Mechanism Of Histamine Release Research Articles

Histamine in the neocortex: Towards integrating multiscale effectors.

Histamine is a modulatory neurotransmitter, which has received relatively less attention in the central nervous system than other neurotransmitters. The functional role of histamine in the neocortex, the brain region that controls higher-order cognitive functions such as attention, learning and memory, remains largely unknown. This article focuses on the emerging roles and mechanisms of histamine release in the neocortex. We describe gaps in current knowledge and propose the application of interdisciplinary tools to dissect the detailed multiscale functional logic of histaminergic action in the neocortex ranging from sub-cellular, cellular, dendritic and synaptic levels to microcircuits and mesoscale effects.

The discovery of IgE 50 years later

In 1906, Von Pirquet1 used the term supersensitivity without immunity to describe (1) symptoms of inhalant allergy, (2) positive immediate skin test results, and (3) the fact that the results of other tests of immunity were not positive in these patients. The other tests he referred to were precipitin tests and complement fixation. Thus, he opened up the question of serum tests for supersensitivity. In 1919, Ramirez2 reported that a patient who had received a blood transfusion from a horse allergic donor became allergic to horse dander. At this point, Prausnitz and Kustner3 set out to investigate whether the serum of allergic individuals contained a factor or factors that could sensitize the skin. In 1921, they reported that the local injection of serum from a fish allergic individual, Kustner, to an individual who was only allergic to pollen, Prausnitz, would transfer specific sensitivity.3 This transfer of sensitivity came to be known as the P-K test and was used widely to study sensitivity not only to common allergens but also to extracts as diverse as those obtained from schistosomes.4,5 Furthermore, in New York, Cooke et al6 identified that there were other antibodies in the serum that increased during desensitization treatment and could block the skin-sensitizing activity. By the 1950s, it was clear that the transferred sensitivity was specific, that it could be diluted extensively, and that the skin remained locally sensitive for days if not weeks after the injection of serum.7,8 It was also already clear that the ability to sensitize the skin was lost after moderate heating of the serum.7 Several studies had also been reported on the physical properties of P-K activity. Indeed, Heimlich et al9 at Cal Tech reported on the sedimentation properties of skin-sensitizing antibodies in 1960. However, the studies before 1964 had not succeeded in defining the nature of these antibodies.

Basophils are elevated in nasal polyps of patients with chronic rhinosinusitis without aspirin sensitivity

Basophils are elevated in nasal polyps of patients with chronic rhinosinusitis without aspirin sensitivity

Mitochondrial signaling for histamine releases in laser‐irradiated RBL‐2H3 mast cells

The low power laser irradiation (LPLI) can promote the wound healing, but the mechanism is still not fully understood. We have found in our previous work that the LPLI induces mast cells to release the histamine and thus suggested that the increased histamine release is probably one of the causes for promoting the wound healing since mast cells have been found to play positive roles in the process of wound healing. This study aims to explore the mechanism of histamine release in RBL-2H3 mast cells under laser irradiations. The wavelength effect of laser irradiations, the permeability function of mitochondrial membrane, the Bcl-2 effect, the cytosolic alkalinization and the increment of intracellular Ca(2+) ([Ca(2+)](i)), on histamine release in RBL-2H3 cells were studied, respectively, with the corresponding fluorescence probes. The action bands of laser irradiations were consistent with the absorption bands of cytochrome c oxidase, suggesting that cytochrome c oxidase is the photoacceptor. After laser irradiation, (1) the cytochrome c releases from mitochondrial to cytosol reflecting an increased permeability of mitochondrial membrane, (2) the cytosolic alkalinization appears, (3) [Ca(2+)](i) increases, and (4) finally the enhancement of histamine release occurs. When Bcl-2 was used to inhibit the permeability of mitochondrial membrane these cellular signaling from (1) to (4) were all suppressed obviously. As a photoacceptor, cytochrome c oxidase absorbs incident photons and initiates the mitochondrial signaling. When the signals are transferred from the mitochondrial to the cytosol, the cytosolic alkalinization appears leading to the opening of a Ca(2+) channel on the membrane, the transient receptor potential vanilloid (TRPV), and an increment of [Ca(2+)](i). The increased [Ca(2+)](i) consequently mediates an enhanced histamine release. Such a responding chain is a suggested mechanism to understand the histamine release in RBL-2H3 cells under laser irradiations.

