Expression Of Histamine Receptors Research Articles

Allergic Predisposition, Histamine and Histamine Receptor Expression (H1R, H2R) Are Associated with Complicated Courses of Sigmoid Diverticulitis

BackgroundWe aimed to evaluate our hypothesis that allergic predisposition and expression of histamine receptors might contribute to complicated courses of sigmoid diverticulitis. MethodsExpression of histamine and histamine receptors (H1R, H2R) was analysed on protein level (immunohistochemistry/immunofluorescence (IF)) as well as mRNA level (reverse transcription–PCR (RT-PCR) in surgical specimen of patients (n = 101) having undergone resection for sigmoid diverticulits (n = 57 complicated diverticulitis/n = 44 non-complicated diverticulitis). ResultsThe mean number of comorbid diseases per patient was 1.76 ± 1.25. Thirty-nine of 101 patients (38.6%) exhibited allergic predisposition (grass poll, food, drug, pets, etc.). Comorbid diseases were significantly associated with complicated diverticulitis (p = 0.027). Complicated sigmoid diverticulitis was significantly associated with high H1R and H2R expression (p < 0.001). Furthermore, an association of complicated diverticulitis with allergic predisposition was found (odds ratio = 3.2, p = 0.0097). IF double-labelling experiments showed a strong correlation of increased histamine expression with expression of H1R and H2R on intestinal enterocytes (histamine/H1R, rho = 0.841, p < 0.0001 and histamine/H2R, rho = 0.806, p < 0.0001). The results of increased H1R and H2R expression in complicated sigmoid diverticulitis were also detected on mRNA level in a subset of patients (RT-PCR, p = 0.009). ConclusionsOur findings suggest that allergic predisposition might be another important risk factor for complicated courses of acute sigmoid diverticulitis and linked with histamine receptor expression. Supportive therapies with antihistaminic drugs might become an option. Allergic predisposition might be worth considering when indicating surgery for sigmoid diverticulitis.

The Expression of Histamine Receptor and Chemokines in Epithelial Cells and Fibroblasts of the Upper Respiratory Tract after Respiratory Syncytial Virus (RSV) Infection

Objective: Identify the effect of RSV on upper respiratory tract infections or the symptoms of allergic rhinitis by investigating the changes of the aspect of the expressions of many chemokines or the histamine receptor when the epithelial cells of the nasal mucosa or the fibroblast are infected by RSV. Method: A mucosa sample of the inferior turbinate is obtained from 12 patients. One half of the sample is used for incubation of epithelial cells, and the other half is used in culturing fibroblasts. After infecting the cultured samples by RSV, we check the expression of Eotaxin, RANTES, IL-8, GRO-a, and HRc. Results: The study suggests that as time passes by after RSV infection, upper respiratory tract epithelial cell samples show an increase of H1RC, H2RC, H4RC, RANTES, and IL-8, and fibroblast samples show an increase of expression of H1RC, H2RC, H3RC, H4RC, GRO-a, and IL-8. Conclusion: The epithelial cells of the human upper respiratory tract, similar to those of the human lower respiratory tract, cause an influx of variable inflammatory cells and, therefore, induce inflammatory response and hyperreactivity, cause increased expression of histamine receptors, and induce symptoms similar to those of allergic rhinitis, such as rhinorrhea and sneezing.

Identification of histamine receptors and effects of histamine on murine and simian colonic excitability

Inflammatory responses can include recruitment of cells of hematopoietic origin to the tunica muscularis. These cells can secrete a variety of factors which can reset the gain of smooth muscle cells (SMC) and influence motor patterns. Histamine (H), a major mediator in inflammation, is released by mast cells and exerts diverse effects in SMC by binding to H receptors. The profiles of H receptor expression in animal models used to study inflammatory diseases are unknown. Histamine receptor expression and electro-mechanical responses to H were tested in simian and murine colonic smooth muscle using qualitative and quantitative PCR, isometric force measurements, microelectrode recordings and patch clamp techniques. H1, H2, and H4 receptor transcripts were expressed at similar levels in simian colonic tissue whereas only the H2 receptor transcript was detected in murine colonic tissue. Stimulation of simian colonic muscles with H caused depolarization and contraction in the presence of tetrodotoxin. Histamine activated non-selective cation channels in simian SMC. In contrast, H caused hyperpolarization and inhibited contractions of murine colon. The hyperpolarization was inhibited by the K(ATP) channel blocker, glibenclamide. Histamine-activated K(+) currents were inhibited by glibenclamide in murine colonic SMC. Histamine receptor expression in simian SMC was similar to that reported in humans. However, H receptor profile and responses to H were considerably different in mice. Thus, monkey colon may be a more suitable model to study how inflammatory mediators affect the gain of smooth muscle excitability.

