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At least 19 recordsLinked to original sources

PubMed1995

Histamine receptor-dependent and/or -independent activation of guanine nucleotide-binding proteins by histamine and 2-substituted histamine derivatives in human leukemia (HL-60) and human erythroleukemia (HEL) cells.

In dibutyryl cAMP-differentiated human leukemia (HL-60) cells, the potent histamine H1-receptor agonist, 2-(3-chlorophenyl)histamine, activates pertussis toxin (PTX)-sensitive guanine nucleotide-binding proteins (G-proteins) of the Gi-subfamily by a mechanism which is independent of known histamine receptor subtypes (Seifert et al. Mol Pharmacol 45: 578-586, 1994). In order to learn more about this G-protein activation, we studied the effects of histamine and various 2-substituted histamine derivatives in various cell types and on purified G-proteins. In HL-60 cells, histamine and 2-methylhistamine increased cytosolic Ca2+ concentration ([Ca2+]i) in a clemastine-sensitive manner. Phenyl- and thienyl-substituted histamines increased [Ca2+]i as well, but their effects were not inhibited by histamine receptor antagonists. 2-Substituted histamines activated high-affinity GTPase in HL-60 cell membranes in a PTX-sensitive manner, with the lipophilicity of substances increasing their effectiveness. Although HEL cells do not possess histamine receptors mediating rises in [Ca2+]i, 2-(3-bromophenyl)histamine increased [Ca2+]i in a PTX-sensitive manner. It also increased GTP hydrolysis by Gi-proteins in HEL cell membranes. All these stimulatory effects of 2-substituted histamine derivatives were seen at concentrations higher than those required for activation of H1-receptors. In various other cell types and membrane systems, 2-substituted histamine derivatives showed no or only weak stimulatory effects on G-proteins. 2-Substituted histamine derivatives activated GTP hydrolysis by purified bovine brain Gi/Go-proteins and by pure Gi2 (the major PTX-sensitive G-protein in HL-60 and HEL cells). Our data suggest the following: (1) histamine and 2-methylhistamine act as H1-receptor agonists in HL-60 cells; (2) incorporation of bulky and lipophilic groups results in loss of H1-agonistic activity of 2-substituted histamine derivatives in HL-60 cells but causes a receptor-independent G-protein-stimulatory activity; (3) the effects of 2-substituted histamine derivatives on G-proteins are cell-type specific.

Animals↗

PubMed1979

The effect of histamine-1 and histamine-2 antagonists on airway responses to histamine in the rhesus monkey.

This study used rhesus monkeys with consistent respiratory responses to aerosolized histamine. Two systems of histamine challenge were evolved to study the effects of histamine antagonists on the histamine-induced respiratory response. One system consisted of administering increasing subreactive concentrations of histamine until an airway response (H) occurred. This threshold histamine dose was repeated (H'). The pulmonary function changes occurring with the H' challenge were less intense than those with H. M, a histamine-2 receptor antagonist, when given before the H' dose was associated with a potentiated H' response compared with the threshold H response. This provides evidence for histamine-2 receptor sites in rhesus monkey airways. A second system used duplicate histamine challenges with a known reactive dose of histamine. In this system, the pulmonary function changes occurring with the repeated challenge (H') were greater than with the first reactive challenge dose (H). This H' response was inhibited partially with diphenhydramine, a histamine-1 receptor antagonist. These two systems of histamine challenge provide an experimental model for evaluating pharmacologic alteration of histamine-induced respiratory responses. There is evidence for the existence of histamine-1 and histamine-2 receptor sites in the airways of the rhesus monkey.

Animals↗

PubMed2001

Dynamics of histamine H(3) receptor antagonists on brain histamine metabolism: do all histamine H(3) receptor antagonists act at a single site?