The Inhibitory Mechanism of Rebamipide on the Mediator Release in the Guinea Pig Lung Mast Cells Activated with Specific Antigen-Antibody Reactions

This study aim was to assess the effects of rebamipide on the mechanism of histamine release and biosynthesis and release of leukotrienes caused by mast cell activation. We purified mast cells from guinea pig lung tissues by the use of enzyme digestion, the rough and the discontinuous density percoll gradient method. Mast cells were sensitized with IgG1 (anti-OVA) antibody and challenged with ovalbumin. Mast cells were also stimulated with A23187 and the intracellular Ca²⁺ level was measured. Histamine and leukotrienes were measured by automated fluorometric analyzer and radioimmunoassay, respectively. The intracellular Ca²⁺ level was analyzed using a confocal laser scanning microscope. Protein kinase C (PKC) activity was determined by protein phosphorylated with [γ-³²P]ATP. The phospholipase D activity was assessed by the labeled phosphatidylalcohol. Mass 1,2-diacylglycerol (DAG) was measured by the [³H]DAG produced when prelabeled with [³H]myristic acid. PLA₂ activity was determined by measuring the arachidonic acid released from the labeled phospholipids. Rebamipide decreased the releases of histamine and leukotrienes, and completely blocked Ca²⁺ influx during mast cell activation by antigen-antibody reactions. It also decreased the release of histamine and leukotrienes during mast cell activation by A23187. The PKC and PLD activities were also decreased by rebamipide in a dose-dependent manner. Rebamipide inhibited the mass DAG production and PLA₂ activity during mast cell activation. The data suggest that rebamipide inhibits intracellular signals and blocks Ca²⁺ influx in mast cells activated by specific antigen-antibody reactions, which in turn inhibits histamine release and leukotriene generation.

NSAID intolerance in chronic idiopathic urticaria: A study of its relationship with histamine-releasing activity of patients’ sera

about one fourth of patients with chronic idiopathic urticaria (CIU) experience flares of hives after taking chemically unrelated nonsteroidal anti-inflammatory drugs (NSAID). The reasons for such intolerance are still elusive. this study aimed to investigate NSAID intolerance in patients with CIU in view of the in vivo and in vitro histamine releasing activity of their sera. 117 adults (M/F 41/76) with CIU underwent intradermal test with autologous serum, and the ability of their sera to induce histamine release from normal blood donors was evaluated. NSAID intolerance was ascertained by careful interview. overall, 32/117 (27 %) patients reported NSAID intolerance. The prevalence on NSAID intolerance did not differ in the three subgroups: negative on both in vivo and in vitro tests (9/36; 25 %), positive or intradermal test but negative on basophil histamine release assay (16/58; 28 %), or positive on both in vivo and in vitro tests (7/23; 30 %). in patients with CIU intolerance to NSAID does not depend on the mechanism of histamine release.

Mechanism of histamine release induced by levofloxacin, a fluoroquinolone antibacterial agent

The present study was designed to clarify the mechanism of histamine release caused by levofloxacin, a fluoroquinolone antibacterial agent, using rat peritoneal mast cells. Levofloxacin induced a concentration-dependent histamine secretion from 300 μg/ml without lactate dehydrogenase leakage, and the release was rapidly completed within 30 s. This action was dependent on temperature, energy, pH and intracellular Ca 2+, similarly to the effect of compound 48/80, a basic compound. Unlike that with the calcium ionophore A23187, histamine secretion due to levofloxacin or compound 48/80 was prevented by pretreatment with either pertussis toxin or benzalkonium chloride, a selective inhibitor of G proteins of G i subtypes. Moreover, the histamine release elicited by levofloxacin or compound 48/80 was suppressed by hydrolysis of sialic acid residues on the cell surface brought about by neuraminidase. These results demonstrate that the mechanism by which levofloxacin exerts histamine release may be closely linked to activation of pertussis toxin-sensitive G proteins.

