Possible Involvement Of Histamine Research Articles

Gastritis and peptic ulcers are associated with the lower levels of plasma lipids: possible involvement of histamine

Background: Histamine receptors are involved to regulate lipid metabolism, so the hypothesis will arise that pathological states with abnormal histamine levels are associated with altered plasma lipids. Objectives: To study the profile of plasma lipids in patients with gastritis and peptic ulcer (GPU). Methods: In a case-control study, 70 dyspeptic patients were selected according to clinical criteria and using gastroduodenoscopy and compared with sex and age matched normal subjects. Results: There were no significant differences in age, sex, and the prevalence of hypertension and diabetes between two groups. But allergy, the familial history of allergy and dyspeptic and H. pylori infection were more prevalent in case group compared with controls. The levels of the indices of inflammation and body hydration were the same in two groups. Patients with dyspeptic compared with the controls had the lower concentrations of serum triglyceride (139.2±44.3 vs. 153.4±91.3), p≤0.553), total cholesterol (174.6±32.4 vs. 192.8±52.0, p≤0.073, LDLc (93.4±20.2 vs. 105.4±32.2, p≤0.015) and NonHDLc (130.2±38.1 vs. 159.2±42.2, p≤0.008). The level of HDL had not a significant change (43.4±7.8 vs. 43.5±12.7, p≤0.930). Dyspeptic state had negative significant correlation with total cholesterol, LDLc and NonHDLc but not HDLc. Neither the markers of inflammation nor the indices of body hydration had significant correlation with GPU. Conclusions: The GPU patients relative to normal group had the lower levels of serum lipids. The hypolipemic effects may be attributed to increased level of histamine in GPU patients.

Histamine and diabetic nephropathy: an up-to-date overview.

The classification of diabetic nephropathy (DN) as a vascular complication of diabetes makes the possible involvement of histamine, an endogenous amine that is well known for its vasoactive properties, an interesting topic for study. The aim of the present review is to provide an extensive overview of the possible involvement of histamine in the onset and progression of DN. The evidence collected on the role of histamine in kidney function together with its well-known pleiotropic action suggest that this amine may act simultaneously on glomerular hyperfiltration, tubular inflammation, fibrosis development and tubular hypertrophy.

Distribution of histaminergic neurons and their modulatory effects on oscillatory activity in the olfactory center of the terrestrial slug Limax.

Terrestrial mollusks can form an odor aversion memory following the simultaneous presentation of a food odor and an aversive stimulus. The local field potential oscillation recorded on the surface of the procerebrum (PC; the higher olfactory center) exhibits a frequency change in response to the detection of a learned odor; such a change is thus considered to reflect the internal state of the brain during memory recall. Thus far, dopamine and serotonin have been demonstrated to change the oscillatory frequency. Other monoamines, however, have not yet been studied. In the present study, we investigated the possible involvement of histamine (HA). Immunohistochemical staining of HA and in situ hybridization against histidine decarboxylase revealed the location of the cell bodies of HAergic neurons in all ganglia of the brain. The majority of them were located at the medial aspect of the pedal ganglia, and the cerebral ganglia also contained numerous HAergic neurons in their posterior regions. The neuropil layers of the PC received HAergic innervation from the neurons in the cerebral ganglion, as well as from a few neurons located in the dorsomedial part of the cell mass layer of the PC. The HAergic fibers, however, innervated spatially limited regions of the PC, and seemed to affect a small fraction of the PC neurons. HA exerted accelerating effects on the LFP oscillation in a dose-dependent manner, and this effect was suppressed by an H2 blocker, cimetidine. Our results support the involvement of HA in the functioning of the PC.