Thioperamide, the prototypical histamine H(3) receptor antagonist, acts at the brain histamine H(3) autoreceptor to promote the release and metabolism of neuronal histamine, resulting in higher brain levels of the metabolite tele-methylhistamine. However, unlike thioperamide, several new histamine H(3) receptor antagonists enter the central nervous system (CNS), block brain histamine H(3) receptors and increase histamine release without increasing brain tele-methylhistamine levels. Experiments were performed presently in an attempt to understand these results. Consistent with previous findings, thioperamide significantly increased the content and synthesis rate of tele-methylhistamine in mouse and rat brain. In contrast, the histamine H(3) receptor antagonists GT-2227 (4-(6-cyclohexylhex-cis-3-enyl)imidazole) and clobenpropit did not affect tele-methylhistamine synthesis rate in mouse whole brain. The histamine H(3) receptor ligand GT-2016 (5-cyclohexyl-1-(4-imidazol-4-ylpiperidyl)pentan-1-one) had no effect on tele-methylhistamine levels in any rat brain region and decreased tele-methylhistamine synthesis rates in the mouse whole brain. To examine the possibility that these histamine H(3) receptor antagonists might prevent the methylation of newly released histamine, they were co-administered with thioperamide to determine their effects on the thioperamide-induced stimulation of tele-methylhistamine synthesis. GT-2016 significantly reduced the thioperamide-induced activation of tele-methylhistamine synthesis in mouse whole brain and in several regions of rat brain. Although further clarification is needed, these results suggest that some histamine H(3) receptor antagonists may promote the release of neuronal histamine, but also act to reduce histamine methylation in vivo by an unknown mechanism.

Analysis of Variance↗

PubMed1996

Interaction between the two signal transduction systems of the histamine H2 receptor: desensitizing and sensitizing effects of histamine stimulation on histamine-dependent cAMP production in Chinese hamster ovary cells.

The histamine H2 receptor is a member of the family of G-protein-coupled receptors and is linked to the activation of adenylate cyclase phospholipase C (PLC). In this study we examined the effects of protein kinase C (PKC) activation in Chinese hamster ovary (CHO) cells stably expressing canine histamine H2 receptors. Pretreatment with 100 nM phorbol 12-myristate 13-acetate at 37 degrees C for 15 min led to significant potentiation of histamine-dependent and forskolin-dependent cAMP production, whereas the biologically inactive phorbol ester, 4 alpha-phorbol 12, 13-didecanoate, was without effect. These potentiating effects were abolished by preincubation with 0.5 microM bisindolylmaleimide, a PKC inhibitor. Thus the activation of PKCs seems to be involved in the potentiation of cAMP production by acting on a post-receptor mechanism. Preincubation of a CHO cell line, CHO-H2R, with 10 microM histamine for 30 min had two effects. Maximal histamine-dependent cAMP production and forskolin-dependent cAMP production were potentiated by 36% and 105.2% respectively. The other effect was a desensitization of the histamine-dependent adenylate cyclase response as demonstrated by a three-fold increase in EC50. Administration of 0.5 microM bisindolylmaleimide before preincubation of CHO-H2R with 10 microM histamine did not alter the desensitizing effect on cAMP production, but did abolish the sensitizing effect. Preincubation of CHO-H2R cells with 10 nM histamine resulted in moderate potentiation, which was also abolished by bisindolylmaleimide, but not in desensitization of the histamine-dependent cAMP production. Thus these results suggest that preincubation with histamine had a sensitizing effect on cAMP production mediated by PLC and PKC activation, as well as a desensitizing effect on the H2 receptor. The former effect is dependent on the intensity of PLC and PKC signals delivered by H2 receptors. The latter effect requires a higher concentration of histamine.

Animals↗

PubMed2002

Real-time monitoring of histamine released from rat basophilic leukemia (RBL-2H3) cells with a histamine microsensor using recombinant histamine oxidase.

