolfe, W.W.

    1986-03-01

    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.

  6. Fluorometric determination of histamine in cheese.

    PubMed

    Chambers, T L; Staruszkiewicz, W F

    1978-09-01

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

  7. Diets High in Heat-Treated Soybean Meal Reduce the Histamine-Induced Epithelial Response in the Colon of Weaned Piglets and Increase Epithelial Catabolism of Histamine

    PubMed Central

    Kröger, Susan; Pieper, Robert; Schwelberger, Hubert G.; Wang, Jing; Villodre Tudela, Carmen; Aschenbach, Jörg R.; Van Kessel, Andrew G.; Zentek, Jürgen

    2013-01-01

    We examined the influence of dietary fermentable protein (fCP) and fermentable carbohydrates (fCHO) on the colonic epithelial response to histamine in pigs. Thirty-two weaned piglets were fed 4 diets in a 2 × 2 factorial design with low fCP/low fCHO, low fCP/high fCHO, high fCP/low fCHO and high fCP/high fCHO. After 21-23 days, the pigs were killed and tissue from the proximal colon was stimulated with carbachol, histamine, PGE2 or sodium hydrogen sulphide in Ussing chambers. Changes in short-circuit current and tissue conductance were measured. Diamine oxidase, histamine N-methyltransferase, stem cell growth factor receptor, Fc-epsilon receptor I and cystic fibrosis transmembrane conductance regulator gene expression was determined. Activities of diamine oxidase and histamine N-methyltransferase and numbers of colonic mast cells were measured. The change in the short-circuit current in response to histamine was lower (P = 0.002) and tended to be lower for PGE2 (P = 0.053) in high fCP groups compared to low fCP groups, irrespective of fCHO. Additionally, the change in tissue conductance after the application of histamine was lower (P = 0.005) in the high fCP groups. The expression of histamine N-methyltransferase mRNA (P = 0.033) and the activities of diamine oxidase (P = 0.001) and histamine N-methyltransferase (P = 0.006) were higher with high fCP in comparison with low fCP. The expression of mast cell markers, stem cell growth factor receptor (P = 0.005) and Fc-epsilon receptor I (P = 0.049) was higher with high fCP diets compared to diets low in fCP, whereas the mast cell count did not differ between groups. The expression of the cystic fibrosis transmembrane conductance regulator was reduced (P = 0.001) with high fCP diets compared to low fCP diets. The lower epithelial response to histamine and PGE2 and elevated epithelial histamine inactivation suggests an adaptation to high fCP diets. PMID:24260435

  8. Influence of factors on release of antimicrobials from antimicrobial packaging materials.

    PubMed

    Wu, Yu-Mei; Wang, Zhi-Wei; Hu, Chang-Ying; Nerín, Cristina

    2016-10-13

    Antimicrobial packaging materials (films or coatings) (APMs) have aroused great interest among the scientists or the experts specialized in material science, food science, packaging engineering, biology and chemistry. APMs have been used to package the food, such as dairy products, poultry, meat (e.g., beef), salmon muscle, pastry dough, fresh pasta, bakery products, fruits, vegetables and beverages. Some materials have been already commercialized. The ability of APMs to extend the shelf-life of the food depends on the release rate of the antimicrobials (AMs) from the materials to the food. The optimum rate is defined as target release rate (TRR). To achieve TRR, the influencing factors of the release rate should be considered. Herein we reviewed for the first time these factors and their influence on the release. These factors mainly include the AMs, food (or food simulant), packaging materials, the interactions among them, the temperature and environmental relative humidity (RH).

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

    SciTech Connect

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

    1982-06-01

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

  10. Mast cells mediate acid-induced augmentation of opossum esophageal blood flow via histamine and nitric oxide.

    PubMed

    Feldman, M J; Morris, G P; Dinda, P K; Paterson, W G

    1996-01-01

    Increased esophageal blood flow during reflux episodes may play an important role in mucosal resistance to injury, although the mechanism remains unclear. Decreased stainable mast cells and increased luminal histamine release during acid exposure has been previously documented. Therefore, the role of mast cells, nerves, histamine, and nitric oxide in mediating increased blood flow during acid challenge of the distal esophagus was investigated. The effects of the mast cell stabilizers disodium cromoglycate and doxantrazole, the neurotoxin tetrodotoxin, the histamine H1 receptor antagonist promethazine, and the NO synthase inhibitor N omega-nitro-L-arginine methyl ester were examined by monitoring opossum esophageal histamine release and blood flow during perfusion with 100 mmol/L HCl. Luminal acid challenge significantly increased both histamine release and blood flow (P < 0.05). Disodium cromoglycate, promethazine, and N omega-nitro-L-arginine methyl ester attenuated the increase in blood flow to basal (saline-perfused) levels. Tetrodotoxin did not prevent an acute increase in blood flow that rapidly returned to baseline, likely from the ensuing hypotension. These findings provide evidence that mast cell-derived histamine, acting through an NO-dependent mechanism, plays a central role in the response of the esophageal microcirculation to luminal acid.

  11. Mast cells and histamine are triggering the NF-κB-mediated reactions of adult and aged perilymphatic mesenteric tissues to acute inflammation

    PubMed Central

    Nizamutdinova, Irina Tsoy; Dusio, Giuseppina F.; Gasheva, Olga Yu.; Skoog, Hunter; Tobin, Richard; Peddaboina, Chander; Meininger, Cynthia J.; Zawieja, David C.; Newell-Rogers, M. Karen; Gashev, Anatoliy A.

    2016-01-01

    This study aimed to establish mechanistic links between the aging-associated changes in the functional status of mast cells and the altered responses of mesenteric tissue and mesenteric lymphatic vessels (MLVs) to acute inflammation. We used an in vivo model of acute peritoneal inflammation induced by lipopolysaccharide treatment of adult (9-month) and aged (24-month) F-344 rats. We analyzed contractility of isolated MLVs, mast cell activation, activation of nuclear factor-κB (NF-κB) without and with stabilization of mast cells by cromolyn or blockade of all types of histamine receptors and production of 27 major pro-inflammatory cytokines in adult and aged perilymphatic mesenteric tissues and blood. We found that the reactivity of aged contracting lymphatic vessels to LPS-induced acute inflammation was abolished and that activated mast cells trigger NF-κB signaling in the mesentery through release of histamine. The aging-associated basal activation of mesenteric mast cells limits acute inflammatory NF-κB activation in aged mesentery. We conclude that proper functioning of the mast cell/histamine/NF-κB axis is necessary for reactions of the lymphatic vessels to acute inflammatory stimuli as well as for interaction and trafficking of immune cells near and within the collecting lymphatics. PMID:27875806

  12. Histamine H3-receptor isoforms.

    PubMed

    Bakker, R A

    2004-10-01

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

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

    PubMed Central

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

    2010-01-01

    The preoptic area/anterior hypothalamus (PO/AH), a region that contains neurons that control thermoregulation, is the main locus at which histamine affects body temperature. Here we report that histamine reduced the spontaneous firing rate of GABAergic preoptic neurons by activating H3 subtype histamine receptors. This effect involved a decrease in the level of phosphorylation of the extracellular signal-regulated kinase (ERK) and was not dependent on synaptic activity. Furthermore, a population of nonGABAergic neurons was depolarized and their firing rate was enhanced by histamine acting at H1 subtype receptors. In our experiments, activation of the H1R receptors was linked to the PLC pathway and Ca2+ release from intracellular stores. This depolarization persisted in TTX or when fast synaptic potentials were blocked indicating that it represents a postsynaptic effect. Single-cell reverse transcription –PCR analysis revealed expression of H3 receptors in a population of GABAergic neurons while H1 receptors were expressed in nonGABAergic cells. Histamine applied in the median preoptic nucleus induced a robust, long lasting hyperthermia effect that was mimicked by either H1 or H3 histamine receptor subtype specific agonists. Our data indicate that histamine modulates the core body temperature by acting at two distinct populations of preoptic neurons which express H1 and H3 receptor subtypes, respectively. PMID:20335473

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

    PubMed

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

    2010-03-24

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

  15. Polymethylmethacrylate-induced release of bone-resorbing factors

    SciTech Connect

    Herman, J.H.; Sowder, W.G.; Anderson, D.; Appel, A.M.; Hopson, C.N. )

    1989-12-01

    A pseudomembranous structure that has the histological characteristics of a foreign-body-like reaction invariably develops at the bone-cement interface in the proximity of resorption of bone around aseptically loosened cemented prostheses. This study was an attempt to implicate polymethylmethacrylate in this resorptive process. Unfractionated peripheral-blood mononuclear cells (consisting of lymphocytes and monocytes) and surface-adherent cells (monocyte-enriched) were prepared from control subjects who did and did not have clinical evidence of osteoarthrosis and from patients who had osteoarthrosis and were having a revision for failure of a cemented hip or knee implant. Cells were cultured for varying periods in the presence and absence of nonpolymerized methacrylate (one to two-micrometer spherules), pulverized polymerized material, or culture chambers that were pre-coated with polymerized cement. Conditioned media that were derived from both methacrylate-stimulated cell populations were shown to contain specific bone-resorbing mediators (interleukin-1, tumor necrosis factor, or prostaglandin E2) and to directly affect bone resorption in 45Ca-labeled murine limb-bone assays.

  16. Mast Cells Synthesize, Store, and Release Nerve Growth Factor

    NASA Astrophysics Data System (ADS)

    Leon, A.; Buriani, A.; dal Toso, R.; Fabris, M.; Romanello, S.; Aloe, L.; Levi-Montalcini, R.

    1994-04-01

    Mast cells and nerve growth factor (NGF) have both been reported to be involved in neuroimmune interactions and tissue inflammation. In many peripheral tissues, mast cells interact with the innervating fibers. Changes in the behaviors of both of these elements occur after tissue injury/inflammation. As such conditions are typically associated with rapid mast cell activation and NGF accumulation in inflammatory exudates, we hypothesized that mast cells may be capable of producing NGF. Here we report that (i) NGF mRNA is expressed in adult rat peritoneal mast cells; (ii) anti-NGF antibodies clearly stain vesicular compartments of purified mast cells and mast cells in histological sections of adult rodent mesenchymal tissues; and (iii) medium conditioned by peritoneal mast cells contains biologically active NGF. Mast cells thus represent a newly recognized source of NGF. The known actions of NGF on peripheral nerve fibers and immune cells suggest that mast cell-derived NGF may control adaptive/reactive responses of the nervous and immune systems toward noxious tissue perturbations. Conversely, alterations in normal mast cell behaviors may provoke maladaptive neuroimmune tissue responses whose consequences could have profound implications in inflammatory disease states, including those of an autoimmune nature.

  17. Effect of c-kit ligand, stem cell factor, on mediator release by human intestinal mast cells isolated from patients with inflammatory bowel disease and controls.

    PubMed Central

    Bischoff, S C; Schwengberg, S; Wordelmann, K; Weimann, A; Raab, R; Manns, M P

    1996-01-01

    The regulation of mediator release in human intestinal mast cells is largely unknown. Apart from IgE receptor crosslinking no secretagogues have been described so far. This study examined the effect of two cytokines (c-kit ligand and interleukin 3) and other agonists on human intestinal mast cell function. Cells were isolated from surgery specimens of 47 patients undergoing intestinal resection because of tumours or inflammatory bowel disease. Cell suspensions contained 3.6% mast cells (mean of 50 experiments). After preincubation without or with c-kit ligand or interleukin 3, cells were stimulated by IgE receptor crosslinking, C5a or formyl-methionyl-leucyl-phenylalanine (fMLP). Histamine and sulphidoleukotriene release was measured in supernatants. The sequential stimulation of the cells with c-kit ligand and IgE receptor crosslinking induced the release of high amounts of histamine and leukotrienes, whereas each agonist by itself induced only marginal mediator release. Interleukin 3 induced no release by itself, but enhanced the IgE receptor dependent release, possibly by an indirect mechanism. No significant mediator release was seen in response to C5a and fMLP, even if the cells were pretreated with c-kit ligand. The mediator release, particularly that of leukotrienes, was higher in cells isolated from actively inflamed tissue from patients with inflammatory bowel disease compared with controls. In conclusion, it was found that, apart from IgE receptor crosslinking, c-kit ligand and interleukin 3 regulate mediator release in human intestinal mast cells. The enhancement of mediator release by cytokines may be of particular relevance in the pathogenesis of inflammatory bowel diseases and food intolerance reactions. PMID:8566835

  18. Functional characteristics of histamine receptor-bearing mononuclear cells. II. Identification and characterization of two histamine-induced human lymphokines that inhibit lymphocyte migration.

    PubMed

    Berman, J S; McFadden, R G; Cruikshank, W W; Center, D M; Beer, D J

    1984-09-01

    Although functional histamine receptors have generally been restricted to those human T lymphocytes expressing suppressor cell functions, more recent evidence suggests that histamine receptor-bearing human T lymphocytes are functionally heterogeneous and capable of other immunomodulatory activities. Lymphocyte chemoattractant factor (LCF) is a cationic sialoprotein with an apparent m.w. of 56,000, whose production is limited to histamine-type 2 receptor-bearing human T cells. LCF is selectively chemokinetic for T lymphocytes, and presumably contributes to the recruitment of unsensitized effector lymphocytes at inflammatory sites. In addition to LCF, Sephadex G-100 gel filtration of histamine-induced lymphocyte supernatants revealed two regions of migration inhibitory activity for human blood T and rat splenic lymphocytes. These regions corresponded to m.w. of 70,000 to 80,000 (LyMIF75K) and 30,000 to 40,000 (LyMIF35K). LyMIF75K had a single pI of 7.5 to 8.0, and its biologic activity was sensitive to trypsin but not to neuraminidase or heat (56 degrees C). LyMIF35K had a single pI of 8.5 to 8.8, and its biologic activity was sensitive to neuraminidase and heat but not to trypsin. These LyMIFs therefore appeared to be distinct from one another and physicochemically different from other migration inhibitory lymphokines. All three lymphokine activities appeared within 4 hr of incubation. The minimum concentration of histamine required to stimulate production of the LyMIF was 10(-6) M. Lymphocytes that did not adhere to a histamine affinity matrix were unable to produce either LyMIF upon subsequent stimulation with histamine or concanavalin A (Con A). Lymphocytes incubated with histamine and diphenhydramine produced LCF but neither LyMIF, whereas cells incubated with histamine in the presence of cimetidine produced both LyMIF but not LCF. These data suggest that a subset of lymphocytes defined by the presence of histamine-type 1 receptors are capable of producing two

  19. Peptide Chain Termination: Effect of Protein S on Ribosomal Binding of Release Factors

    PubMed Central

    Goldstein, J. L.; Caskey, C. T.

