Histamine In Regulation Research Articles

Histamine in regulation of bone remodeling processes

Bone remodeling is under autocrine, paracrine, endocrine and central nervous system control. One of the potential endogenous factors affecting bone remodeling is histamine, an endogenous amine which acts as a mediator of allergic reactions and neuromediator, and induces production of gastric acid. Histamine H₁ receptor antagonists are widely used in the treatment of allergic conditions, H₂ receptor antagonists in peptic ulcer disease, and betahistine (an H₃ receptor antagonist and H₁ receptor agonist) is used in the treatment of Ménière's disease. Excess histamine release in mastocytosis and allergic diseases may lead to development of osteoporosis. Clinical and population-based studies on the effects of histamine receptor antagonists on the skeletal system have not delivered unequivocal results. Expression of mRNA of histamine receptors has been discovered in bone cells (osteoblasts and osteoclasts). Histamine synthesis has been demonstrated in osteoclast precursors. Histamine increases bone resorption both by direct effects on osteoclast precursors and osteoclasts, and indirectly, by increasing the expression of RANKL in osteoblasts. In in vivo studies, H₁ and H₂ receptor antagonists exerted protective effects on the bone tissue, although not in all experimental models. In the present article, in vitro and in vivo studies conducted so far, concerning the effects of histamine and drugs modifying its activity on the skeletal system, have been reviewed.

Histamine is novel endothelium‐derived relaxing factor in rat mesenteric lymphatic vessels

Our recent studies (Nagai et al., 2011) suggested the existence of yet undiscovered, shear‐dependent, but NO‐independent regulatory mechanism in rat mesenteric lymphatic vessels (MLV). In this study we performed for the first time the detailed evaluation of potential involvement of histamine in such regulation of MLV contractility in F‐344 rats of various age groups (3‐mo, 9‐mo and 24‐mo). Using confocal and epifluorescent IHC labeling, we confirmed the presence of histidine decarboxylase (HDC), histamine‐producing enzyme, within the lymphatic endothelial cells in MLV. These results were re‐confirmed by Western blot analysis. Using Vivo‐Morpholino technology we were able to knock‐down effectively HDC protein within MLV. In experiments with isolated MLV, we found that only combined blockade of eNOS (NO production) by L‐NAME and HDC (histamine production) by α‐methyl‐DL‐histidine dihydrochloride was able to completely eliminate all shear‐dependency of lymphatic contractile self‐adjustment during periods of steady increases of imposed flow. Such regulatory role of histamine appears to be not severely altered by aging. Up‐to‐date results shows that histamine is not involved in fast phasic contraction‐generated shear‐dependent contractile regulation. Our data provide ground for new understanding on the role of histamine in regulation of lymphatic function. NIH R01 AG030578, HL094269.

Sleep and allergic disease: A summary of the literature and future directions for research

Atopic diseases, such as asthma and allergic rhinitis, are common conditions that can influence sleep and subsequent daytime functioning. Children and patients with allergic conditions from ethnic minority groups might be particularly vulnerable to poor sleep and compromised daytime functioning because of the prevalence of these illnesses in these groups and the high level of morbidity. Research over the past 10 years has shed light on the pathophysiologic mechanisms (eg, inflammatory mediators) involved in many atopic diseases that can underlie sleep disruptions as a consequence of the presence of nocturnal symptoms. Associations between nocturnal symptoms and sleep and poorer quality of life as a result of missed sleep have been demonstrated across studies. Patients with severe illness and poor control appear to bear the most burden in terms of sleep impairment. Sleep-disordered breathing is also more common in patients with allergic diseases. Upper and lower airway resistance can increase the risk for sleep-disordered breathing events. In patients with allergic rhinitis, nasal congestion is a risk factor for apnea and snoring. Finally, consistent and appropriate use of medications can minimize nocturnal asthma or allergic symptoms that might disrupt sleep. Despite these advances, there is much room for improvement in this area. Asummary of the sleep and allergic disease literature is reviewed, with methodological, conceptual, and clinical suggestions presented for future research.

Skin reactivity to histamine and expression of histamine receptors mRNA in lymphocytes of healthy subjects and non-small-cell lung cancer patients before and after surgery