Urticaria.

Urticaria.

Several mechanisms for histamine release during laparoscopic cholecystectomy in human subjects: Impact of plasma catecholamines for differentiation.

Several mechanisms for histamine release during laparoscopic cholecystectomy in human subjects: Impact of plasma catecholamines for differentiation.

Histamine: the quintessential mediator.

Histamine is unique in being the only substance described to date which fulfils all of the criteria established by Dale for an inflammatory mediator. Thus, histamine is known to cause the "Triple Response" of Lewis and to act via H1 and H2 receptors to produce vasodilation and increased vascular permeability; elevated levels of histamine are found in inflamed tissue; histamine is produced and stored in mast cells and there are established mechanisms for histamine release via mast cell surface receptors; and antihistamines alleviate the clinical manifestations of histamine release. There have been several recent advances in our understanding of histamine pharmacology and of the pathomechanisms of chronic idiopathic urticaria (CIU), a disease in which histamine plays an important role. Two new histamine receptors have been identified, the inhibitory (H3) receptor and the intracellular (H(ic)) receptor involved in cell proliferation. There is now evidence that mast cell derived histamine release in patients with CIU is due to an autoimmune disease, mediated by autoantibodies to the alpha-subunit of the high affinity IgE receptor on mast cells and basophils. Removal of these autoantibodies by plasmapheresis, or treatment with intravenous immunoglobulins may cause clinical remission. Cyclosporin A has also been found to be of benefit to some patients with CIU probably due to a mast cell "stabilising" effect, leading to reduced release of histamine and other mediators. This article reviews our current knowledge on histamine, its role, receptors and mechanisms for release.

Dual inhibitory pathways link antral somatostatin and histamine secretion in human, dog, and rat stomach

Background & Aims The secretion and function of antral histamine are not known. The aims of this study were to characterize the mechanisms of histamine release from the gastric antrum of humans, dogs, and rats and to determine whether histamine can influence the secretion of somatostatin and gastrin. Methods Somatostatin, gastrin, and histamine secretion from superfused antral segments was measured using radioimmunoassay. Results Superfusion with thioperamide (H 3 antagonist) increased somatostatin and decreased gastrin and histamine secretion in all three species; superfusion with (r)-α-methylhistamine (H 3 agonist) had the opposite effect. The pattern implied that endogenous histamine, acting via H 3 receptors, exerts an inhibitory paracrine influence on somatostatin secretion, which in turn regulates gastrin secretion. Superfusion with somatostatin antibody increased histamine secretion; the increase was not affected by the gastrin antagonist L-365,260, implying that it was not mediated by the concurrent increase in gastrin but by suppression of an inhibitory pathway linking somatostatin and histamine. Superfusion with methacholine alone and in the presence of either the H 3 agonist or antagonist confirmed the existence of reciprocal inhibitory pathways linking somatostatin and histamine. Conclusions Antral histamine in humans, dogs, and rats is linked to antral somatostatin via reciprocal inhibitory paracrine pathways that serve to amplify the regulatory influence of somatostatin.

Ca2+-activated outward-rectifier K+ channels and histamine release by rat gastric enterochromaffin-like cells

Gastric enterochromaffin-like (ECL) cells were isolated from rat gastric fundic mucosa by Percoll density-gradient centrifugation and counter-flow elutriation. About 67% of cells in the purified cell suspension were ECL cells, which were reacted with anti-histidine decarboxylase antibody. A23187, a calcium ionophore, at 0.1-10 μM induced histamine release from the ECL cell-rich suspension, indicating that the Ca 2+ pathway is involved in the mechanism of histamine release from ECL cells. A23187 at 5 μM significantly increased outward-rectifier cationic current in 62% of cells in the ECL cell-rich fraction. A23187-sensitive cells showed acridine orange uptake. In single-channel recordings, a Ca 2+ -dependent outward-rectifier K + channel of large conductance (146 ± 22 picosiemens) was found in the cell that showed acridine orange uptake. The channel opened in a voltage-dependent manner at 0.1 μM of intracellular free Ca 2+ concentration. These results may suggest that opening of the Ca 2+ -activated K + channel is one of the steps involved in the mechanism of histamine release in ECL cells.