    1970-01-01

    The protein factor S, previously shown to stimulate polypeptide chain termination in bacterial extracts, has two effects upon the complex formed between ribosomes, release factor, and terminator (trinucleotide) codon: (1) in the absence of GTP or GDP, S stimulates formation of an [R·UAA·ribosome] intermediate, and (2) in the presence of GTP or GDP, S participates in dissociation of this intermediate. Factor S can stimulate fMet release from [fMet-tRNAf·AUG·ribosome] intermediates in either the presence or absence of GTP or GDP. A model is proposed which relates the in vitro effects of S ± GTP (or GDP) on fMet release to the effects of S ± GTP (or GDP) on the binding and dissociation of R factor from ribosomes. PMID:5289007

  20. Psycho-Social Factors as Predictors of Success in a Work-Release Program.

    ERIC Educational Resources Information Center

    Brahen, Leonard S.; And Others

    1979-01-01

    Investigates the significance of social and environmental factors as predictors of the rehabilitative potential of an inmate. Work history must be used as a whole. The more recent a good history, the more successful an inmate's jail record. Work factors may aid in selecting narcotics-addicted inmates for work-release programs. (Author/BEF)

  1. Psycho-Social Factors as Predictors of Success in a Work-Release Program.

    ERIC Educational Resources Information Center

    Brahen, Leonard S.; And Others

    1979-01-01

    Investigates the significance of social and environmental factors as predictors of the rehabilitative potential of an inmate. Work history must be used as a whole. The more recent a good history, the more successful an inmate's jail record. Work factors may aid in selecting narcotics-addicted inmates for work-release programs. (Author/BEF)

  2. Control of angiogenesis by galectins involves the release of platelet-derived proangiogenic factors.

    PubMed

    Etulain, Julia; Negrotto, Soledad; Tribulatti, María Virginia; Croci, Diego Omar; Carabelli, Julieta; Campetella, Oscar; Rabinovich, Gabriel Adrián; Schattner, Mirta

    2014-01-01

    Platelets contribute to vessel formation through the release of angiogenesis-modulating factors stored in their α-granules. Galectins, a family of lectins that bind β-galactoside residues, are up-regulated in inflammatory and cancerous tissues, trigger platelet activation and mediate vascularization processes. Here we aimed to elucidate whether the release of platelet-derived proangiogenic molecules could represent an alternative mechanism through which galectins promote neovascularization. We show that different members of the galectin family can selectively regulate the release of angiogenic molecules by human platelets. Whereas Galectin (Gal)-1, -3, and -8 triggered vascular endothelial growth factor (VEGF) release, only Gal-8 induced endostatin secretion. Release of VEGF induced by Gal-8 was partially prevented by COX-1, PKC, p38 and Src kinases inhibitors, whereas Gal-1-induced VEGF secretion was inhibited by PKC and ERK blockade, and Gal-3 triggered VEGF release selectively through a PKC-dependent pathway. Regarding endostatin, Gal-8 failed to stimulate its release in the presence of PKC, Src and ERK inhibitors, whereas aspirin or p38 inhibitor had no effect on endostatin release. Despite VEGF or endostatin secretion, platelet releasates generated by stimulation with each galectin stimulated angiogenic responses in vitro including endothelial cell proliferation and tubulogenesis. The platelet angiogenic activity was independent of VEGF and was attributed to the concerted action of other proangiogenic molecules distinctly released by each galectin. Thus, secretion of platelet-derived angiogenic molecules may represent an alternative mechanism by which galectins promote angiogenic responses and its selective blockade may lead to the development of therapeutic strategies for angiogenesis-related diseases.

  3. Control of Angiogenesis by Galectins Involves the Release of Platelet-Derived Proangiogenic Factors

    PubMed Central

    Etulain, Julia; Negrotto, Soledad; Tribulatti, María Virginia; Croci, Diego Omar; Carabelli, Julieta; Campetella, Oscar; Rabinovich, Gabriel Adrián; Schattner, Mirta

    2014-01-01

    Platelets contribute to vessel formation through the release of angiogenesis-modulating factors stored in their α-granules. Galectins, a family of lectins that bind β-galactoside residues, are up-regulated in inflammatory and cancerous tissues, trigger platelet activation and mediate vascularization processes. Here we aimed to elucidate whether the release of platelet-derived proangiogenic molecules could represent an alternative mechanism through which galectins promote neovascularization. We show that different members of the galectin family can selectively regulate the release of angiogenic molecules by human platelets. Whereas Galectin (Gal)-1, -3, and -8 triggered vascular endothelial growth factor (VEGF) release, only Gal-8 induced endostatin secretion. Release of VEGF induced by Gal-8 was partially prevented by COX-1, PKC, p38 and Src kinases inhibitors, whereas Gal-1-induced VEGF secretion was inhibited by PKC and ERK blockade, and Gal-3 triggered VEGF release selectively through a PKC-dependent pathway. Regarding endostatin, Gal-8 failed to stimulate its release in the presence of PKC, Src and ERK inhibitors, whereas aspirin or p38 inhibitor had no effect on endostatin release. Despite VEGF or endostatin secretion, platelet releasates generated by stimulation with each galectin stimulated angiogenic responses in vitro including endothelial cell proliferation and tubulogenesis. The platelet angiogenic activity was independent of VEGF and was attributed to the concerted action of other proangiogenic molecules distinctly released by each galectin. Thus, secretion of platelet-derived angiogenic molecules may represent an alternative mechanism by which galectins promote angiogenic responses and its selective blockade may lead to the development of therapeutic strategies for angiogenesis-related diseases. PMID:24788652

  4. Endothelium-Derived Hyperpolarizing Factor Mediates Bradykinin Stimulated Tissue Plasminogen Activator Release In Humans

    PubMed Central

    Rahman, Ayaz M.; Murrow, Jonathan R.; Ozkor, Muhiddin A.; Kavtaradze, Nino; Lin, Ji; De Staercke, Christine; Hooper, W. Craig; Manatunga, Amita; Hayek, Salim; Quyyumi, Arshed A.

    2014-01-01

    Aims Bradykinin stimulates tissue plasminogen activator (t-PA) release from human endothelium. Although bradykinin stimulates both nitric oxide and endothelium-derived hyperpolarizing factor (EDHF) release, the role of EDHF in t-PA release remains unexplored. This study sought to determine the mechanisms of bradykinin-stimulated t-PA release in the forearm vasculature of healthy human subjects. Methods In 33 healthy subjects (age 40.3±1.9 years) forearm blood flow (FBF) and t-PA release were measured at rest, and after intra-arterial infusions of bradykinin (400ng/min) and sodium nitroprusside (3.2 mg/min). Measurements were repeated after intra-arterial infusion of TEA (1 μmol/min), fluconazole (0.4 μmol.min-1.L-1), and NG-monomethyl-L-arginine (L-NMMA, 8 μmol/min) to block nitric oxide, and their combination in separate studies. Results Bradykinin significantly increased net t-PA release across the forearm (P<0.0001). Fluconazole attenuated both bradykinin-mediated vasodilation (-23.3±2.7% FBF, P<0.0001) and t-PA release (from 50.9±9.0 to 21.3±8.9 ng/min/100ml, P=0.02). TEA attenuated FBF (-14.7±3.2%, P=0.002) and abolished bradykinin-stimulated t-PA release (from 22.9+5.7 to - 0.8±3.6 ng/min/100ml, P=0.0002). L-NMMA attenuated FBF (P<0.0001), but did not inhibit bradykinin-induced t-PA release (P=NS). Conclusion Bradykinin-stimulated t-PA release is partly due to cytochrome P450-derived epoxides, and is inhibited by K+ca channel blockade. Thus, bradykinin stimulates both EDHF-dependent vasodilation and t-PA release. PMID:24925526

  5. Controllable mineral coatings on PCL scaffolds as carriers for growth factor release

    PubMed Central

    Suárez-González, Darilis; Barnhart, Kara; Migneco, Francesco; Flanagan, Colleen; Hollister, Scott J.; Murphy, William L.

    2011-01-01

    In this study, we have developed mineral coatings on polycaprolactone scaffolds to serve as templates for growth factor binding and release. Mineral coatings were formed using a biomimetic approach that consisted in the incubation of scaffolds in modified simulated body fluids (mSBF). To modulate the properties of the mineral coating, which we hypothesized would dictate growth factor release, we used carbonate (HCO3) concentration in mSBF of 4.2 mM, 25mM, and 100mM. Analysis of the mineral coatings formed using scanning electron microscopy indicated growth of a continuous layer of mineral with different morphologies. X-ray diffraction analysis showed peaks associated with hydroxyapatite, the major inorganic constituent of human bone tissue in coatings formed in all HCO3 concentrations. Mineral coatings with increased HCO3 substitution showed more rapid dissolution kinetics in an environment deficient in calcium and phosphate but showed re-precipitation in an environment with the aforementioned ions. The mineral coating provided an effective mechanism for growth factor binding and release. Peptide versions of vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP2) were bound with efficiencies up to 90% to mineral mineral-coated PCL scaffolds. We also demonstrated sustained release of all growth factors with release kinetics that were strongly dependent in the solubility of the mineral coating. PMID:22014948

  6. Gas chromatographic analysis of histamine in mahi-mahi (Coryphaena hippurus).

    PubMed

    Antoine, Francis R; Wei, Cheng-I; Otwell, W Steve; Sims, Charlie A; Littell, Ramon C; Hogle, Amanda D; Marshall, Maurice R

    2002-08-14

    Several authors have studied histamine using gas chromatography (GC) as a tool for quantitation, but the methods used were not always suitable depending on the kind of food. Problems frequently cited include incomplete histamine elution from the columns and peak tailing. Histamine is of interest because it is the factor common to all cases of scombroid poisoning, it has physiological and biological activity, and it is a chemical indicator of fish quality. In this study a modified GC method was used to quantify histamine in mahi-mahi (Coryphaena hippurus). Mean recovery was 67% for the GC method, compared with 90% for the AOAC fluorometric method. There was a 0.96 correlation of the GC histamine values with those of the AOAC fluorometric method. A temperature program, splitless/split injection, and analyte cleanup were essential for GC properties. Histamine retention time was 8.2 min. The method allowed peak height to be used for quantitation and simultaneous analysis of cadaverine and putrescine.

  7. Inhaled histamine increases the rate of absorption of sodium cromoglycate from the lung.

    PubMed Central

    Richards, R; Fowler, C; Simpson, S; Renwick, A G; Holgate, S T

    1992-01-01

    Since many factors may alter lung epithelial permeability (LEP) to water soluble molecules, the effect of histamine on the absorption and clearance of inhaled sodium cromoglycate was examined in seven mildly asthmatic patients with hyperresponsive airways and eight normal subjects. The subjects underwent histamine challenge to determine the provocative concentration of histamine required to reduce the forced expiratory volume in one second (FEV1) by 20% (PC20) from baseline. On two further visits they inhaled either saline placebo or histamine and 5 min later inhaled an aerosol containing sodium cromoglycate. Measurements of FEV1 were made and blood samples taken for analysis of plasma sodium cromoglycate concentration at intervals for 3 h. In the asthmatic group histamine inhalation led to a 24 +/- 4% reduction in FEV1 but had no effect on the normal subjects. When compared with inhaled saline, histamine increased the initial pulmonary absorption of SCG without influencing the total amount of drug absorbed in both asthmatics and normals. These observations suggest that the pharmacokinetics of inhaled sodium cromoglycate may be altered significantly by inflammatory mediators present at the site of drug absorption from the airways. PMID:1576060

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

    PubMed Central

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

    1988-01-01

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

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

    ERIC Educational Resources Information Center

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

    2010-01-01

    Memory that food is inedible in "Aplysia" arises from training requiring three contingent events. Nitric oxide (NO) and histamine are released by a neuron responding to one of these events, attempts to swallow food. Since NO release during training is necessary for subsequent memory and NO substitutes for attempts to swallow, it was suggested that…

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

    ERIC Educational Resources Information Center

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

    2010-01-01

    Memory that food is inedible in "Aplysia" arises from training requiring three contingent events. Nitric oxide (NO) and histamine are released by a neuron responding to one of these events, attempts to swallow food. Since NO release during training is necessary for subsequent memory and NO substitutes for attempts to swallow, it was suggested that…

  11. Analytical Methods for the Quantification of Histamine and Histamine Metabolites.

    PubMed

    Bähre, Heike; Kaever, Volkhard

    2017-03-21

    The endogenous metabolite histamine (HA) is synthesized in various mammalian cells but can also be ingested from exogenous sources. It is involved in a plethora of physiological and pathophysiological processes. So far, four different HA receptors (H1R-H4R) have been described and numerous HAR antagonists have been developed. Contemporary investigations regarding the various roles of HA and its main metabolites have been hampered by the lack of highly specific and sensitive analytic methods for all of these analytes. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) is the method of choice for identification and sensitive quantification of many low-molecular weight endogenous metabolites. In this chapter, different methodological aspects of HA quantification as well as recommendations for LC-MS/MS methods suitable for analysis of HA and its main metabolites are summarized.

  12. New concepts of histamine receptors and actions.

    PubMed

    Repka-Ramirez, Maria Susana

    2003-05-01

    Histamine and antihistamines are so deeply woven into the fabric of allergic diseases that it is sometimes difficult to see how this field could advance beyond our current, potent histamine H1-receptor drugs. Investigations of other actions of histamine and the identification of H2, H3, and now H4 receptors have suddenly reignited the search for new mono- and multi-receptor-specific agonists and antagonists. There is great excitement due to preliminary findings that H3 receptors act as neural inhibitory autoreceptors, and H4 receptors might modulate immune cell functions.