Biogenic monoamines in preimplantation development

The involvement of biogenic monoamines in early ('preneural') embryogenesis has been well documented in lower vertebrates, but much less information is available about the role of these molecules in the earliest stages of development in mammals, including humans. Databases (PubMed, ISI Web of Knowledge and Scopus) were searched for studies relating to biogenic monoamines functioning in early embryos. The available data on the expression of histamine, serotonin and adrenergic receptors during mammalian preimplantation development were summarized, and the potential roles of biogenic monoamines in very early pregnancy were discussed. The roles of biogenic monoamines in mammalian preimplantation embryo development can be diverse, depending on the embryo developmental stage, and the physiological status of the maternal organism. Several receptors for biogenic monoamines are expressed and biologically functional in cells of preimplantation embryos. Activation of histamine receptors can play a role in embryo implantation and trophoblast invasion. Activation of adrenergic and serotonin receptors can influence proliferation and survival of early embryonic cells. Biogenic monoamines can play an important role in physiological conditions, contributing to embryo-maternal interactions, or can influence the early embryo under unfavorable or pathological conditions (e.g. in maternal stress, or in women taking certain antidepressants, anti-migraine or anti-ulcer drugs).

Histamine receptor expression, hippocampal plasticity and ammonia in histidine decarboxylase knockout mice.

Genetic ablation of the histamine producing enzyme histidine decarboxylase (HDC) leads to alteration in exploratory behaviour and hippocampus-dependent learning. We investigated how brain histamine deficiency in HDC knockout mice (HDC KO) affects hippocampal excitability, synaptic plasticity, and the expression of histamine receptors. No significant alterations in: basal synaptic transmission, long-term potentiation (LTP) in the Schaffer collateral synapses, histamine-induced transient changes in the CA1 pyramidal cell excitability, and the expression of H1 and H2 receptor mRNAs were found in hippocampal slices from HDC KO mice. However, when compared to WT mice, HDC KO mice demonstrated: 1. a stronger enhancement of LTP by histamine, 2. a stronger impairment of LTP by ammonia, 3. no long-lasting potentiation of population spikes by histamine, 4. a decreased expression of H3 receptor mRNA, and 5. less potentiation of population spikes by H3 receptor agonism. Parallel measurements in the hypothalamic tuberomamillary nucleus, the origin of neuronal histamine, demonstrated an increased expression of H3 receptors in HDC KO mice without any changes in the spontaneous firing of "histaminergic" neurons without histamine and their responses to the H3 receptor agonist (R)-α-methylhistamine. We conclude that the absence of neuronal histamine results in subtle changes in hippocampal synaptic transmission and plasticity associated with alteration in the expression of H3 receptors.

Histamine receptor H1 in the nucleus tractus solitarii regulates arterial pressure and heart rate in rats

Axons of histamine (HA)-containing neurons are known to project from the posterior hypothalamus to many areas of the brain, including the nucleus tractus solitarii (NTS), a central brain structure that plays an important role in regulating arterial pressure. However, the functional significance of NTS HA is still not fully established. In this study, we microinjected HA or 2-pyridylethylamine, a HA-receptor H(1)-specific agonist, into the NTS of urethane-anesthetized Wister rats to identify the potential functions of NTS HA on cardiovascular regulation. When HA or H(1)-receptor-specific agonist was bilaterally microinjected into the NTS, mean arterial pressure (MAP) and heart rate (HR) were significantly increased, whereas pretreatment with the H(1)-receptor-specific antagonist cetirizine into the NTS significantly inhibited the cardiovascular responses. The maximal responses of MAP and HR changes induced by HA or H(1)-receptor-specific agonist were dose dependent. We also confirmed gene expression of HA receptors in the NTS and that the expression level of H(1) mRNA was higher than that of the other subtypes. In addition, we found that H(1) receptors are mainly expressed in neurons of the NTS. These findings suggested that HA within the NTS may play a role in regulating cardiovascular homeostasis via activation of H(1) receptors expressed in the NTS neurons.