To detect low levels of histamine, we developed a histamine microsensor using recombinant histamine oxidase. Histamine oxidase with a histidine tag was readily purified using a histidine affinity column. The enzyme showed higher catalytic activity on histamine than diamines (e.g., putrescine and cadaverine) or N(tau)-methylhistamine. The sensor had three carbon film electrodes modified with osmium-polyvinylpyridine-based gel containing horseradish peroxidase, histamine oxidase, and Ag. When a standard solution of histamine was aspirated at a flow rate of 2 microl/min, the detected current was proportional to the histamine concentration and the lower detection limit was 11.3 nM. When rat basophilic leukemia cells (1 x 10(6)) were stimulated by various concentrations of antigen (2, 20, and 200 ng/ml), the histamine concentrations were 0.32, 2.7, and 1.3 microM, respectively, and 20 ng/ml of antigen was found to be the optimal concentration for the antigen-antibody reaction. In contrast, when thapsigargin, an inhibitor of Ca-ATPase in the endoplasmic reticulum, was added (50, 100, and 500 nM), the detected current increased with thapsigargin concentrations and the measured histamine concentrations were 28 nM, 1.3 microM, and 2.7 microM, respectively. These results indicate that the microsensor is useful for the analysis of histamine release from mast cells.

Amine Oxidase (Copper-Containing)↗

PubMed1993

Measurement and characterization of histamine and methylhistamine in human urine under histamine-rich and histamine-poor diets.

A radioimmunoassay for histamine was used to measure histamine and 1-methylhistamine (MH) in human urine samples. The detection limit of this assay was 2 ng/ml for histamine and 0.5 ng/ml for MH. Cation exchange high performance liquid chromatography (HPLC) on a Bio-Gel TSK SP-5 PW column with gradient elution was capable of separating histamine from its precursor L-histidine and its metabolites MH and 1-methylimidazole acetic acid (MIAA). The concentration of MH-immunoreactive materials in healthy volunteers with no dietary restrictions was 202 +/- 92 micrograms/24 h (mean +/- SD; n = 14). The excretion of MH-like material, expressed as micrograms of MH per 24 h, was not significantly different before or after the intake of histamine-rich food: 217 +/- 88 vs. 276 +/- 135 micrograms/24 h (n = 10). However, in urine samples collected in individual fractions, the levels of MH immunoreactivity were significantly increased after a histamine-rich meal in comparison to the corresponding fractions which were taken a day earlier at the same time intervals after a histamine-low diet (p < 0.03). HPLC characterization of MH immunoreactivity revealed the presence of histamine, MH and a compound with the same retention time as MIAA. The ratio of histamine, MH and MIAA in controls without dietary restrictions, as determined by HPLC analysis, was 50 +/- 6, 47 +/- 5 and 3 +/- 1%, respectively. After a histamine-rich meal the ratio was 97 +/- 2% for histamine, 1% for MH and 2 +/- 1% for MIAA.

Adult↗

PubMed1978

Histamine enhances anaphylactic histamine release from bovine lung and leukocytes via histamine H2-receptor.

Chopped lung and isolated leukocytes of calves sensitized to horse plasma release histamine when incubated with the antigen. Low concentrations (10(-9) and 10(-8) M) of exogenous histamine enhanced both spontaneous and antigen-induced histamine release. The enhancement of antigen-induced histamine release was inhibited by metiamide but not by mepyramine, whereas the enhancement of spontaneous histamine release was not significantly affected by either histamine antagonist. At higher concentrations of exogenous histamine (10(-6) to 10(-4) M), uptake and metabolism significantly interfered with the method. These results indicate the existence in bovine lung and leukocyte of a positive feedback mechanism which regulates histamine release via an H2-receptor. This is in direct contrast to the reported situation in the human leukocyte, and suggests that histamine fulfils an important role in the intrinsic control of allergic reactions in cattle.

Anaphylaxis↗

PubMed1997

Binding of histamine H3-receptor antagonists to hematopoietic progenitor cells. Evidence for a histamine transporter unrelated to histamine H3 receptors.