  13. Synthesis of histamine by Haemophilus influenzae.

    PubMed

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

    1986-03-29

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

  14. Synthesis of histamine by Haemophilus influenzae.

    PubMed Central

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

    1986-01-01

    Recent findings suggest that bacteria might contribute to histamine concentrations in the sputum of patients with infective lung disease. Ten isolates of Haemophilus influenzae from patients with acute exacerbation of chronic bronchitis and emphysema, together with two reference strains, were incubated at 37 degrees C for 72 hours. Serial estimations of histamine concentrations by high pressure liquid chromatography showed significant increases at 24 and 48 hours; no increases were evident in the control samples. These findings suggest that H influenzae might contribute to inflammation and limited airflow in infective lung disease by producing histamine. PMID:3083910

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

    PubMed Central

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

    1992-01-01

    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 contractile response to histamine was antagonized by the histamine H1-receptor antagonist, clemizole (0.1 microM) but was potentiated by the histamine H2-receptor antagonist, ranitidine (10 microM). Clemizole (0.1 nM to 10 nM) competitively antagonized the contractile effect of 2-pyridylethylamine (- log KB = 10.5 +/- 0.5). The concentration-response curve for acetylcholine was displaced to the right by atropine 0.1 microM. 4. Atropine (0.1 microM), propranolol (0.1 microM), prazosin (0.1 microM) and indomethacin (1 microM) failed to modify the contractile response to histamine. 5. In human isolated myometrial strips precontracted with KCl (55 mM), clemizole at 1 microM completely abolished the contractile response to histamine and revealed a concentration-dependent relaxation. Dimaprit alone and 4-methylhistamine (in the presence of clemizole), produced concentration-related relaxation with a magnitude similar to that in response to histamine. The relaxant response to dimaprit was antagonized by ranitidine. 6. It is concluded that human isolated uterine strips possess histamine H1- and H2-receptors: the former mediating contraction and the latter relaxation. The predominant response to histamine in this tissue is contraction. PMID:1358393

  16. Effects of chronic stress on anterior pituitary and brain corticotropin-releasing factor receptors.

    PubMed

    Anderson, S M; Kant, G J; De Souza, E B

    1993-04-01

    [125I]Corticotropin-releasing factor binding was measured in membrane homogenates prepared from the anterior pituitary, frontal cortex, motor cortex, somatosensory cortex, mesolimbic area (olfactory tubercle and nucleus accumbens), caudate putamen, hypothalamus, midbrain, and cerebellum from control and chronically stressed rats. The stressor consisted of 3 or 14 days of around-the-clock intermittent foot-shock (approximately one trial per 5-min frequency) that could be avoided or escaped on 90% of the trials presented by pulling a ceiling chain. Plasma corticosterone levels were almost doubled in stressed rats following 3 days of chronic stress and remained significantly elevated in rats stressed for 14 days as compared to controls. Plasma corticotropin levels were similar in controls and stressed animals in both the 3- and 14-day experiments. [125I]Corticotropin-releasing factor binding was decreased in anterior pituitary and frontal cortex following 3 days of chronic stress; binding affinity of anterior pituitary membranes was not different between control and stressed animals. [125I]Corticotropin-releasing factor binding was similar in control and 3-day-stressed animals in the other brain areas examined. After 14 days of chronic stress, hypothalamic [125I]corticotropin-releasing factor binding was decreased in stressed rats as compared to control animals but no other differences were seen. The decrease in the apparent number of anterior pituitary corticotropin-releasing factor receptors following 3 days of stress may be due, in part, to increased plasma corticosterone levels and/or increased corticotropin-releasing factor secretion during that time.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Effects of release factor context at UAA codons in Escherichia coli.

    PubMed Central

    Martin, R; Weiner, M; Gallant, J

    1988-01-01

    In Escherichia coli, nonsense suppression at UAA codons is governed by the competition between a suppressor tRNA and the translational release factors RF1 and RF2. We have employed plasmids carrying the genes for RF1 and RF2 to measure release factor preference at UAA codons at 13 different sites in the lacI gene. We show here that the activity of RF1 and RF2 varies according to messenger context. RF1 is favored at UAA codons which are efficiently suppressed. RF2 is preferred at poorly suppressed sites. PMID:3049546

  18. Histamine-mediated Increases in Cytosolic [Ca2+] Involve Different Mechanisms in Human Pulmonary Artery Smooth Muscle and Endothelial Cells

    PubMed Central

    Mauban, Joseph R. H.; Wilkinson, Katherine; Schach, Christian; Yuan, Jason X.-J.

    2005-01-01

    Agonist stimulation of human pulmonary artery smooth muscle (PASMC) and endothelial (PAEC) cells with histamine showed similar spatiotemporal patterns of Ca2+ release. Both sustained elevation and oscillatory patterns of changes in cytosolic Ca2+ concentration ([Ca2+]cyt) were observed in the absence of extracellular Ca2+. Capacitative Ca2+ entry (CCE) was induced in PASMC and PAEC by passive depletion of intracellular Ca2+ stores with 10-μM cyclopiazonic acid (CPA, for 15-30 min). The pyrazole derivative BTP2 inhibited the CPA-activated Ca2+ influx, suggesting that depletion of CPA-sensitive internal stores is sufficient to induce CCE in both PASMC and PAEC. The recourse of histamine-mediated Ca2+ release was examined after exposure of the cells to CPA, thapsigargin, caffeine, ryanodine, FCCP, or bafilomycin. In PASMC bathed in Ca2+-free solution, treatment with CPA almost abolished histamine-induced rises in [Ca2+]cyt. In PAEC bathed in Ca2+-free solution, however, treatment with CPA eliminated the histamine-induced sustained and oscillatory rises in [Ca2+]cyt, but did not affect the initial transient increase in [Ca2+]cyt. Furthermore, treatment of PAEC with a combination of CPA (or thapsigargin) and caffeine (and ryanodine), FCCP, or bafilomycin did not abolish the histamine-induced transient [Ca2+]cyt increases. These observations indicate that a) depletion of CPA-sensitive stores is sufficient to cause CCE in both PASMC and PAEC; b) induction of CCE in PAEC does not require depletion of all internal Ca2+ stores; c) the histamine-releasable internal stores in PASMC are mainly CPA-sensitive stores; d) PAEC, in addition to a functional pool that is sensitive to CPA, contain other stores that are insensitive to CPA, thapsigargin, caffeine, ryanodine, FCCP, and bafilomycin; and e) the CPA-insensitive stores in PAEC, while may not contribute to CCE, contribute to histamine-mediated Ca2+ release. PMID:16162658

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

    PubMed

    Malinowska, B; Godlewski, G; Schlicker, E

    1998-06-01

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

  20. Gelatin-based hydrogel for vascular endothelial growth factor release in peripheral nerve tissue engineering.

    PubMed

    Gnavi, S; di Blasio, L; Tonda-Turo, C; Mancardi, A; Primo, L; Ciardelli, G; Gambarotta, G; Geuna, S; Perroteau, I

    2017-02-01

    Hydrogels are promising materials in regenerative medicine applications, due to their hydrophilicity, biocompatibility and capacity to release drugs and growth factors in a controlled manner. In this study, biocompatible and biodegradable hydrogels based on blends of natural polymers were used in in vitro and ex vivo experiments as a tool for VEGF-controlled release to accelerate the nerve regeneration process. Among different candidates, the angiogenic factor VEGF was selected, since angiogenesis has been long recognized as an important and necessary step during tissue repair. Recent studies have pointed out that VEGF has a beneficial effect on motor neuron survival and Schwann cell vitality and proliferation. Moreover, VEGF administration can sustain and enhance the growth of regenerating peripheral nerve fibres. The hydrogel preparation process was optimized to allow functional incorporation of VEGF, while preventing its degradation and denaturation. VEGF release was quantified through ELISA assay, whereas released VEGF bioactivity was validated in human umbilical vein endothelial cells (HUVECs) and in a Schwann cell line (RT4-D6P2T) by assessing VEGFR-2 and downstream effectors Akt and Erk1/2 phosphorylation. Moreover, dorsal root ganglia explants cultured on VEGF-releasing hydrogels displayed increased neurite outgrowth, providing confirmation that released VEGF maintained its effect, as also confirmed in a tubulogenesis assay. In conclusion, a gelatin-based hydrogel system for bioactive VEGF delivery was developed and characterized for its applicability in neural tissue engineering. Copyright © 2014 John Wiley & Sons, Ltd.

  1. Platelet activating factor induces dopamine release in PC-12 cell line

    SciTech Connect

    Bussolino, F.; Tessari, F.; Turrini, F.; Braquet, P.; Camussi, G.; Prosdocimi, M.; Bosia, A. Institut Henri Beaufour, Le Plessis Robinson )

    1988-10-01

    The ability of platelet activating factor (PAF) to stimulate dopamine release and modify calcium homeostasis in PC-12 cell line was studied. PAF-induced dopamine release is related to its molecular form, with only the R-form steric configuration ((R)PAF), but not its S-form or its 2-lyso derivative, effective at being active. In addition, PAF acts at very low concentrations in a dose-dependent manner (0.1-30 nM). Preincubation with PAF receptor antagonists (CV-3988 and BN52021) as well as the specific desensitization of PC-12 cells to (R)PAF abolish the (R)PAF-induced dopamine release. Several lines of evidence suggest that dopamine release is dependent on a (R)PAF-induced calcium influx and efflux modulation. Dopamine release by PC-12 cells challenged with (R)PAF is associated with a rapid {sup 45}Ca influx and efflux and a rise in cytoplasmic calcium concentrations ((Ca{sup 2+}){sub i}) evaluated by using the calcium indicators fura-2 and quin2. At 30 nM (R)PAF, the absence of extracellular calcium inhibits the dopamine release but not the rise of (Ca{sup 2+}){sub i} from the internal stores, suggesting the importance of calcium influx in (R)PAF-induced dopamine release. PAF, which has been reported to be synthesized by stimulated neuronal cells may thus have a physiological modulatory role on cells with neurosecretory properties.

  2. Response to histamine allows the functional identification of neuronal progenitors, neurons, astrocytes, and immature cells in subventricular zone cell cultures.

    PubMed

    Agasse, Fabienne; Bernardino, Liliana; Silva, Bruno; Ferreira, Raquel; Grade, Sofia; Malva, João O

    2008-02-01

    Subventricular zone (SVZ) cell cultures contain mixed populations of immature cells, neurons, astrocytes, and progenitors in different stages of development. In the present work, we examined whether cell types of the SVZ could be functionally discriminated on the basis of intracellular free calcium level ([Ca(2+)](i)) variations following KCl and histamine stimulation. For this purpose, [Ca(2+)](i) were measured in SVZ cell cultures from neonatal P1-3 C57Bl/6 donor mice, in single cells, after stimulation with 100 microM histamine or 50 mM KCl. MAP-2-positive neurons and doublecortin-positive neuroblasts were distinguished on the basis of their selective ratio of response to KCl and/or histamine stimulation. Moreover, we could distinguish immature cells on the basis of the selective response to histamine via the histamine 1 receptor activation. Exposure of SVZ cultures to the pro-neurogenic stem cell factor (SCF) induced an increase in the number of cells responding to KCl and a decrease in the number of cells responding to histamine, consistent with neuronal differentiation. The selective response to KCl/histamine in single cell calcium imaging analysis offers a rapid and efficient way for the functional discrimination of neuronal differentiation in SVZ cell cultures, opening new perspectives for the search of potential pro-neurogenic factors.

  3. Study of the biological effectiveness of a nanosilver-epidermal growth factor sustained-release carrier.

    PubMed

    Zhou, Jian-DA; Wang, Shao-Hua; Liu, Rui; Zhou, Chun-Jiao; Cao, Ke; Liu, Jin-Yan; Chen, Yao; Chen, Feng-Hua

    2013-04-01

    The aim of the present study was to elucidate the biological effectiveness and character of a nanosilver-epidermal growth factor (EGF) sustained-release carrier. This was synthesized using the self-assembly method and then characterized by transmission electron microscopy and UV spectrophotometry. The biological activity of the sustained release carrier was determined through cytological, bacteriological and wound-healing experiments. The results showed that the nanosilver-EGF sustained-release carrier was well dispersed with uniform particle size and that it had good antibacterial properties similar to those of nanosilver. The nanosilver-EGF sustained-release carrier is superior to EGFs in effectively promoting cell division and proliferation. The results of the wound-healing experiments provide evidence of its curative effects.

  4. Platelet-rich concentrates differentially release growth factors and induce cell migration in vitro.

    PubMed

    Schär, Michael O; Diaz-Romero, Jose; Kohl, Sandro; Zumstein, Matthias A; Nesic, Dobrila

    2015-05-01

    Platelet-rich concentrates are used as a source of growth factors to improve the healing process. The diverse preparation protocols and the gaps in knowledge of their biological properties complicate the interpretation of clinical results. In this study we aimed to (1) analyze the concentration and kinetics of growth factors released from leukocyte- and platelet-rich fibrin (L-PRF), leukocyte- and platelet-rich plasma (L-PRP), and natural blood clot during in vitro culture; (2) investigate the migration of mesenchymal stem cells (MSCs) and human umbilical vein endothelial cells (HUVECs) as a functional response to the factors released; and (3) uncover correlations between individual growth factors with the initial platelet/leukocyte counts or the induced cell migration. L-PRF, L-PRP, and natural blood clot prepared from 11 donors were cultured in vitro for 28 days and media supernatants collected after 8 hours and 1, 3, 7, 14, and 28 days. Released transforming growth factor β1 (TGF-β1), vascular endothelial growth factor (VEGF), insulin growth factor (IGF-1), platelet-derived growth factor AB (PDGF-AB), and interleukin-1β (IL-1β) were measured in the supernatants with enzyme-linked immunosorbent assay. Migration of MSC and HUVEC induced by the supernatants was evaluated in Boyden chambers. More TGF-ß1 was released (mean ± SD in pg/mL of blood) from L-PRF (37,796 ± 5492) compared with L-PRP (23,738 ± 6848; p < 0.001) and blood clot (3739 ± 4690; p < 0.001), whereas more VEGF and IL-1ß were released from blood clot (1933 ± 704 and 2053 ± 908, respectively) compared with both L-PRP (642 ± 208; p < 0.001 and 273 ± 386; p < 0.001, respectively) and L-PRF (852 ± 376; p < 0.001 and 65 ± 56, p < 0.001, respectively). No differences were observed in IGF-1 and PDGF-AB released from any of the concentrates. TGF-β1 release peaked at Day 7 in L-PRF and at 8 hours and Day 7 in L-PRP and 8 hours and Day 14 in blood clot. In all concentrates, main release of VEGF

  5. Histamine content in sardine and its products.

    PubMed

    Samaha, I A; Elgazzar, M M; El-Atabany, A I

    1997-01-01

    A total of 80 random samples of fresh sardines, salted sardines, locally canned sardines and imported canned sardines (20 from each) were collected from fish markets and shops in Alexandria governorate. The collected samples were analyzed for determination of histamine level by Thin Layer Chromatography. The results revealed that the highest histamine content was observed in locally canned sardines and decreased gradually in salted sardines, imported canned sardines and fresh sardines. The percentages of the examined sardine samples having a higher histamine content than the permissible limit were 5%, 10%, 10% and 5% for fresh, salted, locally canned and imported canned sardines, respectively. The health hazard as well as the suggestive measures for controlling the histamine content in sardine and its products are discussed.

