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PubMed1991

Refractoriness for ultrasonically nebulized distilled water and histamine after histamine challenge.

Refractoriness for bronchial provocation frequently occurs after different challenge tests used to assess bronchial hyperresponsiveness in asthmatic patients. We investigated whether histamine inhalation could cause refractoriness for bronchoconstriction induced by ultrasonically nebulized distilled water (UNDW) and whether histamine causes tachyphylaxis for a subsequent histamine challenge in nine stable asthmatic patients. Preinhalation of histamine induced a significant diminished bronchoconstrictor response to UNDW cumulative dose of inhaled UNDW causing a 20% fall in forced expired volume in 1 s. The mean increased from 3.5 +/- 0.8 to 11.8 +/- 2.6 (SE) ml after histamine challenge (P less than 0.01). However, repeated inhalation of histamine did not change the bronchoconstrictor response to histamine within 1 h after rechallenge (P greater than 0.5). The magnitude of refractoriness for UNDW inhalation after preinhalation of histamine was correlated to the bronchoconstrictor response to histamine (r = 0.73, P less than 0.05). We conclude that inhaled histamine can induce refractoriness for UNDW, which seems to be related to the degree of bronchial hyperresponsiveness.

Adult↗
PubMed2006

Recent advances in molecular pharmacology of the histamine systems: immune regulatory roles of histamine produced by leukocytes.

Accumulating evidence has highlighted the importance of histamine in immune responses. The H1 receptor is involved not only in allergic inflammatory reactions but also in augmentation of helper T cell (Th)1 responses, whereas H2 receptor suppresses Th responses and participates in immune tolerance through interleukin-10 and transforming growth factor-beta. Identification of the H4 receptor, which binds to histamine with high affinity and of which expression is limited to the hematopoietic system, has enhanced the importance of histamine in immune responses. However, since a majority of previous studies has evaluated the effects of exogenous histamine, it remains largely unknown how endogenously produced histamine is involved in regulation of such kinds of immune responses. Insight into precise roles of histamine in the immune system can not be obtained without correct understanding of both the predominance of a certain type of histamine receptor and the regulation of histamine synthesis. Here we review a part of the recent progress in histamine research in the field of immunology with attention to the source of involved histamine.

Histamine↗
PubMed1989

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

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

Animals↗
PubMed1979

Metabolic studies on the uptake of [14C]-histidine and [14C]-histamine and histamine synthesis by guinea-pig basophils, in vitro.

The uptake of [14C]-histidine and [14C]-histamine and the conversion of [14C]-histidine to [14C]-histamine was measured in suspensions of guinea-pig bone marrow cells rich in basophils. When comparable amounts of labelled histidine or histamine were added to equal numbers of basophils, the uptake of histidine was approximately forty-five times greater than that of histamine. Purified eosinophils, neutrophils and mononuclear cells incorporated only a small proportion of [14C]-histidine when compared to the basophil; [14C]-histamine uptake by all these cell types was virtually negligible. Histidine uptake and the amount of histamine formed de novo was directly related to the number of basophils, the time of incubation and the substrate concentration. Histidine uptake was decreased by agents which inhibit glycolysis, oxidative phosphorylation, Na + - K + -dependent ATPase, protein synthesis and RNA synthesis. Inhibition was demonstrable in a dose-dependent fashion and at concentrations which had no apparent effect on cell viability. Inhibitors of DNA synthesis, and of microtubule function, had no influence on histidine uptake. Cytochalasin B, an inhibitor of microfilament function, also decreased histidine uptake but only at concentrations previously showen to affect hexose transport. None of the agents tested affected the uptake of [14C]-histamine or the amounts of new histamine formed from the histidine that had been incorporated. These studies suggest that histidine is preferentially incorporated into the basophil; that the uptake depends on the integrity of a number of metabolic pathways, but that once the histidine is taken up these requirements do not apply to the formation of new histamine. In contrast, histamine appeared to diffuse passively, and in relatively small amounts, into all the cell types tested.

Animals↗
PubMed1994

Histamine increases anti-CD3 induced IL-5 production of TH2-type T cells via histamine H2-receptors.

