Involvement Of Histamine Receptors Research Articles

Histamine enhances keratinocyte-mediated resolution of inflammation by promoting wound healing and response to infection

The role of the epidermis in the immune response is well known. While multiple cytokines are implicated in keratinocyte-mediated infection clearance and wound healing, little is known about the involvement of keratinocytes in promoting resolution of inflammation. To assess effects of histamine stimulation on keratinocyte function. We performed a combined microarray/Gene Ontology analysis of histamine-stimulated keratinocytes. Functional changes were tested by apoptosis assessment and scratch assays. Histamine receptor involvement was also assessed by blocking wound closure with specific antagonists. Histamine treatment had extensive effects on keratinocytes, including effects on proinflammatory responses and cellular functions promoting wound healing. At the functional level, there was reduced apoptosis and enhancement of wound healing in vitro. At the receptor level, we identified involvement of all keratinocyte-expressed histamine receptors (HRHs), with HRH1 blockage resulting in the most prominent effect. Histamine activates wound healing and infection clearance-related functions of keratinocytes. While enhancement of histamine-mediated wound healing is mediated predominantly via the HRH1 receptor, other keratinocyte-expressed receptors are also involved. These effects could promote resolution of skin inflammation caused by infection or superficial injury.

Role of Histamine in Altering Fluid Recycling in Normal and Post-Traumatic Rabbit Peritoneum

This study aims to investigate if histamine induces electrochemical alterations in the normal and post-traumatic peritoneum. Peritoneal rabbit specimens were obtained before surgery and 10 days post-operatively and were mounted in Ussing chambers. Histamine solutions were added facing the intra-peritoneal and outer-peritoneal surface. Dimetindene maleate-, cetirizine-, and ranitidine-pretreated specimens were used to investigate histamine receptor involvement, whereas amiloride- and ouabain-pretreated specimens were used to investigate ion transportation blockage involvement. Trans-mesothelial resistance (R(TM)) was determined. Histamine-increased R(TM) intra-peritoneally and decreased it outer-peritoneally. A less intense effect was induced in post-traumatic specimens. Dimetindene maleate, cetirizine, amiloride, and ouabain totally inhibited this effect, whereas ranitidine only had a partial effect. Histamine induces electrochemical alterations in the normal and post-operative peritoneum. This effect is mediated by interaction with histamine receptors, hindering the normal process of ion trans-mesothelial transportation.

Initial characterization of histamine H2‐receptor overexpressing mice

Histamine is known to have positive inotropic and positive chronotropic effects in the human heart. The involvement of histamine receptors in human heart failure is controversial. However, some lines of evidence suggest that the histamine H2‐ receptor is downregulated in end‐stage heart failure and its blockade is beneficial for the patient. Therefore, we set out to generate transgenic mice which overexpress the human H2‐ receptor, labeled with a C‐terminal His tag, specifically in the heart by means of the α‐myosin heavy‐chain promoter. We obtained one line of animals where histamine was able to increase contractility in isolated left atrial preparations or isolated perfused hearts or in vivo using left ventricular echocardiography. Of importance, this effect could be blocked by cimetidine, a H2‐receptor antagonist. In contrast, histamine was inactive in preparations from littermate wild type animals. The EC50 for the inotropic and chronotropic effects in atrial preparations amounted to about 10−6M (n=6–8). The effect was accompanied by an increase in the phosphorylation state of serine 16 on phospholamban and this effect could be completely blocked by cimetidine. Immunohistochemisty revealed that the transgene using an anti His antibody was located mainly to the sarcolemma. In summary, we have generated a novel model system to study the functional role of the human histamine H2‐ receptor in a mammalian model.

On the role of histamine receptors in regulating pigmentary responses in Oreochromis mossambicus melanophores

Purpose: The present work was carried out to reveal the involvement of histamine receptors at the neuro-melanophore junction of teleost, Oreochromis mossambicus.Methods: The isolated scale melanophores were assayed using the mean melanophore size index and their responses were recorded in presence of various concentrations of histamine along with H1 and H2 receptor specific agonists and antagonist and potentiator compound 48/80.Results: Melanophores showed high sensitivity to histamine and its specific agonists. Histamine caused a dose-dependent pigment aggregation, whereas 2-(2-Pyridyl) ethylamine (PEA), a specific H1R agonist also caused aggregation in a similar manner. Conversely, amthamine, a specific H2R agonist resulted in pigment dispersion. The effects were antagonized by mepyramine; specific H1R antagonist and ranitidine a specific H2R antagonist.Conclusion: It is concluded that O. mossambicus melanophores have both H1 and H2 receptors which mediate melanophore aggregation and dispersion respectively. Compound 48/80 augmented the melanin-aggregating and dispersing effects of PEA and amthamine. It is suggested that the effect of histamine is directly mediated through H1 and H2 receptors, whereas H1Rs may be predominantly involved in the aggregatory responses.

Involvement of histamine receptors in SAPK/JNK phosphorylation

Histamine is a mediator of inflammation in allergic disease and asthma. Stress activated protein kinases/c-jun N-terminal kinases (SAPK/JNK) are involved in asthma. This study examined the role of histamine receptors on the phosphorylation of SAPK/JNK in splenocytes. C57BL/6 mice splenocytes were treated with histamine (10−4M to 10−11M), and its selective receptor agonists, phorbol 12 myristate 13-acetate (PMA) was used as a positive control, and phosphorylation of SAPK/JNK was determined. Histamine (10−4M–10−8M) inhibited phosphorylation of SAPK/JNK. H1R agonist betahistine (10−5M) decreased SAPK/JNK phosphorylation and H2R agonist amthamine (10−5M) did not show any significant effect. However, H3R agonist methimepip (10−6M) and H4R agonist 4-methyl histamine (10−6M), increased SAPK/JNK phosphorylation.We used TNFα knockout mice to determine if histamine regulated SAPK/JNK phosphorylation via TNFα. While the effects of histamine and H1 agonists were similar to that of wild type mice in inhibiting the phosphorylation of SAPK/JNK, the effects of H3 and H4 agonists differed in TNFα knockout mice splenocytes. Activation of H3 receptors decreased SAPK/JNK phosphorylation in TNFα knockout mice, as opposed to an increase in wild type mice, whereas H4 agonist did not show any significant effect on the phosphorylation of SAPK/JNK. This data showed that histamine acting through H4 receptors caused the phosphorylation of SAPK/JNK via TNFα. The role of H4 receptors in pro-inflammatory response is intriguing.