  6. Histamine receptors in the gastric microcirculation.

    PubMed Central

    Guth, P H; Smith, E

    1978-01-01

    The types and functions of histamine receptors in the submucosal arterioles of the corpus and antrum of the cat and rat stomach were studied using an in vivo microscopy technique. Change in arteriolar diameter in response to superfusion of histamine with and without antagonists was measured by an image-splitting technique. H1 and H2 histamine receptors subserving vasodilatation were demonstrated in both the antral and corpus submucosal arterioles of the cat and rat. However, the H1 effect was predominant in the antrum (the H2 antagonist inhibited histamine dilatation only in the presence of the H1 antagonist), while H1 and H2 effects were approximately equal and independent in the corpus. PMID:32123

  7. Modulation of colony stimulating factor release and apoptosis in human colon cancer cells by anticancer drugs

    PubMed Central

    Calatayud, S; Warner, T D; Mitchell, J A

    2002-01-01

    Modulation of the immune response against tumour cells is emerging as a valuable approach for cancer treatment. Some experimental studies have shown that secretion of colony stimulating factors by cancer cells reduces their tumorigenicity and increases their immunogenicity probably by promoting the cytolitic and antigen presenting activities of leukocytes. We have observed that human colon cancer cells (HT-29) are able to secrete granulocyte-macrophage-colony stimulating factor, granulocyte-colony stimulating factor and macrophage-colony stimulating factor when stimulated with cytokines (IL-1β and TNF-α). In this study we assessed, for the first time, the effects of several anticancer drugs on colony stimulating factor release or apoptosis in HT-29 cells. Cytokine-induced release of granulocyte-macrophage-colony stimulating factor, granulocyte-colony stimulating factor and macrophage-colony stimulating factor was significantly increased by cisplatin and 6-mercaptopurine. Taxol only increased macrophage-colony stimulating factor release while reduced that of granulocyte-colony stimulating factor. No changes in colony stimulating factor secretion were observed after treatment with methotrexate. Only cisplatin and taxol induced apoptosis in these cells. Secretion of colony stimulating factors by colon cancer cells may contribute to the immune host response against them. Anticancer drugs such as cisplatin and 6-mercaptopurine increase colony stimulating factor secretion by cytokine stimulated cancer cells probably through mechanisms different to those leading to cell apoptosis, an effect that may contribute to their anti-neoplasic action. British Journal of Cancer (2002) 86, 1316–1321. DOI: 10.1038/sj/bjc/6600240 www.bjcancer.com © 2002 Cancer Research UK PMID:11953891

  8. Mast Cell-Derived Histamine Mediates Cystitis Pain

    PubMed Central

    Rudick, Charles N.; Bryce, Paul J.; Guichelaar, Laura A.; Berry, Ruth E.; Klumpp, David J.

    2008-01-01

    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. PMID:18461160

  9. Exogenous gangliosides increase the release of brain-derived neurotrophic factor.

    PubMed

    Lim, Seung T; Esfahani, Kamilla; Avdoshina, Valeriya; Mocchetti, Italo

    2011-06-01

    Gangliosides are lipophilic compounds found in cell plasma membranes throughout the brain that play a role in neuronal plasticity and regeneration. Indeed, absence or abnormal accumulation of gangliosides has been shown to lead to neurological disorders. Experimental data have shown that exogenous gangliosides exhibit properties similar to the neurotrophins, a family of neurotrophic factors that are important in the survival and maintenance of neurons and prevention of neurological diseases. Brain-derived neurotrophic factor (BDNF) is the most abundant of the neurotrophins. This work was done to reveal the neurotrophic mechanism of exogenous gangliosides. In particular, we examined whether gangliosides promote the release of BDNF. Rat hippocampal neurons or human neuroblastoma cells were transduced with a recombinant adenovirus expressing BDNF-flag to facilitate detection of BDNF. Release of BDNF was then determined by Western blot analysis and a two-site immunoassay of culture medium. The depolarizing agent KCl was used as a comparison. In hippocampal neurons, both GM1 ganglioside and KCl evoked within minutes the release of mature BDNF. In human cells, GM1 and other gangliosides released both mature BDNF and pro-BDNF. The effect of gangliosides was structure-dependent. In fact, GT1b preferentially released mature BDNF whereas GM1 released both mature and pro-BDNF. Ceramide and sphingosine did not modify the release of BDNF. This work provides additional experimental evidence that exogenous gangliosides can be used to enhance the neurotrophic factor environment and promote neuronal survival in neurological diseases. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'. Copyright © 2010 Elsevier Ltd. All rights reserved.

  10. Structure of the human histamine H1 receptor gene.

    PubMed Central

    De Backer, M D; Loonen, I; Verhasselt, P; Neefs, J M; Luyten, W H

    1998-01-01

    Histamine H1 receptor expression has been reported to change in disorders such as allergic rhinitis, autoimmune myocarditis, rheumatoid arthritis and atherosclerosis. Here we report the isolation and characterization of genomic clones containing the 5' flanking (regulatory) region of the human histamine H1 receptor gene. An intron of approx. 5.8 kb was identified in the 5' untranslated region, which suggests that an entire subfamily of G-protein-coupled receptors may contain an intron immediately upstream of the start codon. The transcription initiation site was mapped by 5' rapid amplification of cDNA ends to a region 6.2 kb upstream of the start codon. Immediately upstream of the transcription start site a fragment of 1.85 kb was identified that showed promoter activity when placed upstream of a luciferase reporter gene and transiently transfected into cells expressing the histamine H1 receptor. The promoter sequence shares a number of characteristics with the promoter sequences of other G-protein-coupled receptor encoding genes, including binding sites for several transcription factors, and the absence of TATA and CAAT sequences at the appropriate locations. The promoter sequence described here differs from that reported previously [Fukui, Fujimoto, Mizuguchi, Sakamoto, Horio, Takai, Yamada and Ito (1994) Biochem. Biophys. Res. Commun. 201, 894-901] because the reported genomic clone was chimaeric. Furthermore our study provides evidence that the 3' untranslated region of the H1 receptor mRNA is much longer than previously accepted. Together, these findings provide a complete view of the structure of the human histamine H1 receptor gene. Both the coding region of the H1 receptor gene and its promoter region were independently mapped to chromosome 3p25. PMID:9794809

  11. A primary role for release factor 3 in quality control during translation elongation in Escherichia coli.

    PubMed

    Zaher, Hani S; Green, Rachel

    2011-10-14

    Release factor 3 (RF3) is a GTPase found in a broad range of bacteria where it is thought to play a critical "recycling" role in translation by facilitating the removal of class 1 release factors (RF1 and RF2) from the ribosome following peptide release. More recently, RF3 was shown in vitro to stimulate a retrospective editing reaction on the bacterial ribosome wherein peptides carrying mistakes are prematurely terminated during protein synthesis. Here, we examine the role of RF3 in the bacterial cell and show that the deletion of this gene sensitizes cells to other perturbations that reduce the overall fidelity of protein synthesis. We further document substantial effects on mRNA stability and protein expression using reporter systems, native mRNAs and proteins. We conclude that RF3 plays a primary role in vivo in specifying the fidelity of protein synthesis thus impacting overall protein quantity and quality.

  12. Luteinizing hormone releasing factor in rat hypophysial portal blood collected during electrical stimulation of the hypothalamus

    PubMed Central

    Harris, G. W.; Ruf, K. B.

    1970-01-01

    1. Ovulation was induced in Nembutal-blocked pro-oestrous rats by electrical stimulation of the hypothalamus. 2. The same type of electrical stimulation was applied during the collection of hypophysial portal blood. 3. Pooled hypophysial portal plasma from donors in pro-oestrus, oestrus and met-oestrus was assayed for ovarian ascorbic acid depleting (OAAD) activity. 4. Electrical stimulation of the hypothalamus increased the OAAD activity, believed to be due to luteinizing hormone releasing factor (LRF), in pro-oestrus and met-oestrus, but not in oestrus. 5. It is concluded that the hypothalamic nerve fibres responsible for releasing LRF into the hypophysial portal vessels are depleted of their store of this releasing factor, or are refractory to electrical stimulation, during oestrus. PMID:5499765

  13. Inhaled histamine increases human lung mucociliary transport

    SciTech Connect

    Mussatto, D.J.; Garrard, C.S.; Trumbull, J.J.; Bowers, M.W.; Sanders, C.J.; Yeates, D.B.; Lourenco, R.V.

    1986-03-01

    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 FEV/sub 1/ was established for each subject. On a separate day the subjects inhaled a 9 ..mu..m MMAD /sup 99m/Tc-Fe/sub 2/O/sub 3/ 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 Fe/sub 2/O/sub 3/ retained after 24h for histamine (14.4 +/- 7.6%) and PBS studies (13.1 +/- 8.6%) indicated no difference in deposition of Fe/sub 2/O/sub 3/ (ANOVA). Fe/sub 2/O/sub 3/ 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. Diamine Oxidase from White Pea (Lathyrus sativus) Combined with Catalase Protects the Human Intestinal Caco-2 Cell Line from Histamine Damage.

    PubMed

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

    2017-01-20

    Diamine oxidase (DAO) administration has been proposed to treat certain gastrointestinal dysfunctions induced by histamine, an immunomodulator, signaling, and pro-inflammatory factor. However, H2O2 resulting from the oxidative deamination of histamine by DAO may be toxic. The purpose of this study was to investigate to which extent DAO from white pea (Lathyrus sativus), alone or in combination with catalase, may modulate histamine toxicity in the human intestinal Caco-2 cell line. The results show that histamine at concentrations higher than 1 mM is toxic to the Caco-2 cells, independently of the cell differentiation status, with a LC50 of ≅ 10 mM following a 24-h exposure. Depending on its concentration, DAO increased histamine toxicity to a greater extent in differentiated cells compared to undifferentiated cultures. In the presence of catalase, the DAO-induced increase in histamine toxicity was completely abolished in the undifferentiated cells and only partially decreased in differentiated cells, showing differences in the sensitivity of Caco-2 cells to the products resulting from histamine degradation by DAO (H2O2, NH3, or imidazole aldehyde). It appears that treatment of food histaminosis using a combination of vegetal DAO and catalase would protect against histamine toxicity and prevent H2O2-induced damage that may occur during histamine oxidative deamination.

  15. Proton nuclear magnetic resonance studies of mast cell histamine

    SciTech Connect

    Rabenstein, D.L.; Ludowyke, R.; Lagunoff, D.

    1987-11-03

    The state of histamine in mast cells was studied by /sup 1/H NMR spectroscopy. Spectra were measured for histamine in situ in intact mast cells, for histamine in suspensions of mast cell granule matrices that had been stripped of their membranes, and for histamine in solutions of heparin. The /sup 1/H NMR spectrum of intact mast cells is relatively simple, consisting predominantly of resonances for intracellular histamine superimposed on a weaker background of resonances from heparin and proteins of the cells. All of the intracellular histamine contributes of the NMR signals, indicating it must be relatively mobile and not rigidly associated with the negatively charged granule matrix. Spectra for intracellular histamine and for histamine in granule matrices are similar, indicating the latter to be a reasonable model for the in situ situation. The dynamics of binding of histamine by granule matrices and by heparin are considerably different; exchange of histamine between the bulk water and the granule matrices is slow on the /sup 1/H NMR time scale, whereas exchange between the free and bound forms in heparin solution is fast. The chemical shifts of resonances for histamine in mast cells are pH dependent, decreasing as the intragranule pH increases without splitting or broadening. The results are interpreted to indicate that histamine in mast cells is relatively labile, with rapid exchange between histamine and pools of free histamine in water compartments confined in the granule matrix.

  16. Histamine derived from probiotic Lactobacillus reuteri suppresses TNF via modulation of PKA and ERK signaling.

    PubMed

    Thomas, Carissa M; Hong, Teresa; van Pijkeren, Jan Peter; Hemarajata, Peera; Trinh, Dan V; Hu, Weidong; Britton, Robert A; Kalkum, Markus; Versalovic, James

    2012-01-01

    Beneficial microbes and probiotic species, such as Lactobacillus reuteri, produce biologically active compounds that can modulate host mucosal immunity. Previously, immunomodulatory factors secreted by L. reuteri ATCC PTA 6475 were unknown. A combined metabolomics and bacterial genetics strategy was utilized to identify small compound(s) produced by L. reuteri that were TNF-inhibitory. Hydrophilic interaction liquid chromatography-high performance liquid chromatography (HILIC-HPLC) separation isolated TNF-inhibitory compounds, and HILIC-HPLC fraction composition was determined by NMR and mass spectrometry analyses. Histamine was identified and quantified in TNF-inhibitory HILIC-HPLC fractions. Histamine is produced from L-histidine via histidine decarboxylase by some fermentative bacteria including lactobacilli. Targeted mutagenesis of each gene present in the histidine decarboxylase gene cluster in L. reuteri 6475 demonstrated the involvement of histidine decarboxylase pyruvoyl type A (hdcA), histidine/histamine antiporter (hdcP), and hdcB in production of the TNF-inhibitory factor. The mechanism of TNF inhibition by L. reuteri-derived histamine was investigated using Toll-like receptor 2 (TLR2)-activated human monocytoid cells. Bacterial histamine suppressed TNF production via activation of the H(2) receptor. Histamine from L. reuteri 6475 stimulated increased levels of cAMP, which inhibited downstream MEK/ERK MAPK signaling via protein kinase A (PKA) and resulted in suppression of TNF production by transcriptional regulation. In summary, a component of the gut microbiome, L. reuteri, is able to convert a dietary component, L-histidine, into an immunoregulatory signal, histamine, which suppresses pro-inflammatory TNF production. The identification of bacterial bioactive metabolites and their corresponding mechanisms of action with respect to immunomodulation may lead to improved anti-inflammatory strategies for chronic immune-mediated diseases.

  17. Recombinant gamma interferon causes neutrophil migration mediated by the release of a macrophage neutrophil chemotactic factor.

    PubMed Central

    Ribeiro, R. A.; Cunha, F. Q.; Ferreira, S. H.