Besides its proinflammatory functions histamine released from basophils and mast cells during immediate-type hypersensitivity reactions is known to inhibit several lymphocyte functions like IL-2 and gamma-IFN production. Recently, it has been shown that T helper cells of type 2 phenotype (TH2) represent the T cell fraction which may play a pivotal role in the promotion of the allergic inflammatory eosinophilic late-phase reaction by secretion of cytokines, especially IL-4 and IL-5. We have investigated the effect of histamine on anti-CD3 induced IL-4 and IL-5 production by TH2 cells. Histamine in concentrations between 10(-7) and 10(-5) mol/l concentration-dependently increased anti-CD3 induced IL-5 production up to 120%, whereas IL-4 production was not affected. The activity of histamine in increasing IL-5 production was mimicked by the H2-receptor agonist dimaprit. Histamine induced increase in IL-5 production was inhibited by histamine H2-receptor antagonists, but remained unaffected by H1- or H3-receptor antagonists. Administration of forskolin which directly stimulates the production of cAMP, the second messenger of the H2-receptor, also resulted in an increase in anti-CD3 induced IL-5 production. These results indicate that the histamine-mediated increase in anti-CD3 induced IL-5 production is mediated via H2-receptors. Consequently, histamine released from mast cells and basophils during the early-phase allergic reaction may act as an important stimulatory signal for the initiation of the allergic inflammatory late-phase reaction by increasing local IL-5 production of allergen triggered TH2 cells.

Animals↗
PubMed1981

The role of central histamine H1- and H2-receptors in hypothermia induced by histamine in the rat.

Histamine administered intraventricularly or into the anterior hypothalamic preoptic region induced dose-dependent hypothermia in rats with chronic i.c.v. cannula. This hypothermia was almost totally abolished by both the histamine H1- and H2-receptor antagonists, mepyramine or chloropyramine and metiamide or cimetidine, respectively, give i.c.v. prior to histamine. In behavioural thermoregulation studies histamine considerably diminished the mean duration of dwelling of the rat under the heat lamp. This effect was abolished by histamine H1- but not by H2-receptor antagonists. It is concluded that histamine induces hypothermia by lowering the set point of the hypothalamic thermostat by means of H1-receptors. Histamine H2-receptor blockers antagonized the increase in tail skin temperature after histamine administration, suggesting that h2-receptors are involved in a heat loss mechanism.

Animals↗
PubMed1994

Histamine inhibits immunoglobulin production via histamine H2 receptors without affecting cell growth in human B cells.

The effect of histamine upon immunoglobulin (Ig) production and proliferation in human B cells was studied. Histamine inhibited Ig production by the human B cell lines IM-9 and CBL in a dose-dependent fashion during 4 days of culture. As little as 10(-5) M was inhibitory. In contrast, proliferation was not affected. Inhibition by histamine was blocked by histamine H2 antagonist, cimetidine, but not by histamine H1 antagonist, diphenhydramine. Moreover, histamine H2 agonist dimaprit inhibited Ig production from B cell lines in a dose-dependent manner, and as little as 10(-8) M was inhibitory. Histamine also inhibited IgM and IgG production by peripheral and tonsillar B cells stimulated with Staphylococcus aureus Cowan strain I and IL-2 without affecting proliferation. This inhibition was also blocked by cimetidine. These results indicate that histamine has a direct inhibitory effect on B cells via histamine H2 receptors, and acts as an immunoregulatory factor.

B-Lymphocytes↗
PubMed1984

Sequential histamine inhalations cause increased bronchial histamine reactivity in guinea pigs: role of platelets, thromboxanes and prostacyclin.