Protective effects of histamine on Gq-mediated relaxation in regenerated endothelium

In the porcine coronary artery, regenerated endothelium is dysfunctional as regards the responses to endothelium-dependent agonists. The current study aimed to determine the possible involvement of histamine in such dysfunction. Pigs were treated chronically with pyrilamine (H1 receptor inhibitor, 2 mg·kg(-1)·day(-1)) with part of their coronary endothelium and allowed to regenerate for 28 days after balloon denudation. The results showed a reduction in relaxation to bradykinin (Gq protein dependent) only in the pyrilamine-treated group (area under the curve, 269.7 ± 13.4 vs. 142.0 ± 31.0, native endothelium vs. regenerated endothelium) but not in the control group (253.0 ± 22.1 vs. 231.9 ± 29.5, native endothelium vs. regenerated endothelium). The differences in the relaxation to serotonin (Gi protein dependent) between native and regenerated endothelium were not affected by the pyrilamine treatment (control group, 106.3 ± 17.0 vs. 55.61 ± 12.7; and pyrilamine group, 106.0 ± 8.20 vs. 49.30 ± 6.31, native endothelium vs. regenerated endothelium). These findings indicate that during regeneration of the endothelium, the activation of H1 receptors by endogenous histamine may be required to maintain the endothelium-dependent Gq protein-mediated relaxation to bradykinin, suggesting a beneficial role of the monoamine in the process of endothelial regeneration.

Smoking influences salivary histamine levels in periodontal disease

Histamine, a potent vasoactive amine, is increased in saliva of periodontitis patients. The present study aimed to further investigate the diagnostic potential of histamine for periodontal disease and assessed smoking, a major risk factor of periodontitis, as a possible influencing factor. Salivary and serum samples of 106 participants (60 periodontitis patients, 46 controls) were collected. Salivary histamine was determined by a commercially available ELISA kit, and serum C-reactive protein was measured by a routine laboratory test. Cigarettes per day and packyears were assessed as smoking exposure parameters. Statistically significantly increased levels of salivary histamine and serum C-reactive protein were detected between the patient and control group (P = 0.022 and P = 0.001). Salivary histamine levels were significantly higher in smoking compared with non-smoking patients (P < 0.001), and salivary histamine as well as serum C-reactive protein correlated significantly positively with smoking exposure parameters (P < 0.05). Smoking, an established and common risk factor of periodontitis, was assessed as a possible influencing factor for salivary histamine. Most interestingly, salivary histamine differed highly significantly between smoking and non-smoking periodontitis patients. Our results suggest a possible involvement of histamine in tobacco-exacerbated periodontal disease, but do not suggest salivary histamine as a reliable diagnostic marker for periodontitis.

Roles of Histamine in Exercise-Induced Fatigue: Favouring Endurance and Protecting against Exhaustion

Exercise necessitates a large supply of O(2) and nutrients and rapid removal of CO(2) and waste products. Histamine is a regulator of the microcirculation (which performs these exchanges), suggesting a possible involvement of histamine in exercise. Histamine is released from either mast cells or non-mast cells. In the latter, histamine is newly formed via the induction of histidine decarboxylase (HDC) in response to an appropriate stimulus, and it is released without being stored. Here, in mice, we examined the role of histamine or HDC induction in exercise. Prolonged walking (PW) (in a cylindrical cage turned electrically) increased HDC mRNA and HDC activity in quadriceps femoris muscles. Mice given a histamine H1-receptor antagonist [fexofenadine (peripherally acting) or pyrilamine (peripherally and centrally acting)] or an irreversible HDC inhibitor (α-fluoromethylhistidine) displayed less PW endurance than control mice. Ranitidine (H2-receptor antagonist) tended to reduce endurance. Other histamine-receptor (H3 and H4) antagonists had no significant effects on endurance. Mice deficient in HDC or histamine H1-receptors displayed markedly less endurance than control mice, and HDC activity in the quadriceps femoris of H1-deficient mice was rapidly elevated by PW. Fexofenadine significantly reduced the muscle levels of nitric oxide (NO) metabolites and glycogen after PW. The results support the ideas that (i) histamine is involved in protecting against exercise-induced fatigue or exhaustion, (ii) histamine exerts its protective effect via H1 receptors and the ensuing production of NO in skeletal muscle, and (iii) histamine is provided, at least in part, by HDC induction in skeletal muscles during prolonged exercise.