Ca 2+-activated outward-rectifier K + channels and histamine release by rat gastric enterochromaffin-like cells

Gastric enterochromaffin-like (ECL) cells were isolated from rat gastric fundic mucosa by Percoll density-gradient centrifugation and counter-flow elutriation. About 67% of cells in the purified cell suspension were ECL cells, which were reacted with anti-histidine decarboxylase antibody. A23187, a calcium ionophore, at 0.1-10 μM induced histamine release from the ECL cell-rich suspension, indicating that the Ca 2+ pathway is involved in the mechanism of histamine release from ECL cells. A23187 at 5 μM significantly increased outward-rectifier cationic current in 62% of cells in the ECL cell-rich fraction. A23187-sensitive cells showed acridine orange uptake. In single-channel recordings, a Ca 2+-dependent outward-rectifier K + channel of large conductance (146 ± 22 picosiemens) was found in the cell that showed acridine orange uptake. The channel opened in a voltage-dependent manner at 0.1 μM of intracellular free Ca 2+ concentration. These results may suggest that opening of the Ca 2+-activated K + channel is one of the steps involved in the mechanism of histamine release in ECL cells.

Mechanism of histamine release by endothelin-1 distinct from that by antigen in mouse bone marrow-derived mast cells

The mechanisms of endothelin-1-induced histamine release were examined and compared with those responsible for antigen-induced release by using passively sensitized mouse bone marrow-derived mast cells and various drugs that may influence histamine release. The following results were obtained: (1) Although islet-activating protein potently inhibited endothelin-1-induced histamine release, it did not affect the antigen-induced release. (2) Histamine release induced by endothelin-1 was relatively more sensitive to ethylenediaminetetraacetic acid than that induced by antigen, although, extracellular Ca 2+ is a requisite for both types of the release. (3) ( 8R ∗, 9S ∗, 11S ∗ )-(−)-9-hydroxy-9-methoxycarbonyl-8-methyl- 2,3,9,10-tetrahydro-8, 11-epoxy-1 H,8 H,11 H-2,7b,11a-triazadibenzo[ a,g]cycloocta[ c,d,e]trinden-1-one and ( 8R ∗, 9S ∗, 11S ∗ )-(−)-9-hydroxy-9-methoxycarbonyl-8-methyl-14- n-propoxy- 2,3,9,10-tetrahydro-8,11-epoxy-1 H,8 H,11 H-2,7b,11a-triazadibenzol[ a,g]cycloota-[ c,d,e]trinden-1-one, which possibly inhibit protein kinases, strongly inhibited antigen-induced histamine release, while these drugs alone did not inhibit endothelin-1-induced release. (4) Staurosporine, a non-selective protein kinase inhibitor, prevented the elevation of cytosolic Ca 2+ concentrations induced by antigen, whereas that induced by endothelin-1 was not influenced; histamine release induced by either stimulus was greatly inhibited by the drug. These results indicate and/or suggest that some biological events induced by endothelin-1 leading to histamine release are different from those involved in the histamine release induced by antigen.

The mechanism of histamine release induced by pilocarpine from different tissues: studies on rat peritoneal mast cells.

Pilocarpine releases histamine from mast cells of cat submandibular gland and rat liver. In the salivary gland, histamine is released into the saliva and venous outflow. Atropine blocks the salivation, but not histamine release from the submandibular gland into the blood. Histamine release from the gland could be due to a direct action of pilocarpine on tissue mast cells or to an indirect action of mediators (acetylcholine and peptides). These hypotheses were further investigated in our present studies on rat peritoneal mast cells. Our results show: (1) histamine release from rat peritoneal mast cells induced by pilocarpine (ED50 = 1.7 x 10(-2) mol/l) occurs at 1000-fold higher concentrations than by substance P (ED50 = 1.7 x 10(-5) mol/l) and in 6.5-fold higher concentrations than by atropine (ED50 = 2.6 x 10(-3) mol/l), (2) pilocarpine injected directly into the rat peritoneal cavity causes histamine release from peritoneal mast cells in 1.8-fold higher concentrations than from isolated rat peritoneal mast cells. These results would support the hypothesis that histamine release from cat submandibular gland is caused by peptidergic co-transmission during the stimulation of the organ.