Groups of 6-15 guinea pigs sensitized to ovalbumin were challenged by repeated inhalations of a constant histamine dose at time 0, 10, 20, 60 and 70 min. Bronchial obstruction was measured by whole body plethysmography. The degree of bronchial obstruction increased from one challenge to the other reaching maximal values after 70 min. This increase of bronchial responsiveness to histamine after repeated histamine challenges was reduced by pretreatment with clemastine (histamine H1-receptor antagonist, 0.12 mg/kg i.p., n = 7, P less than 0.05) and more effectively by combined clemastine/cimetidine pretreatment (combined H1-H2-receptor antagonists, 0.12 resp. 10 mg/kg, n = 7, P less than 0.001); pretreatment with acetylsalicylic acid (10 mg/kg orally) accelerated the increase of bronchial responsiveness to histamine (n = 9, P less than 0.01 at the second challenge), inhalation of prostacyclin (1 microgram) prior to each histamine inhalation prevented the increase of bronchial histamine sensitivity totally (n = 10, P less than 0.001), whereas inhibition of thromboxane biosynthesis (imidazol, 10 mg/kg i.p., n = 6; 4-[2-(1H-imidazol-1-yl)ethoxy]benzoic acid, 10 mg/kg i.p., n = 9; imidazo(1,5-a)pyridine-5-hexanoic acid, 1 mg/kg i.p., n = 8) as well as immunologic platelet depletion were ineffective in our test system. We conclude that prostacyclin inhibits the increase of bronchial responsiveness to histamine after sequential histamine inhalation challenges by a platelet independent mechanism. 1-(3-phenyl-2-propenyl)-1H-imidazol, the fourth type of thromboxane synthetase inhibitor tested (10 mg/kg i.p., n = 15) showed specific effects which may be attributed to antihistamine functions.

Animals↗
PubMed1992

In vivo occupancy of histamine H3 receptors by thioperamide and (R)-alpha-methylhistamine measured using histamine turnover and an ex vivo labeling technique.

In the brain, the H3 type of histamine receptor has a pre-synaptic autoreceptor inhibitory role which regulates neuronal release and synthesis of histamine. To examine the interaction of the selective H3 receptor antagonist thioperamide with H3 receptors in the brain in vivo, we have used a functional and non-functional measurement of H3 receptor occupancy. In three species (rat, guinea-pig and mouse) peripheral administration of thioperamide caused dose-related increases in histamine turnover in the cerebral cortex (whole brain was examined in the mouse) and, in the same tissues, inhibited the ex vivo binding of the selective H3 receptor agonist [3H](R)-alpha-methylhistamine ([3H]-RAMH). The peak effect of thioperamide to inhibit ex vivo binding of [3H]RAMH was observed approximately 30 min after i.p. administration, whilst the maximum increase in histamine turnover did not occur until after at least 100 min. At a pretreatment time of 30 min, the ED50 of thioperamide to inhibit ex vivo binding of [3H]RAMH binding in the rat, guinea-pig and mouse brain was found to be 2.0 +/- 0.2, 4.8 +/- 0.6 and 2.6 +/- 0.3 mg/kg (mean +/- SEM, N = 4), respectively. We have also examined the effect of peripheral administration of RAMH on ex vivo binding of [3H]RAMH in rat cortex. Qualitatively and quantitatively similar results to those of thioperamide were observed following i.p. administration of RAMH to rats (ED50 = 3.9 +/- 0.4 mg/kg, mean +/- SEM, N = 4). An effect of RAMH on histamine turnover in rat cortex could not be determined as this compound displayed significant cross-reactivity with the antibodies used in the radioimmunoassay to measure histamine and telemethylhistamine. These data indicate that, following peripheral administration, both thioperamide and RAMH penetrate the brain where they can subsequently interact with H3 receptors. It would appear that binding of thioperamide to H3 receptors is linked with a concomitant increase in histamine turnover in the brain. In conclusion, the ex vivo binding technique, particularly when coupled with measurement of histamine turnover, should provide a valuable means for investigating the ability of any peripherally administered compound to cross the blood-brain barrier and subsequently interact with histamine H3 receptors.

Animals↗
PubMed1998

Antidepressant-like effects of endogenous histamine and of two histamine H1 receptor agonists in the mouse forced swim test.