Comparison of Histamine Content in B16F10 Melanoma Cells and Non‐tumorigenic Melan‐A Melanocytes

Based on earlier suggestions for a possible involvement of histamine in certain cancers, we compared previously the expression of the histamine‐forming enzyme, histidine decarboxylase (HDC), in B16F10 murine melanoma cells and non‐cancerous murine Melan‐A melanocytes. Consistent with an up‐regulated endogenous histaminergic system in cancer cells, immunohistochemistry and Western blot analysis for HDC demonstrated markedly greater expression of HDC protein in B16F10 melanoma cells than in the Melan‐A cells. In the present study, we compared the levels of histamine in the two cell types using immunohistochemistry and enzyme immunoassay (EIA). Markedly greater immunofluorescent staining for histamine was observed in B16F10 than in pair‐stained Melan‐A cells. Consistent with these results, histamine levels measured using EIA were 280‐fold higher (p&lt;0.001) in B16F10 (229 +15 pg/mg protein) than in Melan‐A (0.83+0.03 pg/mg protein) cells. Together with previous data, the increased HDC expression and histamine levels within the B16F10 melanoma cells support the presence of a functional, up‐regulated, endogenous histaminergic system in melanoma cells. Further experiments are needed to determine if the up‐regulated endogenous histaminergic system has an important function in melanoma cells to regulate cell migration and invasiveness.

Comparative Expression of Histidine Decarboxylase (HDC) Protein in B16F10 Melanoma Cells and Nontumorigenic Melan‐A Melanocytes

Histamine is a well‐recognized intermediary in many normal biological and pathophysiological processes. Previous research has suggested a possible involvement of histamine in certain cancers. Evidence of an endogenous up‐regulated histaminergic system in diverse cancer cells supports some form of involvement of histamine with tumor cell proliferation. Based on this evidence we tested the hypothesis that cancerous melanoma cells have increased expression of the histamine‐forming enzyme HDC when compared to normal melanocytes. Immunohistochemistry for HDC demonstrated marked expression of HDC in cancerous B16F10 murine melanoma cells. Western blot analysis revealed increased levels of HDC protein expression in the B16F10 cells when compared to non‐cancerous murine Melan‐A melanocytes. Together with previously published data, the increased HDC expression within melanoma cells indicates the presence of an up‐regulated endogenous histaminergic system in these cancerous cells that could act extracellularly or intracellulary to affect cellular signaling pathways. Further experiments are needed to determine if the up‐regulated endogenous histaminergic system has an important function in melanoma cells to regulate cell migration and invasiveness.

Involvement of Histamine Released From Mast Cells in Acute Radiation Dermatitis in Mice

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

Favorable influence of local injury to the endometrium in intracytoplasmic sperm injection patients with high-order implantation failure

Local injury to the endometrium prior to controlled ovarian stimulation may considerably improve implantation rates and pregnancy outcomes in intracytoplasmic sperm injection patients with high-order implantation failure (> or =4 IVF trials and > or =12 transferred embryos).

Escape behavior under tonic inhibitory control of histamine H 2-receptor mediated mechanisms in the midbrain tectum

The dorsal periaqueductal gray matter (DPAG), superior and inferior colliculus have been implicated in the control of defense reactions in the midbrain. Electrical and chemical stimulation of these structures induces escape behavior, usually accompanied by autonomic responses and antinociception. GABA, 5-HT, opioids, excitatory amino acids and neuropeptides have been postulated to participate in the organization of such defensive reactions in the midbrain tectum. However, little attention has been given to a possible involvement of histamine in the generation of such behavior. To examine this issue in the present study, we assessed the effects of injections into the midbrain tectum of histamine and the H 1 and H 2 receptor antagonists, chlorpheniramine and ranitidine on the behavioral manifestations of the defense reaction. The effects of these drugs were also examined on antinociception, which has been considered to be an inherent component of the defense reaction. Thus, the animals were submitted to an open field test and after 30 min, antinociceptive behavior was measured with the aid of the tail-flick test. The results show that histamine reduced exploratory activity without causing motor deficit, as evaluated by the rotarod test. Ranitidine led to a dose-dependent behavioral activation, with clear signs of fear, whereas no apparent effect was observed following injections of chlorpheniramine. Antinociception always followed the escape reaction induced by the H 2 receptor blocker ranitidine. The present results suggest that H 2 receptors may be involved in the control of escape behavior and antinociception following activation of the neural substrates of fear in the midbrain tectum.