Hematopoietic progenitor cells can take up histamine or release IL-3-induced histamine through a bi-directional transport system that is blocked by H3-receptor antagonists. In the present study we demonstrate a correlation between the affinity of various H3-receptor antagonists and their potency as inhibitors of histamine uptake. All compounds that blocked histamine uptake also inhibited IL-3-induced histamine release. Yet, classical H3 receptors are not involved in this biological activity, since highly specific histamine H3-receptor agonists neither alter histamine uptake nor affect the release of endogenous histamine synthesized in response to IL-3. Furthermore, the inhibitory effect of H3-receptor antagonists on histamine uptake was not reversed by the agonists. Unlike H3-receptor antagonists, the agonists did not displace the binding of the labeled antagonist iodoproxyfan.

Animals↗

PubMed1999

Nalpha-methyl histamine and histamine stimulate gastrin release from rabbit G-cells via histamine H2-receptors.

BACKGROUND: Gastrin release by Helicobacter pylori may be an important step in the pathway leading to duodenal ulceration. A histamine H3-receptor agonist was found to release gastrin from antral mucosal fragments; this was interpreted as being due to suppression of somatostatin release. H. pylori is reported to produce Nalpha-methyl histamine (NalphaMH), which is an agonist of H3 as well as other histamine receptors. H. pylori infection also recruits mast cells, which release histamine. AIM: To determine the direct effects of histamine receptor agonists on isolated gastrin cells. METHODS: Rabbit G-cells were prepared by countercurrent elutriation and cultured on 24-well plates. RESULTS: NalphaMH (10-6-10-4 M) caused a dose-dependent increase in gastrin release from a basal level of 2.3 +/- 0.2% total cell content (TCC; mean +/- S.E.M.) to a maximum of 5.1 +/- 0.7%, an increase of 117% (P < 0. 005) above basal. This was abolished by the H2-antagonist ranitidine (10-5 M), but not by immunoblockade with anti-somatostatin antibody, the H1-antagonist chlorpheniramine (10-5 M) or the H3-antagonist thioperamide (10-4 M). The histamine H2-receptor agonist dimaprit (10-6-10-4 M) increased gastrin release from 2.4 +/- 0.2% to 3.6 +/- 0.2% TCC (P < 0.001). Gastrin release was also stimulated by histamine (10-7-10-4 M) from a basal value of 3.0 +/- 0.3% to 5.4 +/- 0.5% TCC (P < 0.001). This also was inhibited by ranitidine (10-5 M) (P < 0.01). CONCLUSION: NalphaMH and histamine release gastrin from G-cells via H2-receptors; this might contribute to H. pylori-associated hypergastrinaemia.

Animals↗

PubMed1982

Histamine as a ligand in blood plasma. Part 5. Computer simulated distribution of metal histamine complexes in normal blood plasma and discussion of the implications of a possible role of zinc and copper in histamine catabolism.

Previously physiological experiments carried out on mice have proved that copper and zinc can interfere with the pharmacological effects of histamine that lead to anaphylactic shock. A quantitative study of the interactions between essential metal ions and histamine in plasma was thus undertaken. The progressive approach towards a reliable computer-simulated distribution of the histamine-containing plasma species necessitated a large series of physicochemical determinations of the formation constants of the binary and ternary metal complexes involved. The present paper deals with the determination of the formation constants in the zinc-serine, zinc-histamine-serine, zinc-histamine-lysine, copper-serine, copper-histamine-serine, and copper-histamine-valine systems, which were still necessary to reach the reliable simulation required. The subsequent final distribution of histamine in plasma has thus been computed, and interpreted in terms of a possible role for zinc in assisting the histamine catabolism process. Further computer calculations simulating the increase of the zinc concentration in human blood plasma support this interpretation. The antagonizing role of copper against that of zinc has also been examined.