Attenuated expression of HRH4 in colorectal carcinomas: a potential influence on tumor growth and progression

BackgroundEarlier studies have reported the production of histamine in colorectal cancers (CRCs). The effect of histamine is largely determined locally by the histamine receptor expression pattern. Recent evidence suggests that the expression level of histamine receptor H4 (HRH4) is abnormal in colorectal cancer tissues. However, the role of HRH4 in CRC progression and its clinical relevance is not well understood. The aim of this study is to evaluate the clinical and molecular phenotypes of colorectal tumors with abnormal HRH4 expression.MethodsImmunoblotting, real-time PCR, immunofluorescence and immunohistochemistry assays were adopted to examine HRH4 expression in case-matched CRC samples (n = 107) and adjacent normal tissues (ANTs). To assess the functions of HRH4 in CRC cells, we established stable HRH4-transfected colorectal cells and examined cell proliferation, colony formation, cell cycle and apoptosis in these cells.ResultsThe protein levels of HRH4 were reduced in most of the human CRC samples regardless of grade or Dukes classification. mRNA levels of HRH4 were also reduced in both early-stage and advanced CRC samples. In vitro studies showed that HRH4 over-expression caused growth arrest and induced expression of cell cycle proteins in CRC cells upon exposure to histamine through a cAMP -dependent pathway. Furthermore, HRH4 stimulation promoted the 5-Fu-induced cell apoptosis in HRH4-positive colorectal cells.ConclusionThe results from the current study supported previous findings of HRH4 abnormalities in CRCs. Expression levels of HRH4 could influence the histamine-mediated growth regulation in CRC cells. These findings suggested a potential role of abnormal HRH4 expression in the progression of CRCs and provided some new clues for the application of HRH4-specific agonist or antagonist in the molecular therapy of CRCs.

Histamine H4 receptors in normal conjunctiva and in vernal keratoconjunctivitis

While it is known that histamine is the primary mediator of ocular allergy, the presence and distribution of histamine receptors are not well documented in the human eye. Our aim was to evaluate histamine receptor expression in normal and vernal keratoconjunctivitis conjunctiva. Mucosal biopsies were obtained from conjunctiva of healthy donors and from tarsal conjunctiva of vernal patients. Immunostaining and semi-quantitative reverse-transcriptase polymerase chain reaction for H(1), H(2), H(3), and H(4) receptors were performed. Histamine receptor expression was also evaluated in conjunctival cell cultures exposed to histamine, interleukin-4, interleukin-5, interferon-γ and tumor necrosis factor-α. Immunostaining for H(1) and H(2) receptors was slightly positive in normal and over-expressed in vernal tissues. H(3) receptors were rarely present in normal and inflamed conjunctiva. In striking contrast to control tissues, H(4) receptors were highly expressed in all inflamed tissues, particularly by stromal inflammatory cells. Semi-quantitative reverse-transcriptase polymerase chain reaction demonstrated an over-expression of H(1), H(2), and H(4) receptors in vernal vs control tissues. Notably, H(4) receptors were five times more expressed in vernal vs control tissues. In cell cultures, H(2) receptor expression was stimulated eight times the normal levels by interleukin-4 and three times by histamine, but the H(4) receptor was only slightly affected by stimulation with these mediators. Increased expression of H1, and particularly of H(2) and H(4) receptors in vernal keratoconjunctival tissues indicate their important role in the pathogenesis of this disease. H(4) receptors may be a target in the treatment of allergic inflammation.