Activation of histamine H3 receptors inhibits renal noradrenergic neurotransmission in anesthetized dogs.

To investigate the possible involvement of histamine H(3) receptors in renal noradrenergic neurotransmission, effects of (R)alpha-methylhistamine (R-HA), a selective H3-receptor agonist, and thioperamide (Thiop), a selective H3-receptor antagonist, on renal nerve stimulation (RNS)-induced changes in renal function and norepinephrine (NE) overflow in anesthetized dogs were examined. RNS (0.5-2.0 Hz) produced significant decreases in urine flow and urinary sodium excretion and increases in NE overflow rate (NEOR), without affecting renal hemodynamics. When R-HA (1 microg x kg(-1) x min(-1)) was infused intravenously, mean arterial pressure and heart rate were significantly decreased, and there was a tendency to reduce basal values of urine flow and urinary sodium excretion. During R-HA infusion, RNS-induced antidiuretic action and increases in NEOR were markedly attenuated. Thiop infusion (5 microg x kg(-1) x min(-1)) did not affect basal hemodynamic and excretory parameters. Thiop infusion caused RNS-induced antidiuretic action and increases in NEOR similar to the basal condition. When R-HA was administered concomitantly with Thiop infusion, R-HA failed to attenuate the RNS-induced antidiuretic action and increases in NEOR. However, in the presence of pyrilamine (a selective H1-receptor antagonist) or cimetidine (a selective H2-receptor antagonist) infusion, R-HA attenuated the RNS-induced actions, similarly to the case without these antagonists. Thus functional histamine H3 receptors, possibly located on renal noradrenergic nerve endings, may play the role of inhibitory modulators of renal noradrenergic neurotransmission.

Upregulation of histidine decarboxylase mRNA expression in scleroderma skin

The involvement of histamine in the pathogenesis of systemic sclerosis (SSc) has been suggested. Possible involvement of histamine and histidine decarboxylase (HDC), the synthesizing enzyme for histamine, in the formation of the skin abnormalities in SSc was studied. Skin histamine concentrations in SSc were significantly lower than in normal controls (P < 0.02). In situ hybridization with an HDC probe revealed that the expression of the HDC gene in SSc was greater than in normal controls. The number of cells and the mean grain number per cell expressing HDC mRNA were both significantly greater in SSc than in normal controls (both P < 0.01). These results show a reduction in histamine concentration and an elevated HDC gene expression in SSc skin, indicating an increase in both histamine release and HDC gene expression. The upregulation of histamine turnover appears to be involved in the formation of the skin abnormalities of SSc.

Histamine-induced sensitization of the heat response of canine visceral polymodal receptors

In elucidating the possible involvement of histamine (His) in hyperalgesia to heat, the effects of His on the heat response of testicular polymodal receptors were studied in vitro in canine testis-spermatic nerve preparations. His (100 and 1000 μM) induced discharges >0.5 impulses/s (high-responders) in about one third of units tested. His (≥10 μM) facilitated the heat response irrespective of whether His alone induced substantial excitation, and the magnitude of facilitation at 100 μM did not differ between high- and low-responders (His-induced discharges ≤0.5 impulses/s). Conduction velocity of high-responders at 100 μM (2.2 ± 0.9 m/s, n = 5) was slower on average than that of low-responders (12.9 ± 1.6 m/s, n = 9). The sensitizing effect of His reported in this paper suggests that His plays a role in hyperalgesia.

Virus-induced airway hyperresponsiveness in the guinea-pig: possible involvement of histamine and inflammatory cells.