    1990-01-01

    A dose-dependent neutrophil migration was observed following the injection of purified (Hu IFN-gamma) or recombinant (rIFN-gamma) human gamma interferon into rat peritoneal cavities. This finding contrasts with their inability to cause chemotaxis in vitro in the Boyden chamber. Neutrophil migration into peritoneal cavities and subcutaneous air pouches induced by both preparations of interferon was abolished by pretreatment of the animals with dexamethasone. IFN-gamma-induced neutrophil migration was enhanced when the macrophage population of the peritoneal cavities was increased by previous injection of thioglycollate and reduced by peritoneal lavage. Macrophage monolayers pretreated either with rIFN-gamma or with lipopolysaccharide from E. coli release into the supernatant a factor that stimulates neutrophil recruitment in animals treated with dexamethasone. Dexamethasone blocked this release but did not affect the neutrophil recruitment induced by this factor. These results suggest that IFN-gamma-induced neutrophil migration in vivo may be mediated by the release from resident macrophages of a neutrophil chemotactic factor and that dexamethasone blockade of neutrophil recruitment by IFN-gamma is due to inhibition of the release of this factor. PMID:2119790

  18. The purification of luteinizing-hormone-releasing factor with some observations on its properties

    PubMed Central

    Fawcett, C. P.; Reed, May; Charlton, H. M.; Harris, G. W.

    1968-01-01

    Bullock median-eminence tissue was used as a source of luteinizing-hormone-releasing factor for small-scale experiments to explore methods for its isolation. The presence of luteinizing-hormone-releasing factor was detected by the ovulation response in rabbits after intrapituitary infusion of the extract. Gel filtration was found to be suitable for the purification of these extracts. The releasing factor appeared to be a basic peptide of molecular weight in the range 1200–2500. On a larger scale, an extract of hypothalamic tissue from sheep was used to establish a multi-stage isolation procedure that resulted in a 200000-fold purification of luteinizing-hormone-releasing factor. After the initial extraction the isolation process consisted of: (1) two cycles of gel filtration; (2) anion-exchange chromatography; (3) gel filtration in a partially organic medium; (4) thin-layer chromatography on cellulose. Stage (3) separated two zones of activity each containing peptides. One of these was purified further by stage (4) to give a preparation that was active at a dose of 6μg. of peptide/animal, although activity diminished seriously during storage. This preparation contained only five or six components, but the small amounts of peptides obtained at this stage of purity were insufficient for full characterization. ImagesFig. 5. PMID:4889362

  19. Ethanol and Corticotropin Releasing Factor Receptor Modulation of Central Amygdala Neurocircuitry: an Update and Future Directions

    PubMed Central

    Silberman, Yuval; Winder, Danny G.

    2015-01-01

    The central amygdala is a critical brain region for many aspects of alcohol dependence. Much of the work examining the mechanisms by which the central amygdala mediates the development of alcohol dependence has focused on the interaction of acute and chronic ethanol with central amygdala corticotropin releasing factor signaling. This work has led to a great deal of success in furthering the general understanding of central amygdala neurocircuitry and its role in alcohol dependence. Much of this work has primarily focused on the hypothesis that ethanol utilizes endogenous corticotropin releasing factor signaling to upregulate inhibitory GABAergic transmission in the central amygdala. Work that is more recent suggests that corticotropin releasing factor also plays an important role in mediating anxiety-like behaviors via the enhancement of central amygdala glutamatergic transmission, implying that ethanol/corticotropin releasing factor interactions may modulate excitatory neurotransmission in this brain region. In addition, a number of studies utilizing optogenetic strategies or transgenic mouse lines have begun to examine specific central amygdala neurocircuit dynamics and neuronal subpopulations to better understand overall central amygdala neurocircuitry and the role of neuronal subtypes in mediating anxiety-like behaviors. This review will provide a brief update on this literature and describe some potential future directions that may be important for the development of better treatments for alcohol addiction. PMID:25716197

  20. Ethanol and corticotropin releasing factor receptor modulation of central amygdala neurocircuitry: An update and future directions.

    PubMed

    Silberman, Yuval; Winder, Danny G

    2015-05-01

    The central amygdala is a critical brain region for many aspects of alcohol dependence. Much of the work examining the mechanisms by which the central amygdala mediates the development of alcohol dependence has focused on the interaction of acute and chronic ethanol with central amygdala corticotropin releasing factor signaling. This work has led to a great deal of success in furthering the general understanding of central amygdala neurocircuitry and its role in alcohol dependence. Much of this work has primarily focused on the hypothesis that ethanol utilizes endogenous corticotropin releasing factor signaling to upregulate inhibitory GABAergic transmission in the central amygdala. Work that is more recent suggests that corticotropin releasing factor also plays an important role in mediating anxiety-like behaviors via the enhancement of central amygdala glutamatergic transmission, implying that ethanol/corticotropin releasing factor interactions may modulate excitatory neurotransmission in this brain region. In addition, a number of studies utilizing optogenetic strategies or transgenic mouse lines have begun to examine specific central amygdala neurocircuit dynamics and neuronal subpopulations to better understand overall central amygdala neurocircuitry and the role of neuronal subtypes in mediating anxiety-like behaviors. This review will provide a brief update on this literature and describe some potential future directions that may be important for the development of better treatments for alcohol addiction.

  1. 77 FR 4227 - Implantation or Injectable Dosage Form New Animal Drugs; Gonadotropin Releasing Factor Analog...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-27

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 522 Implantation or Injectable Dosage Form New... gonadotropin releasing factor analog-diphtheria toxoid conjugate injectable solution. DATES: This rule is...: PART 522--IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS 0 1. The authority citation for...

  2. Effect of growth hormone-releasing factor on growth hormone release in children with radiation-induced growth hormone deficiency

    SciTech Connect

    Lustig, R.H.; Schriock, E.A.; Kaplan, S.L.; Grumbach, M.M.

    1985-08-01

    Five male children who received cranial irradiation for extrahypothalamic intracranial neoplasms or leukemia and subsequently developed severe growth hormone (GH) deficiency were challenged with synthetic growth hormone-releasing factor (GRF-44), in an attempt to distinguish hypothalamic from pituitary dysfunction as a cause of their GH deficiency, and to assess the readily releasable GH reserve in the pituitary. In response to a pulse of GRF-44 (5 micrograms/kg intravenously), mean peak GH levels rose to values higher than those evoked by the pharmacologic agents L-dopa or arginine (6.4 +/- 1.3 ng/mL v 1.5 +/- 0.4 ng/mL, P less than .05). The peak GH value occurred at a mean of 26.0 minutes after administration of GRF-44. These responses were similar to those obtained in children with severe GH deficiency due to other etiologies (peak GH 6.3 +/- 1.7 ng/mL, mean 28.0 minutes). In addition, there was a trend toward an inverse relationship between peak GH response to GRF-44 and the postirradiation interval. Prolactin and somatomedin-C levels did not change significantly after the administration of a single dose of GRF-44. The results of this study support the hypothesis that cranial irradiation in children can lead to hypothalamic GRF deficiency secondary to radiation injury of hypothalamic GRF-secreting neurons. This study also lends support to the potential therapeutic usefulness of GRF-44 or an analog for GH deficiency secondary to cranial irradiation.

  3. Effect of antidepressants on brain-derived neurotrophic factor (BDNF) release from platelets in the rats.

    PubMed

    Watanabe, Kimihiko; Hashimoto, Eri; Ukai, Wataru; Ishii, Takao; Yoshinaga, Toshihiro; Ono, Takafumi; Tateno, Masaru; Watanabe, Ippei; Shirasaka, Tomohiro; Saito, Satoshi; Saito, Toshikazu

    2010-12-01

    Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family, and enhances the growth and maintenance of several neuronal systems. In addition, BDNF may promote neurogenesis and protect against hippocampal volume loss in depressive disorders. Although first detected in brain, BDNF also exists in peripheral tissues and is mainly stored in platelets and circulates in blood. Recent reports indicate that serum BDNF levels in depressive patients are lower than in control subjects, and antidepressant treatment increases serum BDNF levels in responders. A single report suggests that decreased serum BDNF in major depression is related to mechanisms of platelet BDNF release; however, the mechanisms of changes in BDNF blood levels are still poorly understood. In the present study, we investigated the direct influence of antidepressants on BDNF release from platelets and their effects on serum levels. We used samples of washed platelets prepared from rat blood, and investigated the platelet BDNF release and serum BDNF concentration changes in response to adding antidepressants. We found that BDNF was dose-dependently released from platelets by direct treatment with various kinds of antidepressants in vitro, and serum BDNF concentration was also increased by intravenous antidepressant treatment. These results confirm that BDNF release from platelets is affected by antidepressants, which may relate to the circulating BDNF level change in peripheral blood. The response of BDNF release differs depending on the type and amount of antidepressants, making BDNF a serious candidate as a predictor of antidepressant treatment response. Copyright © 2010 Elsevier Inc. All rights reserved.

  4. Neutrophil chemotactic factor release and neutrophil alveolitis in asbestos-exposed individuals

    SciTech Connect

    Hayes, A.A.; Rose, A.H.; Musk, A.W.; Robinson, B.W.

    1988-09-01

    Alveolar neutrophil accumulation occurs in asbestosis. To evaluate a possible role for release of neutrophil chemotactic factor (NCF) in the pathogenesis of asbestosis, spontaneous NCF release from alveolar macrophages obtained by bronchoalveolar lavage (BAL) in eight individuals with asbestosis, 13 asbestos-exposed individuals without asbestosis, and five control subjects has been studied. Alveolar macrophages were incubated in medium (four hours; 37 degrees C), and neutrophil responses to the supernatants were assayed in a microchemotaxis chamber. Alveolar macrophages from subjects with asbestosis released more NCF (97 +/- 19 neutrophils per high-power field (N/HPF)) than controls (3 +/- 1 N/HPF; p less than 0.01). Alveolar macrophages from individuals with asbestos exposure and increased BAL neutrophil proportions (n = 7) released more NCF (93 +/- 24 N/HPF) than individuals with asbestos exposure and normal BAL neutrophil proportions (n = 6; 11 +/- 6 N/HPF; p less than 0.02). The results show that spontaneous NCF release occurs in asbestosis and that NCF release is associated with neutrophil alveolitis in asbestos-exposed individuals without asbestosis, suggesting a pathogenic role for NCF in mediating this neutrophil alveolitis. The results of the study also suggest that the presence of crackles is a better predictor of the presence of neutrophil alveolitis than is an abnormal chest x-ray film.

  5. Release kinetics of platelet-derived and plasma-derived growth factors from autologous plasma rich in growth factors.

    PubMed

    Anitua, Eduardo; Zalduendo, Mari Mar; Alkhraisat, Mohammad Hamdan; Orive, Gorka

    2013-10-01

    Many studies have evaluated the biological effects of platelet rich plasma reporting the final outcomes on cell and tissues. However, few studies have dealt with the kinetics of growth factor delivery by plasma rich in growth factors. Venous blood was obtained from three healthy volunteers and processed with PRGF-Endoret technology to prepare autologous plasma rich in growth factors. The gel-like fibrin scaffolds were then incubated in triplicate, in a cell culture medium to monitor the release of PDGF-AB, VEGF, HGF and IGF-I during 8 days of incubation. A leukocyte-platelet rich plasma was prepared employing the same technology and the concentrations of growth factors and interleukin-1β were determined after 24h of incubation. After each period, the medium was collected, fibrin clot was destroyed and the supernatants were stored at -80°C until analysis. The growth factor delivery is diffusion controlled with a rapid initial release by 30% of the bioactive content after 1h of incubation and a steady state release when almost 70% of the growth factor content has been delivered. Autologous fibrin matrix retained almost 30% of the amount of the growth factors after 8 days of incubation. The addition of leukocytes to the formula of platelet rich plasma did not increase the concentration of the growth factors, while it drastically increased the presence of pro-inflammatory IL-1β. Further studies employing an in vitro inflammatory model would be interesting to study the difference in growth factors and pro-inflammatory cytokines between leukocyte-free and leukocyte-rich platelet rich plasma.

  6. Physiological factors of atrial natriuretic polypeptide release and its neural regulation in conscious dogs.

    PubMed

    Nishida, Y; Miyata, A; Morita, H; Hosomi, H

    1988-12-01

    We have examined physiological factors in atrial natriuretic polypeptide (ANP) release and whether or not the cardiac nerves control release of ANP. Two possible factors were tested, an increase in plasma sodium level (PNa) and an increase in atrial pressure. Injection of 1.0 or 2.0 mEq/kg of sodium ions elevated PNa by 5.3 +/- 0.3 or 7.3 +/- 0.4 mEq/L, respectively, but plasma ANP level (PANP) did not change. Infusion of 18 ml/kg of 3% Dextran-40 over 5 min increased mean left atrial pressure (MLAP) by 7.6 +/- 0.9 mmHg. PANP increased from 206 +/- 17 pg/ml to 260 +/- 25 pg/ml, which was not significant. PANP, corrected for hemodilution, significantly increased to 348 +/- 34 pg/ml. These results suggest that PNa increase does not promote ANP release, but that an atrial pressure increase does. This transient volume load did not induce full response of the ANP releasing system. A prolonged volume load for 45 min increased corrected PANP to 435 +/- 73 pg/ml. A close linear correlation was found between the increases in MLAP and PANP. These facts indicate that prolonged volume expansion is necessary to induce full response of the ANP releasing system. Complete cardiac denervation did not affect the tonic level of plasma ANP, volume expansion-induced increase in PANP, or the sensitivity of the ANP releasing system. Thus we conclude that the cardiac nerves do not control ANP release caused by volume expansion.

  7. Mineral coatings modulate β-TCP stability and enable growth factor binding and release.

    PubMed

    Suárez-González, Darilis; Lee, Jae Sung; Lan Levengood, Sheeny K; Vanderby, Ray; Murphy, William L

    2012-03-01

    β-Tricalcium phosphate (β-TCP) is an attractive ceramic for bone tissue repair because of its similar composition to bone mineral and its osteoconductivity. However, compared with other ceramics β-TCP has a rapid and uncontrolled rate of degradation. In the current study β-TCP granules were mineral coated with the aim of influencing the dissolution rate of β-TCP, and also to use the coating as a carrier for controlled release of the growth factors recombinant human vascular endothelial growth factor (rhVEGF), modular VEGF peptide (mVEGF), and modular bone morphogenetic protein 2 peptide (mBMP2). The biomineral coatings were formed by heterogeneous nucleation in aqueous solution using simulated body fluid solutions with varying concentrations of bicarbonate (HCO(3)). Our results demonstrate that we could coat β-TCP granules with mineral layers possessing different dissolution properties. The presence of a biomineral coating delays the dissolution rate of the β-TCP granules. As the carbonate (CO(3)(2-)) content in the coating was increased the dissolution rate of the coated β-TCP also increased, but remained slower than the dissolution of uncoated β-TCP. In addition, we showed sustained release of multiple growth factors, with release kinetics that were controllable by varying the identity of the growth factor or the CO(3)(2-) content in the mineral coating. Released rhVEGF induced human umbilical vein endothelial cell (HUVEC) proliferation, and mVEGF enhanced migration of mouse embryonic endothelial cells in a scratch wound healing assay, indicating that each released growth factor was biologically active.