1. Effects of substances which are able to alter brain histamine levels and two histamine H1 receptor agonists were investigated in mice by means of an animal model of depression, the forced swim test. 2. Imipramine (10 and 30 mg kg(-1), i.p.) and amitriptyline (5 and 15 mg kg(-1), i.p.) were used as positive controls. Their effects were not affected by pretreatment with the histamine H3 receptor agonist, (R)-alpha-methylhistamine, at a dose (10 mg kg(-1), i.p.) which did not modify the cumulative time of immobility. 3. The histamine H3 receptor antagonist, thioperamide (2-20 mg kg(-1), s.c.), showed an antidepressant-like effect, with a maximum at the dose of 5 mg kg(-1), which was completely prevented by (R)-alpha-methylhistamine. 4. The histamine-N-methyltransferase inhibitor, metoprine (2-20 mg kg(-1), s.c.), was effective with an ED50 of 4.02 (2.71-5.96) mg kg(-1); its effect was prevented by (R)-alpha-methylhistamine. 5. The histamine precursor, L-histidine (100-1000 mg kg(-1), i.p.), dose-dependently decreased the time of immobility [ED30 587 (499-712) mg kg(-1)]. The effect of 500 mg kg(-1) L-histidine was completely prevented by the selective histidine decarboxylase inhibitor, (S)-alpha-fluoromethylhistidine (50 mg kg(-1), i.p.), administered 15 h before. 6. The highly selective histamine H1 receptor agonist, 2-(3-trifluoromethylphenyl)histamine (0.3-6.5 microg per mouse, i.c.v.), and the better known H1 agonist, 2-thiazolylethylamine (0.1-1 microg per mouse, i.c.v.), were both dose-dependently effective in decreasing the time of immobility [ED50 3.6 (1.53-8.48) and 1.34 (0.084-21.5) microg per mouse, respectively]. 7. None of the substances tested affected mouse performance in the rota rod test at the doses used in the forced swim test. 8. It was concluded that endogenous histamine reduces the time of immobility in this test, suggesting an antidepressant-like effect, via activation of H1 receptors.

Animals↗
PubMed1992

Functional diversity of histamine and histamine receptors.

In order to analyze the mechanisms by which a single biogenic amine like histamine is capable of inducing a wide variety of both physiologic and pathologic functions in various tissues/cells, histamine responses were dissected in detail from a biochemical and pharmacologic point of view. Histamine is synthesized by multiple isozymes of histidine decarboxylase, and catabolized by either diamine oxidase or histamine-N-methyltransferase. Synthesized intracellular histamine may play a role in cell proliferation, whereas released histamine binds to at least three different histamine-specific receptors, then activates various intracellular components, such as Ca++, cAMP, protein kinase, and ion channels. These second messenger pathways interact differentially with each other in various tissues/cells. Moreover, histamine not only activates its own receptors, but also activates other related receptors such as the serotonin 1c receptor. Therefore, to understand the complex actions of histamine, new approaches should be established, in which multiple phenomena can be monitored simultaneously.

Animals↗
PubMed1978

[Histamine and its role in peptic gastric diseases: the discovery of histamine-H2-receptor antagonists].

For the definition of histamine receptors the following prerequisites must be fulfilled: (1) Course of dose-response curves according to the mass-action law; (2) parallel displacement of these curves to the right in the presence of antagonists; (3) inhibition only by specific histamine antagonists; (4) slope of a Schild-plot not significantly different from unity. For H2-receptors these prerequisites could ideally be fulfilled, especially by the development of highly specific H2-receptor antagonists. However, this new class of compounds acts not only by mere competitive inhibition of histamine at its H2-receptor, but also by activating the metabolism of this secretagogue. A further explanation of the action of H2-receptor antagonists in the treatment of chronic duodenal ulcer may be given by studying the pathogenetic role played by histamine in the development of this disease: duodenal ulcer patients showed an increased liberation of histamine from mucosal mast cell stores as well as a decreased activity of histamine methyltransferase (i. e. longer action of histamine!). The rise in histamine content and histamine methyltransferase activity after vagotomy may be the basis for a biochemical explanation of the acid-reducing effect of this operation.

Animals↗
PubMed1975

The effects of the H1 and H2 antihistamines on "allergic" histamine release and its inhibition by histamine.