Animals↗

PubMed2002

[Histamine receptors in the female reproductive system. Part II. The role of histamine in the placenta, histamine receptors and the uterus contractility].

The presence of the mast cells was confirmed not only in the uterus but also in the placental tissue. Mediators released from the placental mast cells may play a role in regulation of placental blood flow and normal blood pressure. Processes such uptake and clearance of vasoactive mediators may be upset in those women who developed pre-eclampsia. Histamine released from the placental mast cells may be involved in the mechanisms controlling myometrium contractility during the labour at term and preterm delivery. There is a correlation between the level of placental histamine and presence (or not) uterus contractility. Histamine produce a contractile response in isolated myometrial strips, in the majority of mammals, via H1 histamine receptors activation, but in some species e.g. rat, predominant response of uterus is relaxation (via H2 histamine receptors activation). Predominant response of the human uterus to histamine is contraction. Relaxation of human myometrial strips may be evoked after earlier usage of H1 receptors antagonists, although some H2 receptors agonists (e.g. dimaprit) induce the relaxation of human uterus without H1 receptors antagonists. Myometrium contractile activity is under control of sexual hormones. Neither the presence of H3 histamine receptors on the human myometrial smooth cells nor its role in the female reproductive system regulation was proved. Lack of the functional H3 receptors either on the smooth muscle cells or neuronal components of the animals' myometrium was shown in some studies.

Animals↗

PubMed1991

Comparison of methods for intestinal histamine application: histamine in enterosoluble capsules or via a duodeno-jenunal tube. Influence of fast and histamine-restrictive diet.

The study was conducted to investigate whether introduction of histamine in enterosoluble capsules produced the same amount of urinary histamine metabolites as that found after application of histamine through a duodeno-jejunal tube. Secondly, to examine whether a histamine-restrictive or a fast diet affected the amount of urinary metabolites. Fifteen healthy subjects were challenged four times with 100 mg of histamine. Results were monitored by the urinary recovery of 1,4-methylimidazole acetic acid (MIAA) from 24 h before to 72 h after challenge. Urine was collected in 24-h samples except on the first day after challenge when separation into 0-2h-, 2-4 h- and 4-24 h-fractions was made. MIAA was measured by high performance liquid chromatography (HPLC). The results showed that during the first 2 h after challenge the recovery of MIAA was higher with tubes than with capsules. Measurements from all other intervals did not differ significantly between the two challenge regimens. Fast (water only) and histamine-restrictive diet versus non-restrictive diet did not affect the urinary MIAA. MIAA was significantly higher overall during the first 24 h after challenge than in any other fraction. We conclude that oral administration of enterosoluble capsules is an easy and appropriate method for intestinal histamine challenge. Fast and histamine-restrictive diets are not necessary, but subjects should record unexpected responses in a food and symptom diary.

Adolescent↗

PubMed1982

Histamine as a ligand in blood plasma. Part 6. Aspartate and glutamate as possible partner ligands for zinc and histamine to favour histamine catabolism.

The hypothesis was recently put forward that the diffusion of plasma histamine into the environmental tissues in which the mediator is catabolized, may occur passively in the form of the zinc-histamine-cysteinate complex. In accordance with this hypothesis, any partner ligand for zinc and histamine in which raising plasma concentration would entail a better mobilization of histamine into neutral diffusable metal complexes would also favour the histamine catabolism. Such a role was envisaged in the present work for aspartate and glutamate. Their efficiency in that respect was tested on the basis of computer simulations using the equilibrium constants of the corresponding zinc-histamine-aspartate and zinc-histamine-glutamate complexes, which were determined beforehand under the plasma conditions of temperature, ionic strength and isotonicity. It was established that aspartate and glutamate plasma concentrations should be raised 1000 and 400 times over their respective normal levels before the combination of each of these amino-acids with zinc within the same increase ratio becomes more efficient than zinc ions alone.