Histamine modulates an immunological response through stimulation of appropriate receptor—H1R proinflammatory or H2R suppressive The participation of histamine in regulation of an immunological response in the course of neoplastic disease is determined by the expression of particular receptor. The aim of our work was the investigation of the expression of mRNA of two types of histamine receptors in peripheral blood lymphocytes and the evaluation of skin-prick test with histamine in lung cancer patients before and after surgery. The investigation was performed on 15 patients qualified to surgery before and 7–10 days after treatment and on 12 healthy subjects. Reverse transcriptase polymerase chain reaction (RT-PCR) with primers labeled with fluorescent dyes was performed. Intensity of fluorescence was expressed as relative fluorescence units (RFU). The data were analysed using ABI Prism 310 GeneScan collection software Version 3.1. Skin-prick test with histamine was evaluated after 10 min by measuring the diameter of the weal. The expression of H1R and H2R mRNA in healthy subjects was not significantly different in contrast to the lung cancer patients in which a significant prevalence of H2R mRNA expression was observed before surgery and only slightly decreased after ( P<0.001). Skin-prick test—negative in one patient before surgery, after treatment was positive in all patients and the diameter of histamine weal was significantly increased ( P<0.001). One may assume that the prevalence of the expression of H2R mRNA in patients reflects the status of immunosuppression caused by cancer. Since histamine exerts its suppressive activity trough H2R it seems reasonably to include the antagonists of this receptor to the cancer therapy which may restore a relative balance between accessibility of both types of histamine receptors.

Skin reactivity to histamine and expression of histamine receptors mRNA in lymphocytes of healthy subjects and non-small-cell lung cancer patients before and after surgery

Histamine modulates an immunological response through stimulation of appropriate receptor—H1R proinflammatory or H2R suppressive The participation of histamine in regulation of an immunological response in the course of neoplastic disease is determined by the expression of particular receptor. The aim of our work was the investigation of the expression of mRNA of two types of histamine receptors in peripheral blood lymphocytes and the evaluation of skin-prick test with histamine in lung cancer patients before and after surgery. The investigation was performed on 15 patients qualified to surgery before and 7–10 days after treatment and on 12 healthy subjects. Reverse transcriptase polymerase chain reaction (RT-PCR) with primers labeled with fluorescent dyes was performed. Intensity of fluorescence was expressed as relative fluorescence units (RFU). The data were analysed using ABI Prism 310 GeneScan collection software Version 3.1. Skin-prick test with histamine was evaluated after 10 min by measuring the diameter of the weal. The expression of H1R and H2R mRNA in healthy subjects was not significantly different in contrast to the lung cancer patients in which a significant prevalence of H2R mRNA expression was observed before surgery and only slightly decreased after (P<0.001). Skin-prick test—negative in one patient before surgery, after treatment was positive in all patients and the diameter of histamine weal was significantly increased (P<0.001). One may assume that the prevalence of the expression of H2R mRNA in patients reflects the status of immunosuppression caused by cancer. Since histamine exerts its suppressive activity trough H2R it seems reasonably to include the antagonists of this receptor to the cancer therapy which may restore a relative balance between accessibility of both types of histamine receptors.

Hyperleptinemia, Visceral Adiposity, and Decreased Glucose Tolerance in Mice with a Targeted Disruption of the Histidine Decarboxylase Gene

Histamine has been referred to as an anorexic factor that decreases appetite and fat accumulation and affects feeding behavior. Tuberomammillary histaminergic neurons have been implicated in central mediation of peripheral metabolic signals such as leptin, and centrally released histamine inhibits ob gene expression. Here we have characterized the metabolic phenotype of mice that completely lack the ability to produce histamine because of targeted disruption of the key enzyme in histamine biosynthesis (histidine decarboxylase, HDC). Histochemical analyses confirmed the lack of HDC mRNA, histamine immunoreactivity, and histaminergic innervation throughout the brain of gene knockout mouse. Aged histamine-deficient (HDC-/-) mice are characterized by visceral adiposity, increased amount of brown adipose tissue, impaired glucose tolerance, hyperinsulinemia, and hyperleptinemia. Histamine-deficient animals are not hyperphagic but gain more weight and are calorically more efficient than wild-type controls. These metabolic changes presumably are due to the impaired regulatory loop between leptin and hypothalamic histamine that results in orexigenic dominance through decreased energy expenditure, attenuated ability to induce uncoupling protein-1 mRNA in the brown adipose tissue and defect in mobilizing energy stores. Our results further support the role of histamine in regulation of energy homeostasis.

Roles of histamine in regulation of arousal and cognition: functional neuroimaging of histamine H1 receptors in human brain

Brain histamine is involved in a wide range of physiological functions such as regulation of the sleep-wake cycle, arousal, cognition, and memory mainly through interactions with histamine H1 receptors (H1Rs). Neurons producing histamine, histaminergic neurons, are exclusively located in the posterior hypothalamus and transmit histamine to almost all regions of the brain. Histamine H1 antagonists, or antihistamines, often prescribed for treatment of allergic disorders, sometimes induce sleepiness and cognitive deficits. It is understood that the mechanism of such CNS side effects is that antihistamine blocks H1Rs in the brain. The purpose of the present study was to compare the CNS side effects of different antihistamines. Subjective sleepiness was measured using the Stanford Sleepiness Scale (SSS) and psychomotor performance was examined by a tachistoscope testing system in healthy, young, Japanese volunteers (16 males, 20–28 yrs.) before and after oral administration of antihistamines such as fexofenadine (FEX) and cetirizine (CET). Additionally, H1R occupancy by antihistamines was examined by PET with 11C-doxepin in 8 volunteers. The results of SSS and psychomotor tests demonstrated that FEX tended to be less sedative than CET though the difference was not statistically significant. PET measurements revealed that no H1Rs in the cerebral cortex were occupied by FEX while about 30% of H1Rs were occupied by CET. In summary, it was confirmed that histamine and H1Rs are involved in maintaining arousal and cognition in humans, and that the severity of clinical symptoms is correlated to the amount of antihistamine that penetrated into the brain.