  8. Effect of carnosine on the immunosuppressive effect of histamine

    SciTech Connect

    Sharpan, Yu. V.

    1985-04-01

    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.

  9. The effect of enzyme inhibitors on histamine catabolism in man

    PubMed Central

    Lindell, S. E.; Nilsson, Karen; Roos, B.-E.; Westling, H.

    1960-01-01

    The catabolism of histamine was studied in three female psychiatric patients by analysis of the [14C]-labelled metabolic products occurring in the urine after a subcutaneous injection of [14C]histamine. Each patient was studied before and during treatment with aminoguanidine or iproniazid. Without treatment the patients had a normal histamine catabolism. Aminoguanidine and iproniazid inhibited the oxidation of histamine to imidazoleacetic acid; iproniazid produed a 50% inhibition of the oxidation of methylhistamine to methylimidazoleacetic acid. After iproniazid a large proportion of the injected [C14]histamine was excreted as methyl [14C]histamine. PMID:14417081

  10. [Effect of alahistidine on brain histamine content and seizure development].

    PubMed

    Hu, Wei-wei; Chen, Zhong; Xu, Li-sha; Jin, Chun-lei; Sakurai, Eiko; Yanai, Kazuhiko

    2004-05-01

    To investigate the effect of alahistidine on brain histamine content and seizure development. The kindling seizure was induced by ip injection with subconvulsant dose of pentylenetetrazole every 48 h. Monoamines and their metabolites were measured using a HPLC system and fluorometric assay. Chronic low histamine feeding markedly decreased histamine content in cortex and hypothalamus, and promoted seizure development induced by pentylenetetrazole. However, alahistidine feed reversed the decreased histamine content and slowed seizure development caused by low histamine feed. Both low histamine and alahistidine feed had no effect on norepinephrine, dopamine and its metabolites. Alahistidine may affect histaminergic system and seizure development.

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

    PubMed

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

    2006-07-01

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

  12. Determination of histamine in microdialysis samples from rat brain by microbore column liquid chromatography following intramolecular excimer-forming derivatization with pyrene-labeling reagent.

    PubMed

    Yoshitake, Takashi; Yamaguchi, Masatoshi; Nohta, Hitoshi; Ichinose, Fumio; Yoshida, Hideyuki; Yoshitake, Shimako; Fuxe, Kjell; Kehr, Jan

    2003-07-15

    This paper describes a sensitive and selective liquid chromatographic method with fluorescence detection for determination of histamine in brain microdialysis samples from awake rats. Samples containing histamine (10 microl) were derivatized with 20 microl of the reagent consisting of 3 mM 4-(1-pyrene)butyric acid N-hydroxysuccinimide ester (PSE), 3 mM potassium carbonate and acetonitrile (1:1:18, v/v), thereafter 20 microl volume was injected onto the microbore column packed with C18 silica gel. The histamine derivative contained two pyrene moieties, which generated intramolecular excimer fluorescence (450-540 nm) and allowed clear discrimination from the monomer fluorescence (360-420 nm) emitted by PSE itself. The separation of histamine-pyrene derivative was achieved within 25 min, the detection limit (S/N=3) was 0.3 fmol histamine in 20 microl injected. The basal extracellular levels of histamine collected in 10-min fractions (fmol per 10 microl, mean+/-S.D., not corrected for recovery, n=10 rats) were 35.45+/-4.56 (hypothalamus), 9.05+/-1.56 (prefrontal cortex), 7.83+/-0.86 (hippocampus) and 6.54+/-0.66 (striatum). The voltage-sensitive release of histamine was evaluated by perfusing the probes with high (100 mM) concentration of potassium ions or with sodium channel blocker tetrodotoxin (1 microM), and the calcium-dependent release was tested by perfusion with calcium-free Ringer solution. These data, together with physiologically induced increase of extracellular histamine in four examined brain regions during forced swimming demonstrate that this method is suitable for high-sensitive determination of neuronally released histamine under various pharmacological and physiological conditions.

  13. Mast Cell Proteases 6 and 7 Stimulate Angiogenesis by Inducing Endothelial Cells to Release Angiogenic Factors

    PubMed Central

    de Souza, Devandir Antonio; Borges, Antonio Carlos; Santana, Ana Carolina; Oliver, Constance; Jamur, Maria Célia

    2015-01-01

    Mast cell proteases are thought to be involved with tumor progression and neo-vascularization. However, their exact role is still unclear. The present study was undertaken to further elucidate the function of specific subtypes of recombinant mouse mast cell proteases (rmMCP-6 and 7) in neo-vascularization. SVEC4-10 cells were cultured on Geltrex® with either rmMCP-6 or 7 and tube formation was analyzed by fluorescence microscopy and scanning electron microscopy. Additionally, the capacity of these proteases to induce the release of angiogenic factors and pro and anti-angiogenic proteins was analyzed. Both rmMCP-6 and 7 were able to stimulate tube formation. Scanning electron microscopy showed that incubation with the proteases induced SVEC4-10 cells to invade the gel matrix. However, the expression and activity of metalloproteases were not altered by incubation with the mast cell proteases. Furthermore, rmMCP-6 and rmMCP-7 were able to induce the differential release of angiogenic factors from the SVEC4-10 cells. rmMCP-7 was more efficient in stimulating tube formation and release of angiogenic factors than rmMCP-6. These results suggest that the subtypes of proteases released by mast cells may influence endothelial cells during in vivo neo-vascularization. PMID:26633538

  14. Silk fibroin matrices for the controlled release of nerve growth factor (NGF).

    PubMed

    Uebersax, Lorenz; Mattotti, Marta; Papaloïzos, Michaël; Merkle, Hans P; Gander, Bruno; Meinel, Lorenz

    2007-10-01

    Nerve conduits (NC) for peripheral nerve repair should guide the sprouting axons and physically protect the axonal cone from any damage. The NC should also degrade after completion of its function to obviate the need of subsequent explanation and should optionally be suitable for controlled drug release of embedded growth factors to enhance nerve regeneration. Silk fibroin (SF) is a biocompatible and slowly biodegradable biomaterial with excellent mechanical properties that could meet the above stated requirements. SF material (films) supported the adherence and metabolic activity of PC12 cells, and, in combination with nerve growth factor (NGF), supported neurite outgrowth during PC12 cell differentiation. NGF-loaded SF-NC were prepared from aqueous solutions of NGF and SF (20%, w/w), which were air-dried or freeze-dried (freezing at -20 or -196 degrees C) in suitable molds. NGF release from the three differently prepared SF-NC was prolonged over at least 3 weeks, but the total amount released depended on the drying procedure of the NC. The potency of released NGF was retained within all formulations. Control experiments with differently dried NGF-lactose solutions did not evidence marked protein aggregation (SEC, HPLC), loss of ELISA-reactivity or PC12 cell bioactivity. This study encourages the further exploitation of SF-NC for growth factor delivery and evaluation in peripheral nerve repair.

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

    PubMed

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

    2013-01-01

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

  16. Isolation and characterization of lipid-protein particles containing platelet factor 3 released from human platelets.

    PubMed Central

    Sandberg, H; Andersson, L O; Höglund, S

    1982-01-01

    Lipid-protein particles with platelet factor 3 measured by the Stypven clotting-time test [Hardisty & Hutton (1966) Br. J. Haematol. 12, 764-776] have been isolated from platelet-release supernatant. Starting material was washed platelets, which were released by treatment with collagen. Purification of the particles from other components in the release material was accomplished by gel filtration on Sepharose CL-4B followed by affinity chromatography on poly-L-lysine-Sepharose CL-4B gel. Chemical characterization showed that the particles were composed of 40% protein, 42% phospholipids, 13% cholesterol and 5% triacylglycerols. The phospholipid composition was 38% phosphatidylcholine, 25% phosphatidylethanolamine, 9% phosphatidylserine, 2% phosphatidic acid and 26% sphingomyelin. No carbohydrate was detected. Electron-microscopic studies revealed the presence of membranous particles with diameters between 70 and 170 nm. Images PLATE 1 Fig. 3. PMID:7103943

  17. Brain derived neurotrophic factor release from layer-by-layer coated agarose nerve guidance scaffolds.

    PubMed

    Lynam, Daniel A; Shahriari, Dena; Wolf, Kayla J; Angart, Phillip A; Koffler, Jacob; Tuszynski, Mark H; Chan, Christina; Walton, Patrick; Sakamoto, Jeffrey

    2015-05-01

    Agarose nerve guidance scaffolds (NGS) seeded with cells expressing brain derived neurotrophic factor (BDNF) have demonstrated robust nerve regeneration in the rat central nervous system. The purpose of this work was to explore whether agarose NGS coated with hydrogen-bonded layer-by-layer (HLbL) could provide an acellular method of delivering prolonged and consistent dosages of active BDNF. Our results show that HLbL-coated agarose NGS could release BDNF over 10days in consistent dosages averaging 80.5±12.5(SD)ng/mL. Moreover, the BDNF released from HLbL was confirmed active by in vitro cell proliferation assays. To our knowledge, this is the first report demonstrating that HLbL assembled onto a hydrogel can provide consistent, prolonged release of active BDNF in clinically relevant dosages.

  18. Histamine and Immune Biomarkers in CNS Disorders

    PubMed Central

    Cacabelos, Ramón; Torrellas, Clara; Fernández-Novoa, Lucía; López-Muñoz, Francisco

    2016-01-01

    Neuroimmune dysregulation is a common phenomenon in different forms of central nervous system (CNS) disorders. Cross-links between central and peripheral immune mechanisms appear to be disrupted as reflected by a series of immune markers (CD3, CD4, CD7, HLA-DR, CD25, CD28, and CD56) which show variability in brain disorders such as anxiety, depression, psychosis, stroke, Alzheimer's disease, Parkinson's disease, attention-deficit hyperactivity disorder, migraine, epilepsy, vascular dementia, mental retardation, cerebrovascular encephalopathy, multiple sclerosis, brain tumors, cranial nerve neuropathies, mental retardation, and posttraumatic brain injury. Histamine (HA) is a pleiotropic monoamine involved in several neurophysiological functions, neuroimmune regulation, and CNS pathogenesis. Changes in brain HA show an age- and sex-related pattern, and alterations in brain HA levels are present in different CNS regions of patients with Alzheimer's disease (AD). Brain HA in neuronal and nonneuronal compartments plays a dual role (neurotrophic versus neurotoxic) in a tissue-specific manner. Pathogenic mechanisms associated with neuroimmune dysregulation in AD involve HA, interleukin-1β, and TNF-α, whose aberrant expression contributes to neuroinflammation as an aggravating factor for neurodegeneration and premature neuronal death. PMID:27190492

  19. Membrane-bound transcription factors: regulated release by RIP or RUP.

    PubMed

    Hoppe, T; Rape, M; Jentsch, S

    2001-06-01

    Regulated nuclear transport of transcription factors from cytoplasmic pools is a major route by which eukaryotes control gene expression. Exquisite examples are transcription factors that are kept in a dormant state in the cytosol by membrane anchors; such proteins are released from membranes by proteolytic cleavage, which enables these transcription factors to enter the nucleus. Cleavage can be mediated either by regulated intramembrane proteolysis (RIP) catalysed by specific membrane-bound proteases or by regulated ubiquitin/proteasome-dependent processing (RUP). In both cases processing can be controlled by cues that originate at or in the vicinity of the membrane.

  20. Improved survival from compound 48/80-induced lethal stress and inhibition of myocardial histamine and carnosine mobilization by lodoxamide.

    PubMed

    Flancbaum, L; Fitzpatrick, J C; Fisher, H

    1989-02-01

    The precise roles of carnosine and histamine in the physiologic response of the cardiovascular system to stress are unknown. We have previously shown in skeletal and cardiac muscle that carnosine serves as a histidine reservoir available for subsequent histamine synthesis following trauma and sepsis. This study was designed to quantify the effect of histamine-releasing and blocking agents on the myocardial carnosine-histamine pathway as well as on survival during severe stress. Four groups of mature (9-month-old) Sprague-Dawley rats were treated with either (1) saline, (2) lodoxamide (L, mast cell degranulation inhibitor), (3) compound 48/80 (a mast cell degranulator which causes stress), or (4) L followed by 48/80, and observed until agonal or the end of 30 min. When either endpoint was reached the animals were sacrificed and their hearts were removed for tissue analyses of histidine, histamine, 3-methylhistamine, and carnosine via high-pressure liquid chromatography. All five L-pretreated animals survived challenge with 48/80 while all five animals given 48/80 alone died (P less than .005). This mortality correlated well with the increase in the myocardial levels of histidine (P less than or equal to .0005), histamine (P less than or equal to .0077), and 3-methylhistamine (P less than or equal to .0004) and the decrease in carnosine (P less than or equal to .009) experienced by the animals treated with 48/80 alone in comparison to the control, L-only- and L + 48/80-treated groups. A protective effect of L was shown against the deleterious effects of 48/80 which is associated with prevention of myocardial carnosine mobilization to histidine and histamine. These data support the role of carnosine as a nontoxic myocardial histidine reservoir which is mobilized in response to stress-induced increases in histamine requirements.

  1. High-amplitude theta wave bursts characterizing narcoleptic mice and patients are also produced by histamine deficiency in mice.

    PubMed

    Bastianini, Stefano; Lo Martire, Viviana; Berteotti, Chiara; Silvani, Alessandro; Ohtsu, Hiroshi; Lin, Jian-Sheng; Zoccoli, Giovanna

    2016-10-01

    Histamine and orexins are wake promoters released by hypothalamic neurons. The activity of histamine neurons is increased by orexin neurons. Recently, it has been shown that orexin deficiency entails high-amplitude theta wave bursts during rapid eye movement sleep and cataplexy in narcoleptic mice. The primary aim of this study was to assess whether histamine system is involved in high-amplitude theta wave burst generation during rapid eye movement sleep. The secondary aim was to assess the effects of combined histamine and orexin deficiency on high-amplitude theta wave bursts during rapid eye movement sleep in mice. Twelve histidine-decarboxylase knockout mice with congenital histamine deficiency, seven double mutant mice with combined deficiency of orexin neurons and histamine, and 11 wild-type control mice were studied with electrodes for sleep recordings and a telemetric blood pressure transducer. High-amplitude theta wave bursts during rapid eye movement sleep were detected in each of the histidine-decarboxylase knockout and double mutant mice, whereas only one burst was found in a wild-type control mouse. High-amplitude theta wave bursts occurred significantly more often and were significantly longer in double mutant than in histidine-decarboxylase knockout mice. In conclusion, it was demonstrated that, similarly to orexin, the chronic impairment of histamine entailed high-amplitude theta wave bursts during rapid eye movement sleep. The current data also suggested a synergistic role of orexin and histamine signalling on high-amplitude theta wave bursts during rapid eye movement sleep in mice. © 2016 European Sleep Research Society.