1. Guinea-pig tracheal contractions by histamine and by the cholinoceptor agonist, arecoline, are significantly enhanced (30% and 20%, respectively), 96 h after intra-tracheal inoculation with Parainfluenza-3 (PI-3) virus. 2. The airway hyperresponsiveness in animals inoculated with virus coincides with a significant increase in the number of broncho-alveolar cells (82%), and in the albumin concentration (121%) in lung lavage fluid, relative to values obtained in guinea-pigs challenged with control solution. 3. The chemiluminescence production by isolated broncho-alveolar cells, obtained from virus-infected guinea-pigs 96 h after inoculation stimulated with PI-3 virus in vitro, is significantly reduced by 42% relative to broncho-alveolar cells obtained from animals inoculated with control solution. This diminution was not specific for stimulation by PI-3 virus since the chemiluminescence production was also significantly reduced by 30% in response to zymosan. 4. Pretreatment of the guinea-pigs with the anti-allergic drugs, oxatomide (2.5 mg kg-1) or nedocromil (2.5 mg kg-1), or the specific H1-histamine receptor antagonist, levocabastine (0.25 mg kg-1), administered intra-peritoneally twice a day for five successive days, inhibits the virus-induced airway hyperresponsiveness, suppresses the influx of broncho-alveolar cells and increase in albumin content, and corrects the reduced chemiluminescence production by broncho-alveolar cells in response to zymosan. 5. In contrast, the cyclo-oxygenase inhibitor, suprofen (5.0 mg kg-1), the 5-HT2 receptor antagonist, ketanserin (0.63 mg kg-1), or the Ca2+ overload blocker, flunarizine (2.5 mg kg-1) do not modify the above mentioned processes. 6. The platelet-activating factor receptor antagonist, WEB 2170 (10 mg kg-1), reduces virus-induced airway hyperresponsiveness and influx of broncho-alveolar cells into the lungs but does not attenuate the increase of albumin in the bronchial lavage fluid. 7. Guinea-pigs nebulized with histamine, twice a day (30 min) during 4 successive days, do not demonstrate an increased airway responsiveness, but instead show tachyphylaxis in response to histamine in vitro. In addition, no influx of inflammatory cells is found in these animals. 8. These results suggest that histamine does not directly increase the responsiveness of the guinea-pig trachea; however, histamine may be involved in a cascade of events leading to airway hyperresponsiveness after a viral infection, a process that could be related to an influx and/or an activation of broncho-alveolar cells after PI-3 virus stimulation.

Brain Regulation of Renin Secretion Involves Central Histaminergic Neurons

The possible involvement of histamine (HA) in the stress-induced increase in plasma renin activity (PRA) was investigated in male rats. Intracerebroventricular (ICV) infusion of histamine (HA; 3.8-60 micrograms) increased PRA dose-dependently, and the Kd (dissociation konstant) of HA was estimated to approximately 30 micrograms. ICV infusion of HA (30 micrograms) as well as 5 min of restraint stress increased plasma renin activity (PRA) 2- and 3-fold, respectively (p less than 0.01). These effects were abolished by prior ICV infusion of the H2-receptor antagonists cimetidine (100 micrograms) and ranitidine (125 micrograms) (p less than 0.01), which reduced the PRA to subbasal levels (p less than 0.05). When administered alone the H2-receptor antagonists had no effect on PRA. In contrast, the H1-receptor antagonist mepyramine (100 micrograms) increased the basal PRA level (p less than 0.01) and slightly augmented the HA- and stress-induced increase in PRA (p less than 0.05). HA as well as restraint stress increased the plasma levels of dopamine, norepinephrine and epinephrine almost 2-fold (p less than 0.01). The effect of the two stimuli was prevented by prior ICV infusion of mepyramine or cimetidine (p less than 0.01). Pretreatment with the beta-adrenergic receptor blocker propranolol (7 mg/kg i.p.) abolished the HA-induced and inhibited by 70% the stress-induced PRA increase. The results indicate that histaminergic neurons participate in the cerebral regulation of renin secretion. The H2-receptor-mediated PRA-increasing effect of HA involves activation of sympathetic nerves. In addition, HA seems to exert a minor inhibiting effect on PRA via H1-receptors.