Lack of role for mononuclear cell-derived histamine releasing factors in occupational asthma due to western red cedar.

Occupational asthma due to Western Red Cedar (WRCA) is attributed to sensitization to plicatic acid (PA), but does not appear to be dependent on PA-specific IgE antibodies. Exposure to PA induces histamine release in vivo and in vitro, so if IgE is not important, other mechanisms of histamine release must presumably operate in WRCA. To explore the possible role of histamine-releasing factors in WRCA, peripheral blood mononuclear cells were obtained and cultured with PA, PA-albumin conjugate plicatic acid-human serum albumin (PA-HSA), grass pollen or Concanavalin A using a standard histamine releasing factor (HRF) generation protocol. Supernatants were dialysed to remove endogenous histamine and then assayed for histamine releasing activity using human basophils as targets and a Con A-induced bulk supernatant as an internal HRF standard. In contrast to some previous reports, spontaneous HRF release from the peripheral blood mononuclear cells (PBMC) of WRCA patients (n=9) and atopic asthmatic subjects (n=5) was not elevated compared with the non-asthmatic controls (n=11; five atopic and six non-atopic). Both PA and PA-HSA induced the production of small amounts of HRF by PBMC of WRCA patients, but a similar degree of HRF generation was also observed in PBMC from the atopic asthmatic, atopic nonasthmatic, and non-atopic subjects. In contrast, grass pollen induced the production of HRF by PBMC from the subjects with positive skin tests to grass pollen but not by PBMC of non-atopic subjects, confirming that our methods and assay were capable of detecting antigen-specific HRF production. Since neither PA nor PA-HSA induced significantly elevated HRF production from PBMC of WRCA patients, it seems unlikely that PA-induced HRFs play a substantial role in the pathogenesis of WRCA.

Histamine secretion from rat enterochromaffinlike cells

Background: In vivo studies have suggested an important role for gastric enterochromaffinlike (ECL) cells in mediating acid secretion. Direct evidence for this function is lacking and requires a preparation of highly purified ECL cells. This work investigates the possible role and mechanism of histamine release from the ECL cell in the peripheral regulation of acid secretion, using purified ECL cells from rat fundic mucosa. Methods: A combination of elutriation and density-gradient centrifugation was used to purify rat fundic ECL cells. Enrichment was determined by the presence of acidic vacuoles containing a V type adenosine triphosphatase, electron microscopy, immunostaining, and histamine content and release. Results: ECL cells were enriched at least 65-fold with respect to the fundic epithelium. Gastrin (EC50 0.2 nmol/L) and cholecystokinin octapeptide (nonsulfated, EC50 0.04 nmol/L) stimulated histamine release in a time- and dose-dependent manner, suggesting a CCK-B receptor subtype, confirmed by the inhibition of gastrin/CCK stimulation with the CCK-B antagonist L365,260. Somatostatin also inhibited gastrin-mediated histamine release. Single cell imaging showed that gastrin elevated intracellular cytosolic calcium concentration biphasically. Carbachol and the C kinase activator 120-tetradecanoylphorbol-13-acetate also stimulated histamine release. Epinephrine (blocked by propranolol), forskolin, and dibutyryl-5′-cyclic adenosine monophosphate were also effective, implicating a β-adrenergic pathway. The H3 agonist R-α-methyl-histamine inhibited, whereas the H3-antagonist thioperamide potentiated gastrin/CCK stimulated histamine release. Conclusions: These in vitro results support a central role for the ECL cell in the peripheral regulation of gastric acid secretion.