Involvement of histamine receptors in the atypical antipsychotic profile of clozapine: a reassessment in vitro and in vivo

The basis of the unique clinical profile of the antipsychotic clozapine is not yet elucidated. Brain histamine receptors may play a role in schizophrenia and its treatment, but their involvement in the profile of clozapine remained unknown. We explored the properties of clozapine and its two metabolites, N-desmethylclozapine (NDMC) and clozapine N-oxide, at the four human histaminergic receptors. We compared their active concentrations with their blood concentrations in patients treated by clozapine. We investigated the changes in receptor densities induced in rat brain by repeated administration of a therapeutic dose of clozapine. Clozapine and NDMC behaved as very potent, and partial, H(1)-receptor inverse agonists, weak, and full, H(2)-receptor inverse agonists, moderate, and protean, H(3)-receptor agonists, and moderate, and partial, H(4)-receptor agonists. Taking into account their micromolar mean blood concentrations found in 75 treated patients, and assuming that they are enriched in human brain as they are in rat brain, a full occupation of H(1)-, H(3)-, and H(4)-receptors, and a partial occupation of H(2) receptors, is expected. In agreement, repeated administration of clozapine at a therapeutic dose (20 mg/kg/day for 20 days) induced an up-regulation of H(1)- and H(2)-receptors in rat brain. Clozapine and its active metabolite NDMC interact with the four human histamine receptors at clinically relevant concentrations. This interaction may substantiate, at least in part, the atypical antipsychotic profile of clozapine, as well as its central and peripheral side effects such as sedation and weight gain.

Histamine receptors and cancer pharmacology

Considerable evidence has been collected indicating that histamine can modulate proliferation of different normal and malignant cells. High histamine biosynthesis and content together with histamine receptors have been reported in different human neoplasias including melanoma, colon and breast cancer, as well as in experimental tumours in which histamine has been postulated to behave as an important paracrine and autocrine regulator of proliferation. The discovery of the human histamine H(4) receptor in different tissues has contributed to our understanding of histamine role in numerous physiological and pathological conditions revealing novel functions for histamine and opening new perspectives in histamine pharmacology research. In the present review we aimed to briefly summarize current knowledge on histamine and histamine receptor involvement in cancer before focusing on some recent evidence supporting the novel role of histamine H(4) receptor in cancer progression representing a promising molecular target and avenue for cancer drug development.

Involvement of histamine receptors in the acquisition of inhibitory avoidance in Carassius auratus

This study investigated the involvement of H 1 and H 2 histaminegic receptors on the acquisition of a new task in Carassius auratus by using an inhibitory avoidance paradigm in which the animals had to learn to avoid an aversive stimulus. Before training, the fish received injections of H 2 antagonist zolantidine at a dose of 20 mg/kg, or H 1 antagonist chlorpheniramine at a dose of 4 or 16 mg/kg. Control animals were injected with distilled water. A facilitatory effect of chlorpheniramine was observed at the dose of 16 mg/kg. On the other hand, the administration of 20 mg/kg of zolantidine inhibited acquisition. Place preference conditioning was used to observe the aversive or reinforcing effects of the drugs, which could interfere with the inhibitory avoidance procedure; however, no effects were observed. Thus, it can be suggested that both receptors, H 1 and H 2, are involved in the acquisition of a new task in this species.

Histamine elevates the expression of Ets-1, a protooncogen in human melanoma cell lines through H2 receptor

Histamine is known to act, at least in part, as a growth factor for several cell types, and as production of this biogen amine has been found to accelerate the rate of tissue proliferation in wound repair, embryogenesis and malignant growth. Abundant experimental and clinical data suggest that histamine augments in vivo tumour cell proliferation via histamine H2 receptors (H2R). Here, we report that exogenously added histamine stimulates Ets-1 (v-ets erythroblastosis virus E26 oncogene homolog 1) synthesis in human melanoma cells. Involvement of histamine receptors in the histamine induced ets-1 expression has been also studied. Our data show that these newly recognized actions of histamine are mediated by the H2R. Modification of local protooncogen Ets-1 level is likely being involved in the regulation of melanoma growth.

Baclofen reduces emesis and gastroesophageal reflux in neurologically impaired children with gastroesophageal reflux disaese

the potential involvement of histamine receptors was also examined in current studies. Both cimetidine (1 raM) and diphenhydramine (0.1raM), H2 and H1 histamine receptor antagonists respectively, had no effect on inhibition of 36C1 uptake by TDC. In conclusion, our studies, provide direct evidence for inhibition of human intestinal luminal CI'/OH (HCO~) exchange activity by bile acids. The results of our studies demonstrate that bile acid effects on the apical CI/OH exchange in Caco2 cells are not mediated via histamine receptors and involve a cAMP-independent but Ca + +, PKC and PI3 kinase-dependent pathways.

The involvement of histamine receptors in skin depigmentation of Indian frog, rana tigrina

The involvement of histamine receptors in skin depigmentation of Indian frog, rana tigrina