Histamine is involved in ethanol-induced jejunal microvascular injury in rabbits

To examine for the possible involvement of histamine in the jejunal microvascular effects of ethanol, we investigated the effects of (a) intraluminal ethanol on histamine release by the jejunum and (b) simultaneous inhibition of both histamine1 and histamine2 receptors (using promethazine and cimetidine, respectively) on ethanol-induced intestinal plasma protein loss in rabbits. Ethanol increased histamine release by the jejunum both in vivo (p < 0.01) and in vitro (p < 0.05). To investigate the effect of antihistamines on ethanol-induced plasma protein loss, we determined the dose of blockers that would completely inhibit the histamine1 and histamine2 receptors. In the absence of antihistamines, ethanol caused a 10-fold increase in jejunal protein loss over the controls (p < 0.001). Simultaneous inhibition of histamine1 and histamine2 receptors attenuated (p < 0.025), but did not abolish, the ethanol-induced protein loss. These data are discussed in relation to the literature, and it is concluded that histamine may play a role in the jejunal microvascular effects of ethanol. As the ethanol-induced protein loss was not completely inhibited, other mediators or mechanisms were probably involved.

Histaminergic mediation of the stress-induced release of prolactin in male rats.

Histamine (HA) is likely to participate in the neuroendocrine regulation of prolactin (PRL) secretion. We, therefore, studied the possible involvement of HA in the stress-induced release of PRL in conscious male rats. HA (30 micrograms) infused intracerebroventricularly 15 min before decapitation elevated PRL plasma levels from 5 +/- 1 to 54 +/- 6 ng/ml (p less than 0.01). Intracerebroventricular infusion of the H2 receptor antagonists cimetidine (CIM: 100 micrograms) or ranitidine (RAN: 125 micrograms) abolished the PRL response to HA (p less than 0.01), while intracerebroventricular infusion of the H1 receptor antagonist mepyramine (MEP; 100 micrograms) inhibited the response only 40% (p less than 0.05). Intra-arterial infusion of CIM (2,000 micrograms) or RAN (2,500 micrograms) inhibited the HA-stimulated PRL secretion 52% (p less than 0.01) or 63% (p less than 0.01), respectively. The H1 receptor antagonists MEP (1,000 micrograms) and SKF-93944 (1,500 micrograms) had no effect following intra-arterial administration. Restraint stress increased the PRL level to 84 +/- 6 ng/ml (p less than 0.01 vs. control). This effect was prevented by intracerebroventricular infusion of CIM or RAN (p less than 0.01) and inhibited 75% by MEP (p less than 0.01). Intra-arterial infusion of CIM, MEP, and SKF-93944 inhibited the stress response about 50% (p less than 0.01), while RAN decreased the response only 25% (p less than 0.05). Ether stress elevated the plasma PRL concentration to 46 +/- 5 ng/ml (p less than 0.01 vs. control). When infused intracerebroventricularly CIM or RAN prevented the response (p less than 0.01), while MEP had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Possible involvement of histamine H 2-receptors in the vasodilator effect of clonidine on isolated and perfused canine coronary arteries

The mechanism of clonidine-induced vasodilatation was investigated in the isolated and perfused canine coronary arteries. Clonidine produced a slight vasoconstriction at small doses whereas it induced a dose-related vasodilatation at large doses (more than 3 μg). The vasodilatation was reversed to vasoconstriction by treatment with 100 μg of cimetidine (a selective H 2-receptor antagonist) but was not affected by 100 μg of chlorpheniramine (a selective H 1-receptor antagonist). These result suggest that clonidine can dilate the isolated and perfused canine coronary arteries by acting on histamine H 2-receptors.

Etiopathogenic mechanisms of bronchoconstriction in byssinois--a review.

Studies of etiopathogenic mechanisms of bronchoconstriction in byssinosis indicate the possible involvement of histamine, 5-HT, platelet-activating factor, and metabolites of arachidonic acid as mediators of bronchoconstriction. These substances might be released by a variety of lung and/or recruited cells to induce construction of respiratory airways characteristic of the acute byssinotic reaction. It certainly seems possible that cotton dust induces acute bronchoconstriction by more than one mechanism and that a number of factors, both endogenous and exogenous, influence the increased bronchomotor response to cotton dust inhalation in any given textile worker.