  2. ECL-cell histamine mobilization in conscious rats: effects of locally applied regulatory peptides, candidate neurotransmitters and inflammatory mediators.

    PubMed

    Norlén, P; Bernsand, M; Konagaya, T; Håkanson, R

    2001-12-01

    1. The ECL cells control gastric acid secretion by mobilizing histamine in response to circulating gastrin. In addition, the ECL cells are thought to operate under nervous control and to be influenced by local inflammatory processes. 2. The purpose of the present study was to monitor histamine mobilization from ECL cells in conscious rats in response to locally applied regulatory peptides, candidate neurotransmitters and inflammatory mediators. 3. Microdialysis probes were implanted in the submucosa of the acid-producing part of the rat stomach. Three days later, the agents to be tested were administered via the microdialysis probe and their effects on basal (48 h fast) and stimulated (intravenous infusion of gastrin-17, 3 nmol kg(-1) h(-1)) mobilization of ECL-cell histamine was monitored by continuous measurement of histamine in the perfusate (radioimmunoassay). 4. Locally administered gastrin-17 and sulfated cholecystokinin-8 mobilized histamine as did pituitary adenylate cyclase-activating peptide-27, vasoactive intestinal peptide, peptide YY, met-enkephalin, endothelin and noradrenaline, adrenaline and isoprenaline. 5. While gastrin, sulfated-cholecystokinin-8, met-enkephalin and isoprenaline induced a sustained elevation of the submucosal histamine concentration, endothelin, peptide YY, pituitary adenylate cyclase activating peptide, vasoactive intestinal peptide, noradrenaline and adrenaline induced a transient elevation. 6. Calcitonin gene-related peptide, galanin, somatostatin and the prostanoid misoprostol inhibited gastrin-stimulated histamine mobilization. 7. The gut hormones neurotensin and secretin and the neuropeptides gastrin-releasing peptide, neuropeptide Y and substance P failed to affect ECL-cell histamine mobilization, while motilin and neuromedin U-25 had weak stimulatory effects. Also acetylcholine, carbachol, serotonin and the amino acid neurotransmitters aspartate, gamma-aminobutyric acid, glutamate and glycine were inactive or weakly

  3. Influence of Formulation Factors and Compression Force on Release Profile of Sustained Release Metoprolol Tablets using Compritol® 888ATO as Lipid Excipient

    PubMed Central

    Patere, Shilpa N.; Kapadia, Chhanda J.; Nagarsenker, Mangal S.

    2015-01-01

    Tablets containing metoprolol succinate and Compritol® 888ATO in the ratio of 1:2 yielded the desired sustained release profile in phosphate buffer pH 6.8 when evaluated using USP type II paddle apparatus and was selected as the optimized formulation. Robustness of optimized formulation was assessed by studying the effect of factors like varying source of metoprolol succinate and Compritol® 888ATO, compression force and hydroalcoholic dissolution medium on the release profile. No significant difference (P>0.05) in release profile was observed when metoprolol succinate from three different sources and Compritol® 888ATO from two different batches were used. Release profile of sustained release tablets of metoprolol succinate in media containing various concentrations of ethanol was comparable with media devoid of ethanol as evaluated by f2 test. This indicated that release profile of sustained release tablets of metoprolol succinate was reliable with no significant change due to variation in source of active pharmaceutical ingredient, particularly due to particle size distribution. Sustained release tablets of metoprolol succinate yielded release pattern within specifications irrespective of presence or absence of ethanol in the medium indicating that release properties of Compritol® 888ATO matrix are not affected by ethanol. Tablets compressed at compression force of <100 kg/cm2 exhibited low hardness with total porosity of 15.39% and significantly increased (P<0.05) metoprolol succinate release as compared to tablets compressed at 2000 kg/cm2 with 6.90% of total porosity revealing influence of compression force. Compritol® 888ATO holds great potential in providing reliable and controlled release profile of highly water soluble metoprolol succinate. PMID:26798179

  4. Purification of an RNA polymerase II transcript release factor from Drosophila.

    PubMed

    Xie, Z; Price, D H

    1996-05-10

    Factor 2 was previously identified in Drosophila Kc cell nuclear extract (KcN) as an activity suppressing the appearance of long transcripts (Price, D. H., Sluder, A. E., and Greenleaf, A. L. (1987) J. Biol. Chem. 262, 3244-3255). A 154-kDa protein with factor 2 activity was purified to apparent homogeneity from KcN. An immobilized template assay indicated that factor 2 caused the release of transcripts by RNA polymerase II in an ATP-dependent manner. Some early elongation complexes were resistant to factor 2 action but became sensitive after treatment with 1 M KCl. In the absence of factor 2, transcription complexes still exhibited a low degree of processivity suggesting that factor 2 was only partially responsible for abortive elongation.

  5. Growth hormone secretion from chicken adenohypophyseal cells in primary culture: effects of human pancreatic growth hormone-releasing factor, thyrotropin-releasing hormone, and somatostatin on growth hormone release.

    PubMed

    Perez, F M; Malamed, S; Scanes, C G

    1987-03-01

    A primary culture of chicken adenohypophyseal cells has been developed to study the regulation of growth hormone (GH) secretion. Following collagenase dispersion, cells were exposed for 2 hr to vehicle (control) or test agents. Human pancreatic (tumor) growth hormone-releasing factor (hpGRF) and rat hypothalamic growth hormone-releasing factor stimulated GH release to similar levels. GH release was increased by the presence of dibutyryl cyclic AMP. Thyrotropin-releasing hormone (TRH) alone did not influence GH release; however, TRH plus hpGRF together exerted a synergistic (greater than additive) effect, increasing GH release by 100 to 300% over the sum of the values for each secretagogue acting alone. These relationships between TRH and hpGRF were further examined in cultured cells exposed to secretagogues for two consecutive 2-hr incubations. TRH pretreatment enhanced subsequent hpGRF-stimulated GH release by about 80% over that obtained if no secretagogue was present during the first incubation. In other experiments, somatostatin (SRIF) alone did not alter GH secretion. However, SRIF reduced hpGRF-stimulated GH release to levels found in controls. Furthermore, GH release stimulated by the presence of both TRH and hpGRF was lowered to control values by SRIF. The results of these studies demonstrate that a primary culture of chicken adenohypophyseal cells is a useful model for the study of GH secretion. Indeed, these results suggest that TRH and hpGRF regulate GH secretion by mechanisms which are not identical.

  6. Sprouty 2 binds ESCRT-II factor Eap20 and facilitates HIV-1 gag release.

    PubMed

    Medina, G N; Ehrlich, L S; Chen, M H; Khan, M B; Powell, M D; Carter, C A

    2011-07-01

    The four ESCRT (endocytic sorting complexes required for transport) complexes (ESCRT-0, -I, -II, and -III) normally operate sequentially in the trafficking of cellular cargo. HIV-1 Gag trafficking and release as virus-like particles (VLPs) require the participation of ESCRTs; however, its use of ESCRTs is selective and nonsequential. Specifically, Gag trafficking to release sites on the plasma membrane does not require ESCRT-0 or -II. It is known that a bypass of ESCRT-0 is achieved by the direct linkage of the ESCRT-I component, Tsg101, to the primary L domain motif (PTAP) in Gag and that bypass of ESCRT-II is achieved by the linkage of Gag to ESCRT-III through the adaptor protein Alix. However, the mechanism by which Gag suppresses the interaction of bound ESCRT-I with ESCRT-II is unknown. Here we show (i) that VLP release requires the steady-state level of Sprouty 2 (Spry2) in COS-1 cells, (ii) that Spry2 binds the ESCRT-II component Eap20, (iii) that binding Eap20 permits Spry2 to disrupt ESCRT-I interaction with ESCRT-II, and (iv) that coexpression of Gag with a Spry2 fragment that binds Eap20 increases VLP release. Spry2 also facilitated release of P7L-Gag (i.e., release in the absence of Tsg101 binding). In this case, rescue required the secondary L domain (YPX(n)L) in HIV-1 Gag that binds Alix and the region in Spry2 that binds Eap20. The results identify Spry2 as a novel cellular factor that facilitates release driven by the primary and secondary HIV-1 Gag L domains.

  7. Nerve growth factor released from a novel PLGA nerve conduit can improve axon growth

    NASA Astrophysics Data System (ADS)

    Lin, Keng-Min; Shea, Jill; Gale, Bruce K.; Sant, Himanshu; Larrabee, Patti; Agarwal, Jay

    2016-04-01

    Nerve injury can occur due to penetrating wounds, compression, traumatic stretch, and cold exposure. Despite prompt repair, outcomes are dismal. In an attempt to help resolve this challenge, in this work, a poly-lactic-co-glycolic acid (PLGA) nerve conduit with associated biodegradable drug reservoir was designed, fabricated, and tested. Unlike current nerve conduits, this device is capable of fitting various clinical scenarios by delivering different drugs without reengineering the whole system. To demonstrate the potential of this device for nerve repair, a series of experiments were performed using nerve growth factor (NGF). First, an NGF dosage curve was developed to determine the minimum NGF concentration for optimal axonal outgrowth on chick dorsal root ganglia (DRG) cells. Next, PLGA devices loaded with NGF were evaluated for sustained drug release and axon growth enhancement with the released drug. A 20 d in vitro release test was conducted and the nerve conduit showed the ability to meet and maintain the minimum NGF requirement determined previously. Bioactivity assays of the released NGF showed that drug released from the device between the 15th and 20th day could still promote axon growth (76.6-95.7 μm) in chick DRG cells, which is in the range of maximum growth. These novel drug delivery conduits show the ability to deliver NGF at a dosage that efficiently promotes ex vivo axon growth and have the potential for in vivo application to help bridge peripheral nerve gaps.

  8. The Effect of Vitamin D Treatment On Nerve Growth Factor (NGF) Release From Hippocampal Neurons

    PubMed Central

    GEZEN-AK, Duygu; DURSUN, Erdinç; YILMAZER, Selma

    2014-01-01

    Introduction Vitamin D, the main function of which is thought to be the maintenance of calcium and phosphate homeostasis and bone structure, has been shown in recent studies to have important roles in brain development as well. A certain vitamin D receptor (VDR) gene haplotype was reported, for the first time by our group, to increase the risk of developing Alzheimer’s disease. Our studies also showed that vitamin D prevents beta amyloid-induced calcium elevation and toxicity that target nerve growth factor (NGF) release in cortical neurons; beta amyloid suppresses VDR expression and the disruption of vitamin D-VDR pathway mimics beta amyloid-induced neurodegeneration. In this study, our aim was to investigate the effects of vitamin D on the NGF release from hippocampal neurons. Method Primary hippocampal neuron cultures that were prepared from 18-day-old Sprague-Dawley rat embryos were treated with vitamin D for 48 hours. The alteration in the NGF release was determined with ELISA. Cytotoxicity tests were also performed for all groups. Results The NGF release in vitamin D-treated group was significantly higher than in untreated control group. The protective effect of vitamin D against cytotoxicity was also observed. Conclusion Our results indicated that vitamin D regulates the release of NGF, a very important molecule for neuronal survival of hippocampal neurons as well as cortical neurons.

  9. Material-mediated proangiogenic factor release pattern modulates quality of regenerated blood vessels.

    PubMed

    Rich, Max H; Lee, Min Kyung; Baek, Kwanghyun; Jeong, Jae Hyun; Kim, Dong Hyun; Millet, Larry J; Bashir, Rashid; Kong, Hyunjoon

    2014-12-28

    Hydrogels designed to sustainably release bioactive molecules are extensively used to enhance tissue repair and regenerative therapies. Along this line, numerous efforts are made to control the molecular release rate and amount. In contrast, few efforts are made to control the molecular release pattern, and, subsequently, modulate the spatial organization of newly forming tissues, including blood vessels. Therefore, using a hydrogel printed to release vascular endothelial growth factor (VEGF) into a pre-defined pattern, this study demonstrates that spatial distribution of VEGF is important in guiding growth direction of new blood vessels, and also in retaining the structural integrity of pre-existing vasculature. Guided by a computational model, we fabricated a patch composed of micro-sized VEGF-releasing poly(ethylene glycol) diacrylate (PEGDA) hydrogel cylinders using an ink-jet printer. Interestingly, hydrogel printed with computationally optimized spacing created anisotropically aligned vasculature exclusively when the printed gel pattern was placed parallel to pre-existing blood vessels. In contrast, vascular sprouting from placing the printed gel pattern perpendicular to pre-existing vessels resulted in deformation and structural disintegration of the original vasculature. We envision that this study will be useful to better understand angiogenesis-modulated neovascularization and further improve the treatment quality for various wounds and tissue defects. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Elongation factor 1-alpha is released into the culture medium during growth of Giardia intestinalis trophozoites.

    PubMed

    Skarin, Hanna; Ringqvist, Emma; Hellman, Ulf; Svärd, Staffan G

    2011-04-01

    The molecular pathogenesis of the intestinal parasite Giardia intestinalis is still not fully understood but excretory-secretory products have been suggested to be important during host-parasite interactions. Here we used SDS-PAGE gels and MALDI-TOF analysis to identify proteins released by Giardia trophozoites during in vitro growth. Serum proteins (mainly bovine serum albumin) in the growth medium, bind to the parasite surface and they are continuously released, which interfere with parasite secretome characterization. However, we identified two released Giardia proteins: elongation factor-1 alpha (EF-1α) and a 58 kDa protein, identified as arginine deiminase (ADI). This is the first description of EF-1α as a released/secreted Giardia protein, whereas ADI has been identified in an earlier secretome study. Two genes encoding EF-1α were detected in the Giardia WB genome 35 kbp apart with almost identical coding sequences but with different promoter and 3' regions. Promoter luciferase-fusions showed that both genes are transcribed in trophozoites. The EF-1α protein localizes to the nuclear region in trophozoites but it relocalizes to the cytoplasm during host-cell interaction. Recombinant EF-1α is recognized by serum from giardiasis patients. Our results suggest that released EF-1α protein can be important during Giardia infections.