Antigen-induced, IgE-mediated release of histamine from human basophiles is an in vitro model of allergic reacttions; it is blocked by extracellular histamine, presumably as a result of its ability to increase adenosine 3',5'-monophosphate (cyclic AMP) levels. The H1 antihistamines do not antagonize these effects of histamine but at approximately equal to 1 mM cause histamine release and at approximately equal to 0.1mM inhibit antigen-induced histamine release. The phenothiazine antihistamines are 10-30 fold more potent inhibitors than the rest; other tricyclic antidepressant drugs share this activity. The mechanism of this inhibition, which occurs in both the 1 degree and 2 degree stages of histamine release, is not known but it is not due to partial agonist activity since the anti-H1 drugs cause a significant fall in cyclic AMP levels. The anti-anaphylactic effects of the H1 antagonists probably play no therapeutic role but we suggest that drugs structurally similar to the phenothiazine antihistamines should be developed for clinical testing. The H2 antihistamines block histamine-induced inhibition of histamine release and the increase in cyclic AMP levels, but neither cause nor inhibit histamine release. The K-B values for the anti-H2 drugs (burimamide approximately equal to 5 muM); metiamide approximately equal to 0.5muM); are similar to those described for other H2 receptors.

Animals↗
PubMed2006

Compared pharmacology of human histamine H3 and H4 receptors: structure-activity relationships of histamine derivatives.

Various histamine derivatives were investigated at the human H3 receptor (H3R) and H4 receptor (H4R) stably expressed in human embryonic kidney (HEK)-293 cells using [125I]iodoproxyfan and [3H]histamine binding, respectively. In Tris buffer, [3H]histamine binding to membranes of HEK(hH4R) cells was monophasic (K(D) of 3.8+/-0.8 nM). In phosphate buffer, the Hill coefficient was decreased (n(H) = 0.5+/-0.1) and a large fraction of the binding was converted into a low-affinity component (K(D) = 67+/-27 nM). The inhibition of [3H]histamine binding by two agonists, a protean agonist and five antagonists/inverse agonists confirms that the potency of many H3R ligands is retained or only slightly reduced at the H4R. Histamine derivatives substituted with methyl groups in alpha, beta or N(alpha) position of the side chain retained a nanomolar potency at the H3R, but their affinity was dramatically decreased at the H4R. With relative potencies to histamine of 282 and 0.13% at the H3R and H4R, respectively, (+/-)-alpha,beta-dimethylhistamine is a potent and selective H3R agonist. Chiral alpha-branched analogues exhibited a marked stereoselectivity at the H3R and H4R, the enantiomers with a configuration equivalent to L-histidine being preferred at both receptors. The methylsubstitution of the imidazole ring was also studied. The relative potency to histamine of 4-methylhistamine (4-MeHA) at the H4R (67%) was similar to that reported at H2 receptors but, owing to its high affinity at the H4R (Ki = 7.0+/-1.2 nM) and very low potency at H1- and H3-receptors, it can be considered as a potent and selective H4R agonist. On inhibition of forskolin-induced cAMP formation, all the compounds tested, including 4-MeHA, behaved as full agonists at both receptors. However, the maximal inhibition achieved at the H4R (approximately -30%) was much lower than at the H3R (approximately -80%). Thioperamide behaved as an inverse agonist at both receptors and increased cAMP formation with the same maximal effect (approximately +25%). In conclusion, although the pharmacological profiles of the human H3R and H4R overlap, the structure-activity relationships of histamine derivatives at both receptors strongly differ and lead to the identification of selective compounds.

Binding, Competitive↗
PubMed2002

Plasma extravasation induced by dietary supplemented histamine in histamine-free mice.

Histidine decarboxylase (HDC) synthesizes endogenous histamine from histidine in mammals. To evaluate the role of histamine in skin allergic reaction, we used HDC gene knockout mice lacking histamine. No plasma extravasation reaction was observed in HDC-/- mice after passive cutaneous anaphylaxis (PCA) test. Compound 48/80, a mast cell granule depletor, produced plasma extravasation inHDC+/+ mice but no extravasation in HDC-/- mice. Interestingly, orally administered histamine was distributed in the skin in HDC-/- mice and in these histamine-supplemented mice the plasma extravasation reaction was observed after the injection of compound 48/80 and the PCA test. Cultured bone marrow-derived mast cells of HDC-/- mice took up histamine from the histamine-supplemented medium into the secretory granules. The absorbed histamine was released in response to the same antigen and antibody combination used as in PCA test. In contrast to the immediate-type response, the delayed-type hypersensitive response, observed as a thickening of the ear skin after trinitrochlorobenzene challenge (following sensitization), showed no differences between HDC+/+ and HDC-/- mice. Therefore, among the allergic skin reactions, histamine is revealed to be an important mediator especially for the plasma extravasation in an immediate-type allergy model.