Regulation of interleukin-6, and macrophage colony-stimulating factor mRNA levels by histamine in stromal cell line (MC3T3-G2/PA6).

The aim of this study was to examine the role of histamine in regulation of IL-6 and M-CSF gene expression in bone marrow stromal cells. Total cellular synthesis was also estimated for IL-6. The effects of the amine were evaluated using the stromal cell line, MC3T3-G2/PA6 (PA6). Histamine caused a distinct accumulation of IL-6 mRNA in the cells, whereas it decreased M-CSF transcripts. Both pyridylethylamine, a H1 agonist, and dimaprit, a H2 agonist, caused a large increase in the level of IL-6 mRNA in PA6 cells. The histamine-induced expression of IL-6 mRNA was associated with enhanced secretion of IL-6, as determined by ELISA. These results, together with the results of our previous studies, suggest that histamine produced by stromal macrophages differentially regulates the production of IL-6 and M-CSF in other kinds of stromal cells and hence promotes differentiation and/or proliferation of hematopoietic progenitor cells.

Histamine in cerebrospinal fluid of children with febrile convulsions.

Febrile convulsions (FC) are frequent acute neurologic disturbances of childhood. The cellular and neurochemical mechanisms causing FC are unclear. Among other mechanisms, the CNS histamine (HA) has been suggested to participate in seizure control and thermoregulation. We evaluated the possible role of HA in regulation of FC by measuring HA and tele-methylhistamine (t-MH) concentrations in the cerebrospinal fluid (CSF) of children with FC. The study group consisted of 35 children treated for acute FC in the hospital. The control groups consisted of (a) feverish children without seizures (n = 23), (b) convulsive children without fever (n = 7), and (c) children with neither fever nor convulsions (n = 21). HA was assayed by high-performance liquid chromatography (HPLC) with fluorescence detection, and t-MH was measured by gas chromatography-mass spectrometry. CSF HA concentration in the group of febrile children without seizures was significantly higher (0.69 +/- 0.16 pmol/ml, mean +/- SE) than in children with FC (0.36 +/- 0.07 pmol/ml, p < 0.05, analysis of variance, ANOVA). HA concentration was 0.37 +/- 0.18 pmol/ml in the group of nonfebrile convulsive children and 0.36 +/- 0.08 pmol/ml in the nonfebrile nonconvulsive group. No statistical differences in t-MH were detected between groups. The increased susceptibility to seizures during fever may be connected to the lack of increase in CSF HA in the FC group. The data support the hypothesis that the central histaminergic neuron system may be involved in inhibition of seizures associated with febrile illnesses in childhood.

Comparative study of histamine immunoreactivity in nervous systems of Aplysia and Pleurobranchaea

The distribution of histamine in the nervous system of the marine molluscs Aplysia californica and Pleurobranchaea californica was studied by using a newly available immunohistochemical localization technique and specific antiserum against histamine-protein conjugate. We examined several sets of complete histological sections through the major ganglia of both animals, as well as all nerve roots of the buccal and cerebral ganglia and the corresponding target tissues. The results indicate that histamine is present in several neurons and/or nerve fibers of all major ganglia. An especially dense histamine fiber network in the buccal ganglion of both species suggests a major role for histamine in regulation of buccal-oral behaviors. Histamine was also observed in several identified nerve roots of the buccal and cerebral ganglia, as well as in the corresponding target tissues. Its localization in the Aplysia radular sac and in the statocyst neurons of both species suggest a role for histamine in sensory functions. Our study revealed many previously unknown histamine cells or cell clusters, some of which may be identifiable by electrophysiological methods. The findings also point to possible reinterpretation of previous findings, indicating that histamine may be a cotransmitter in identified cells, whereas the methodology itself suggests that special precautions must be taken to avoid spurious interpretations of specificity. As has now been observed in studies of serotonergic immunohistochemistry and in our own findings on VIP, histamine terminals were observed to lie in close contact with somata and axon hillocks, all of which suggest that axo-somatic connections in molluscs may be more prevalent than previously considered.

Role of brain monoamines and histamine in regulation of anterior pituitary secretion.

Role of brain monoamines and histamine in regulation of anterior pituitary secretion.