  11. Seed release by invasive thistles: the impact of plant and environmental factors

    PubMed Central

    Jongejans, Eelke; Pedatella, Nicholas M; Shea, Katriona; Skarpaas, Olav; Auhl, Richard

    2007-01-01

    Dispersal is a key process in biological studies of spatial dynamics, but the initiation of dispersal has often been neglected, despite strong indications that differential timing of dispersal can significantly affect dispersal distances. To investigate which plant and environmental factors determine the release of plumed seeds by the invasive thistles Carduus acanthoides and Carduus nutans, we exposed 192 flower heads of each species to increasing wind speeds in a full-factorial wind tunnel experiment with four air flow turbulence, three flower head wetness and two flower head temperature levels. The number of seed releases was highest under dry and turbulent conditions and from heads that had already lost a considerable number of seeds, but was not affected by flower head size, head angle or temperature. Inspection of the trials on video showed that higher wind speeds were needed to meet the seed release threshold in laminar flows and for C. acanthoides heads that had been wet for a longer time. Species differences were minimal, although seed release was more sensitive to lower levels of turbulence in the larger-headed and more open C. nutans heads. Knowledge of seed release biases towards weather conditions favourable for long-distance dispersal improves our understanding of the spread of invaders and allows managers to increase the efficiency of their containment strategies by applying them at crucial times. PMID:17666379

  12. Induction of release of tumor necrosis factor from human monocytes by staphylococci and staphylococcal peptidoglycans.

    PubMed Central

    Timmerman, C P; Mattsson, E; Martinez-Martinez, L; De Graaf, L; Van Strijp, J A; Verbrugh, H A; Verhoef, J; Fleer, A

    1993-01-01

    The role of cytokines in gram-positive infections is still relatively poorly defined. The purpose of this study was to establish whether or not intact staphylococci and purified peptidoglycans and peptidoglycan components derived from staphylococci are capable of stimulating the release of tumor necrosis factor (TNF) by human monocytes. We show here that intact staphylococci and purified peptidoglycans, isolated from three Staphylococcus epidermidis and three S. aureus strains, were indeed able to induce secretion of TNF by human monocytes in a concentration-dependent fashion. TNF release was detected by both enzyme immunoassay and the L929 fibroblast bioassay. In the enzyme immunoassay, a minimal concentration of peptidoglycan of 1 micrograms/ml was required to detect TNF release by monocytes, whereas in the bioassay a peptidoglycan concentration of 10 micrograms/ml was needed to detect a similar amount of TNF release. Peptidoglycan components such as the stem peptide, tetra- and pentaglycine, and muramyl dipeptide were unable to induce TNF release from human monocytes. PMID:8406805

  13. Novel systems for tailored neurotrophic factor release based on hydrogel and resorbable glass hollow fibers.

    PubMed

    Novajra, G; Tonda-Turo, C; Vitale-Brovarone, C; Ciardelli, G; Geuna, S; Raimondo, S

    2014-03-01

    A novel system for the release of neurotrophic factor into a nerve guidance channel (NGC) based on resorbable phosphate glass hollow fibers (50P2O5-30CaO-9Na2O-3SiO2-3MgO-2.5K2O-2.5TiO2 mol%) in combination with a genipin-crosslinked agar/gelatin hydrogel (A/G_GP) is proposed. No negative effect on the growth of neonatal olfactory bulb ensheathing cell line (NOBEC) as well as on the expression of pro- and anti-apoptotic proteins was measured in vitro in the presence of fiber dissolution products in the culture medium. For the release studies, fluorescein isothiocyanate-dextran (FD-20), taken as growth factor model molecule, was solubilized in different media and introduced into the fiber lumen exploiting the capillary action. The fibers were filled with i) FD-20/phosphate buffered saline (PBS) solution, ii) FD-20/hydrogel solution before gelation and iii) hydrogel before gelation, subsequently lyophilized and then filled with the FD-20/PBS solution. The different strategies used for the loading of the FD-20 into the fibers resulted in different release kinetics. A slower release was observed with the use of A/G_GP hydrogel. At last, poly(ε-caprolactone) (PCL) nerve guides containing the hollow fibers and the hydrogel have been fabricated.

  14. Synthesis of multilayered alginate microcapsules for the sustained release of fibroblast growth factor-1

    PubMed Central

    Khanna, Omaditya; Moya, Monica L; Opara, Emmanuel C; Brey, Eric M

    2010-01-01

    Alginate microcapsules coated with a permselective poly-L-ornithine (PLO) membrane have been investigated for the encapsulation and transplantation of islets as a treatment for type 1 diabetes. The therapeutic potential of this approach could be improved through local stimulation of microvascular networks in order to meet mass transport demands of the encapsulated cells. Fibroblast growth factor-1 (FGF-1) is a potent angiogenic factor with optimal effect occurring when it is delivered in a sustained manner. In this paper, a technique is described for the generation of multilayered alginate microcapsules with an outer alginate layer that can be used for the delivery of FGF-1. The influence of alginate concentration and composition (high mannuronic acid (M) or guluronic acid (G) content) on outer layer size and stability, protein encapsulation efficiency, and release kinetics was investigated. The technique results in a stable outer layer of alginate with a mean thickness between 113–164 µm, increasing with alginate concentration and G-content. The outer layer was able to encapsulate and release FGF-1 for up to thirty days, with 1.25% of high G alginate displaying the most sustained release. The released FGF-1 retained its biologic activity in the presence of heparin, and the addition of the outer layer did not alter the permselectivity of the PLO coat. This technique could be used to generate encapsulation systems that deliver proteins to stimulate local neovascularization around encapsulated islets. PMID:20725969

  15. Release of mitochondrial apoptogenic factors and cell death are mediated by CK2 and NADPH oxidase.

    PubMed

    Kim, Gab Seok; Jung, Joo Eun; Narasimhan, Purnima; Sakata, Hiroyuki; Yoshioka, Hideyuki; Song, Yun Seon; Okami, Nobuya; Chan, Pak H

    2012-04-01

    Activation of the NADPH oxidase subunit, NOX2, and increased oxidative stress are associated with neuronal death after cerebral ischemia and reperfusion. Inhibition of NOX2 by casein kinase 2 (CK2) leads to neuronal survival, but the mechanism is unknown. In this study, we show that in copper/zinc-superoxide dismutase transgenic (SOD1 Tg) mice, degradation of CK2α and CK2α' and dephosphorylation of CK2β against oxidative stress were markedly reduced compared with wild-type (WT) mice that underwent middle cerebral artery occlusion. Inhibition of CK2 pharmacologically or by ischemic reperfusion facilitated accumulation of poly(ADP-ribose) polymers, the translocation of apoptosis-inducing factor (AIF), and cytochrome c release from mitochondria after ischemic injury. The eventual enhancement of CK2 inhibition under ischemic injury strongly increased 8-hydroxy-2'-deoxyguanosine and phosphorylation of H2A.X. Furthermore, CK2 inhibition by tetrabromocinnamic acid (TBCA) in SOD1 Tg and gp91 knockout (KO) mice after ischemia reperfusion induced less release of AIF and cytochrome c than in TBCA-treated WT mice. Inhibition of CK2 in gp91 KO mice subjected to ischemia reperfusion did not increase brain infarction compared with TBCA-treated WT mice. These results strongly suggest that NOX2 activation releases reactive oxygen species after CK2 inhibition, triggering release of apoptogenic factors from mitochondria and inducing DNA damage after ischemic brain injury.

  16. Macrophage activation by factors released from acetaminophen-injured hepatocytes: Potential role of HMGB1

    SciTech Connect

    Dragomir, Ana-Cristina; Laskin, Jeffrey D.; Laskin, Debra L.

    2011-06-15

    Toxic doses of acetaminophen (AA) cause hepatocellular necrosis. Evidence suggests that activated macrophages contribute to the pathogenic process; however, the factors that activate these cells are unknown. In these studies, we assessed the role of mediators released from AA-injured hepatocytes in macrophage activation. Treatment of macrophages with conditioned medium (CM) collected 24 hr after treatment of mouse hepatocytes with 5 mM AA (CM-AA) resulted in increased production of reactive oxygen species (ROS). Macrophage expression of heme oxygenase-1 (HO-1) and catalase mRNA was also upregulated by CM-AA, as well as cyclooxygenase (COX)-2 and 12/15-lipoxygenase (LOX). CM-AA also upregulated expression of the proinflammatory chemokines, MIP-1{alpha} and MIP-2. The effects of CM-AA on expression of COX-2, MIP-1{alpha} and MIP-2 were inhibited by blockade of p44/42 MAP kinase, suggesting a biochemical mechanism mediating macrophage activation. Hepatocytes injured by AA were found to release HMGB1, a potent macrophage activator. This was inhibited by pretreatment of hepatocytes with ethyl pyruvate (EP), which blocks HMGB1 release. EP also blocked CM-AA induced ROS production and antioxidant expression, and reduced expression of COX-2, but not MIP-1{alpha} or MIP-2. These findings suggest that HMGB1 released by AA-injured hepatocytes contributes to macrophage activation. This is supported by our observation that expression of the HMGB1 receptor RAGE is upregulated in macrophages in response to CM-AA. These data indicate that AA-injured hepatocytes contribute to the inflammatory environment in the liver through the release of mediators such as HMGB1. Blocking HMGB1/RAGE may be a useful approach to limiting classical macrophage activation and AA-induced hepatotoxicity. - Research Highlights: > These studies analyze macrophage activation by mediators released from acetaminophen-damaged hepatocytes. > Factors released from acetaminophen-injured hepatocytes induce

  17. New insights into the role of histamine in subventricular zone-olfactory bulb neurogenesis

    PubMed Central

    Eiriz, Maria F.; Valero, Jorge; Malva, João O.; Bernardino, Liliana

    2014-01-01

    The subventricular zone (SVZ) contains neural stem cells (NSCs) that generate new neurons throughout life. Many brain diseases stimulate NSCs proliferation, neuronal differentiation and homing of these newborns cells into damaged regions. However, complete cell replacement has never been fully achieved. Hence, the identification of proneurogenic factors crucial for stem cell-based therapies will have an impact in brain repair. Histamine, a neurotransmitter and immune mediator, has been recently described to modulate proliferation and commitment of NSCs. Histamine levels are increased in the brain parenchyma and at the cerebrospinal fluid (CSF) upon inflammation and brain injury, thus being able to modulate neurogenesis. Herein, we add new data showing that in vivo administration of histamine in the lateral ventricles has a potent proneurogenic effect, increasing the production of new neuroblasts in the SVZ that ultimately reach the olfactory bulb (OB). This report emphasizes the multidimensional effects of histamine in the modulation of NSCs dynamics and sheds light into the promising therapeutic role of histamine for brain regenerative medicine. PMID:24982610

  18. Studies on the biological effects of ozone: 10. Release of factors from ozonated human platelets.

    PubMed Central

    Valacchi, G; Bocci, V

    1999-01-01

    In a previous work we have shown that heparin, in the presence of ozone (O3), promotes a dose-dependent platelet aggregation, while after Ca2+ chelation with citrate, platelet aggregation is almost negligible. These results led us to think that aggregation may enhance the release of platelet components. We have here shown that indeed significantly higher amount of platelet-derived growth factor (PDGF), transforming growth factor beta1 (TGF-beta1) and interleukin-8 (IL-8) are released in a dose-dependent manner after ozonation of heparinised platelet-rich plasma samples. These findings may explain the enhanced healing of torpid ulcers in patients with chronic limb ischemia treated with O3 autohaemoteraphy (O3-AHT). PMID:10704074

  19. Studies on the biological effects of ozone: 10. Release of factors from ozonated human platelets.

    PubMed

    Valacchi, G; Bocci, V

    1999-01-01

    In a previous work we have shown that heparin, in the presence of ozone (O3), promotes a dose-dependent platelet aggregation, while after Ca2+ chelation with citrate, platelet aggregation is almost negligible. These results led us to think that aggregation may enhance the release of platelet components. We have here shown that indeed significantly higher amount of platelet-derived growth factor (PDGF), transforming growth factor beta1 (TGF-beta1) and interleukin-8 (IL-8) are released in a dose-dependent manner after ozonation of heparinised platelet-rich plasma samples. These findings may explain the enhanced healing of torpid ulcers in patients with chronic limb ischemia treated with O3 autohaemoteraphy (O3-AHT).

  20. Growth factor and co-receptor release by structural regulation of substrate metalloprotease accessibility

    PubMed Central

    Parra, Liseth M.; Hartmann, Monika; Schubach, Salome; Ma, Junzhi; Herrlich, Peter; Herrlich, Andreas

    2016-01-01

    Release of cytokines, growth factors and other life-essential molecules from precursors by a-disintegrin-and-metalloproteases (ADAMs) is regulated with high substrate-specificity. We hypothesized that this is achieved by cleavage-regulatory intracellular-domain (ICD)-modifications of the precursors. We show here that cleavage-stimuli-induced specific ICD-modifications cause structural substrate changes that enhance ectodomain sensitivity of neuregulin-1 (NRG1; epidermal-growth-factor) or CD44 (receptor-tyrosine-kinase (RTK) co-receptor) to chymotrypsin/trypsin or soluble ADAM. This inside-out signal transfer required substrate homodimerization and was prevented by cleavage-inhibitory ICD-mutations. In chimeras, regulation could be conferred to a foreign ectodomain, suggesting a common higher-order structure. We predict that substrate-specific protease-accessibility-regulation controls release of numerous ADAM substrates. PMID:27876763

  1. Insulin antagonizes the phagocytosis stimulating action of histamine in Tetrahymena.

    PubMed

    Csaba, G; Darvas, Z

    1992-02-01

    Histamine increased specifically the phagocytic activity of the unicellular Tetrahymena, whereas insulin had no influence on it. Insulin antagonized the phagocytosis stimulating action of histamine after simultaneous exposure and after preexposure two days earlier as well, although in the latter case to a lesser degree. Double exposure to a combination of histamine+insulin didn't influence the phagocytic activity at all, demonstrating the histamine antagonizing effect of insulin in this model.

  2. Functional Significance of the Signal Peptides of Corticotropin-Releasing Factor Receptors.

    PubMed

    Schülein, Ralf; Gibert, Arthur; Rutz, Claudia

    2017-02-23

    The corticotropin releasing factor (CRF) receptors belong to the large family of G protein-coupled receptors (GPCRs) and must be transported to the plasma membrane to function properly. The first step of the intracellular transport of GPCRs is their insertion into the membrane of the endoplasmic reticulum (ER). This process is mediated by the translocon complex of the ER membrane and the signal sequences of the receptors. Most GPCRs possess signal sequences which form part of the mature proteins, the so called signal anchor sequences (usually transmembrane domain 1). The CRF recept