Animals↗
PubMed1975

Methyl derivatives of histamine; interaction with histamine metabolism.

Several histamine analogs, with ring or side chain methyl groups, were tested for interaction with certain aspects of 14C-histamine metabolism. The physiological catabolite, denoted as 3-methylhistamine under the nomenclature we have adopted, is known to inhibit histamine methylation in vitro and in vivo. At low concentrations, all analogs inhibited histamine methylation by mouse brain homogenates; however 3-methylhistamine was completely ineffective against the highly active enzyme from rat didney, while 2-methylhistamine was most effective. None of the drugs showed a significant effect on in vivo formation of 14C-histamine by mouse stomach. All analogs had a definite effect on the distribution and fate of intravenously injected 14C-histamine. The 2-methyl analog was the strongest in vivo inhibitor of histamine methylation, and 3-methylhistamine next. The side chain N-methylated histamies altered uptake of 14C-histamine in some tissues but inhibited methylation weakly, if at all. Data on blood kidney and urine for 4-methylhistamine were unique, and suggested some effect on tubular reabsorption. 2-methylhistamine may prove to be the inhibitor of choice for in vivo studies on histamine methylation.

Animals↗
PubMed2002

Hemodynamic significance of histamine synthesis and histamine H1- and H2-receptor gene expression during endotoxemia.

The hypothesis that endotoxemia may modify histamine synthesis or histamine receptor expression and that these changes may contribute to cardiovascular dysfunction was tested in rabbits which were rendered endotoxemic by lipopolysaccharide (LPS; 100 micro g/kg, i.v.). The plasma histamine concentration was elevated shortly after LPS, remaining elevated (a 50-fold increase) over the experimental period of 6 h. The sustained increase in plasma histamine was associated with a time-dependent increase in expression of histidine decarboxylase (HDC) in different tissues including atrium, as determined by Western blot analysis. The H(1)-receptor antagonist diphenhydramine significantly shortened the duration of the initial hypotension and the H(2)-receptor antagonist ranitidine greatly suppressed the lasting tachycardia following LPS injection. Northern blot analysis showed that LPS dramatically induced gene expressions of histamine H(1)- and H(2)-receptors in cardiac tissues. In right atrium isolated from the septic animal, the positive chronotropic effect of histamine was significantly diminished. This was possibly due to a marked reduction in G(s)(alpha) protein expression, indicating the impaired H(2)-receptor cellular signaling. In conclusion, LPS-induced endotoxemia causes prominent increases in production of histamine through induction of HDC and in gene expression of histamine receptors. We suggest that overproduction of histamine may be partly responsible for the hemodynamic alterations of endotoxemia.

Animals↗
PubMed1990

Does intracellular histamine mediate mast cell histamine release?

Previously, we demonstrated that through binding a novel intracellular receptor of microM affinity (HIC), histamine mediates, and the HIC antagonist N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine. HCl (DPPE) inhibits, platelet aggregation and serotonin granule secretion; the latter response is dependent upon the same processes that mediate histamine release from mast cell granules. We now show that, as for platelet serotonin release, DPPE blocks concanavalin A-stimulated mast cell histamine release with a potency (IC50 = 30 microM) greater than the H1-antagonist, pyrilamine (IC50 = 150 microM) or the H2-antagonist cimetidine (IC50 = 5 mM), correlating with rank order of potency to inhibit 3H-histamine binding in rat brain membranes and liver microsomes. We postulate that histamine release from mast cells is mediated at HIC by second messenger intracellular histamine. However, unlike platelets, mast cells do not appear to rely on newly synthesized histamine. Rather, as for calcium, histamine may be mobilized from bound stores to mediate histamine secretion.

Animals↗