IN VITRO DISPLACEMENT OF VASOACTIVE MEDIATORS FROM PLASMA PROTEINS: A POSSIBLE MECHANISM FOR PSEUDO-ALLERGIC REACTIONS TO NEUROMUSCULAR BLOCKING DRUGS

We have studied the release of prostaglandin F2 alpha (PGF2 alpha) and histamine from serum proteins by neuromuscular blocking drugs using equilibrium dialysis, with tracer quantities of radio-labelled mediators as probes. Small concentrations (0.05-0.25 mmol litre-1) of competitive neuromuscular blocking drugs displaced 16-67% of bound histamine. Greater concentrations of suxamethonium (2 mmol litre-1) were required for histamine displacement (19%). There was a significant release of PGF2 alpha by atracurium 1 mmol litre-1 and pancuronium 0.69 mmol litre-1. These findings suggest an alternative mechanism of histamine release by neuromuscular blocking drugs which may be relevant to adverse reactions during use.

Effects of amiloride and furosemide on histamine release from human leukocytes induced by anti-IgE antibody

Inhalation of the “loop” diuretic furosemide inhibits both earlyand late-phase bronchospasm in response to allergen bronchoprovocation in patients with allergic asthma. I-3 Inhibition of histamine release from airway mast cells has been proposed as a possible mechanism. Amiloride, an inhibitor of the sodium/proton (Na’ /H ‘) antiport system, has previously been shown to inhibit the contraction of isolated, passively sensitized guinea pig trachea smooth muscle in response to antigen challenge, and even appears to interfere with sensitization itself.4 This effect is believed to be a result of alteration of sodium influx at the level of the cell membrane. In addition to its effects on smooth muscle, amiloride and its analogs have been shown to inhibit tritiated serotonin release from dinitrophenol sensitized rat basophilic leukemia cells (RBL-2H3) in response to antigen challenge. This effect is apparently mediated through specific inhibition of a sodiumdependent calcium influx pathway.” In this study we investigated the effects of varying concentrations of amiloride and furosemide on histamine release from human leukocytes induced by anti-IgE antibody to determine if a concentration-dependent inhibition occurs that may explain, in part, the observed effects on asthma and offer insight into the mechanism of histamine release. The histamine release assay was performed with use of a histamine radioimmunoassay kit purchased from AMAC, Inc., Westbrook, Maine. The four subjects for this study had a history of either asthma or allergic rhinitis (or both) and multiple positive skin

Vancomycin-induced release of histamine from rat peritoneal mast cells and a rat basophil cell line (RBL-1)

Rapid intravenous administration of the glycopeptide antibiotic, vancomycin, may cause a hypotensive reaction which can usually be prevented by infusing vancomycin in dilute solutions. The release of histamine from circulating cells such as basophils and tissue mast cells has been implicated in hypotensive reactions since the effects can be prevented by antihistamine pretreatment. The direct effects of vancomycin on histamine release were therefore investigated in rat peritoneal mast cells and rat leukemic basophils (RBL-1 cells). Suspension cultures of mast cells or RBL-1 cells were exposed to vancomycin for 30-60 minutes at concentrations comparable to those infused clinically (2.28 or 4.56 mg/ml). Vancomycin induced a time- and dose-dependent release of histamine into the culture media from both cell types. The reference degranulating agent, Compound 48/80 (CP 48/80), was also shown to induce histamine release from mast cells and RBL-1 cells. Mast cells were significantly more sensitive to vancomycin and CP 48/80 than RBL-1 cells and, unlike RBL-1 cells, were responsive to the inhibitory effects of cromolyn sodium on histamine release. Cromolyn sodium did not inhibit vancomycin-induced histamine release in RBL-1 or mast cells. Morphologically, mast cells exposed to either vancomycin or CP 48/80 exhibited dose-related degranulation. On the other hand, treatment-related degranulation effects of either vancomycin or CP 48/80 on RBL-1 cells could not be reliably distinguished from controls by qualitative evaluation. Based upon these findings it is concluded that mast cells may represent a more useful model to evaluate the potential of investigational agents to release histamine and to study mechanisms of histamine release than RBL-1 cells.