Aspartic Acid↗

PubMed1985

[Histamine receptor-bearing lymphocytes. III. Suppression of immune reactions by killing of histamine receptor-bearing lymphocytes with a conjugate of histamine and the A chain of mistletoe lectin I].

Conjugates of the A-chain of the mistletoe lectin I and histamine but not A-chain per se inhibit the capacity of spleen cells of the mouse to induce antibody response or graft-versus-host reaction by 90%. The conjugates killed 27% of the spleen cells, 60% of the T-, and 15% of the B-lymphocytes. The receptors for histamine could be shown to be of the H2-type, because only H2-antagonists inhibited the toxic influence of the conjugates. The results suggest the hypothesis that not only suppressor cells but at least the majority of the immunocompetent cells bear receptors for histamine. The A-chain-histamine conjugate represents an "affinotoxin" which is cytotoxic only after affinity binding on receptors of the target cell.

Animals↗

PubMed1983

Histamine release into tracheal lumen and bronchial reactivity. Effect of local histamine administration on histamine release and bronchial reactivity.

The influence of tracheal lavage with histamine, and of i.v. administration of histamine on bronchospastic response was studied in 16 dogs. Airway response to acetylcholine inhalation was significantly increased after tracheal lavage with high concentrated histamine solution (1%). No influence on airway response was found after (1) tracheal lavage with lower concentrations of histamine and (2) its i.v. administration. The clinical importance of these manifestations is discussed.

Acetylcholine↗

PubMed1980

Regulation of histamine synthesis: altered synthesis and level of histamine in the hypothalamus of rats by repeated administration of histamine H1 and H2 receptor antagonists.

Repeated administration of histamine H1 and H2 receptor antagonists resulted in significant alterations in the hypothalamic histamine level of rats and similar changes in the HD activity of the hypothalami were observed after these treatment. The changes in the level run parallel with the modifications in the HD activity. The effects of classical antihistaminergic agents were however opposite to that of the specific H2 antagonists, namely chloropyramine and tripelennamine markedly enhanced while metiamide and cimetidine diminished the hypothalamic level of histamine.

Adenylyl Cyclases↗

PubMed1987

Histamine H1 receptors on adherent rheumatoid synovial cells in culture: demonstration by radioligand binding and inhibition of histamine-stimulated prostaglandin E production by histamine H1 antagonists.

Histamine H1 receptors have been demonstrated on adherent rheumatoid synovial cells using biochemical and radioligand binding assays in vitro. The addition of histamine (17.8 mumol/l) to nine primary cultures of adherent rheumatoid synovial cells resulted in a two- to 21-fold increase in the production of prostaglandin E (PGE). This increase was inhibited by three H1 receptor antagonists (mepyramine, tripelennamine, and chlorpheniramine) in a dose related manner at concentrations below 10(-6) mol/l. Competitive binding assays with [3H]mepyramine gave ED50 values of approximately 10(-5) mol/l for the three H1 antagonists. H2 receptor antagonists (cimetidine and ranitidine) did not inhibit the histamine induced increase in PGE and did not compete effectively with the binding of H1 antagonists.

Arthritis, Rheumatoid↗

PubMed1983

Histamine is able to suppress the inhibitory effect of somatostatin on exogenous gastrin: comparison between extractive antral histamine and synthetic histamine.

In view of examining inhibition by somatostatin of gastrin-induced gastric secretion, antral histamine (AH) and synthetic histamine (SH) were comparatively studied in dogs. Both AH and SH were able to antagonize somatostatin: their potencies did not differ significantly as regards acid secretion, but AH is more potent than SH on pepsin secretion. The dose-dependent activity of AH was limited for the period of infusion. The denervated pouch is more sensitive than the innervated stomach. We suggest that antral histamine might intervene in the complex regulation of gastric secretion where somatostatin and gastrin act antagonistically and where the stimulatory as well as inhibitory fibers of the vagus intervene.

Animals↗