Allergic Predisposition, Histamine and Histamine Receptor Expression (H1R, H2R) Are Associated With Complicated Courses of Sigmoid Diverticulitis

Allergic Predisposition, Histamine and Histamine Receptor Expression (H1R, H2R) Are Associated With Complicated Courses of Sigmoid Diverticulitis

Insights into the physiomodulatory role of histaminergic receptors in vertebrate skin pigmentation

All organisms, from simple invertebrates to complex human beings, exist in different colors and patterns, which arise from unique distribution of pigments throughout the body. Being the largest organ of the body, skin is always under the influence of internal and external factors that often react to certain intrinsic agents in an unorthodox manner, modifying the integral pigmentation patterns and resulting into complex physiological aberrancies. One of these intrinsic agents involved in numerous immunological and non-immunological processes within the body is histamine. Histamine mediates its multifarious biological activities stimulated by various immunological and non-immunological stimuli via differential expression of its four classes of receptors (H1, H2, H3, and H4) on effector cells. Interestingly, recent studies have described the expression of functional histamine receptors in vertebrate pigment cells melanocytes, emphasizing the potential physiomodulatory effects of this molecule in the phenomenon of skin pigmentation. This noteworthy finding has opened numerous perspectives to elucidate several contentions regarding skin-related conditions. The focus of this review is to provide an updated overview of the involvement and role of histamine and its receptors together with the physiological and pharmacological aspects of their agonists and antagonists impinging the phenomenon of pigmentation and the mechanisms by which they do so.

Histamine induces Th2 activation through the histamine receptor 1 in house dust mite rhinitic but not asthmatic patients

Effects of mast cell-released histamine on smooth muscle and endothelial cells are considered as responsible of immediate symptoms of anaphylaxis. However, little is known about histamine effects on Th2 lymphocytes, which orchestrate the allergic reaction upstream of mast cells. We addressed this question in house dust mite (HDM) allergics, according to the presence of rhinitis or asthma and allergen stimulation. Peripheral blood mononuclear cell from 15 rhinitic and 14 asthmatic HDM-allergic subjects and 16 controls were cultured with Der p 1 or histamine. The effect of Der p 1 on histamine receptor (H1R and H2R) expression was studied. T-cell cytokine production was studied upon Der p 1 or histamine stimulation. The role of H1R in histamine effects was assessed with levocetirizine. H1R and H2R are overexpressed on T cells from asthmatic but not from rhinitic subjects. Der p 1 increases H1R expression on CD4(+) cells from both allergic groups, and decreases it in controls, on CD4(+) and CD8(+) subsets. Der p 1 decreases T-cell H2R expression in asthmatics. Allergen increases IL-4 and IL-13 in both allergic groups. Histamine increases Th2 cytokines in rhinitics only, and levocetirizine abolishes this effect. In asthmatics and controls, histamine decreases T-cell cytokines through a non-H1R dependent pathway. In rhinitis but not in asthma, histamine is able to increase allergic inflammation by increasing Th2 cytokine production in a positive feedback dependent on H1R. This result could explain in part why H1R antagonists, are very efficient in rhinitis, but not in asthma.

Histamine Stimulates Interleukin-6 Production through Histamine H1 Receptors in Human Amnion Cells

Background/Aims: Previous studies have stated that maternal allergic diseases are associated with increased risk of preterm labor/delivery, but the underlying mechanisms remain unclear. This study tested the hypothesis that histamine induces interleukin (IL)-6 production in amnion cells. Methods: Using cultured human amnion cells, we examined expression of histamine receptors and effects of histamine on IL-6 production. Results: Reverse transcription-polymerase chain reaction and Western blotting revealed expression of histamine H1 receptor (H1R) and H2 receptor (H2R) in human amnion. Histamine stimulation significantly increased concentrations of IL-6 in conditioned medium, as did tumor necrosis factor-α and IL-1β in positive controls. In addition, the H1R antagonist olopatadine significantly blocked histamine-induced production of IL-6, whereas the H2R antagonist ranitidine did not. Conclusion: Histamine appears to induce IL-6 production through H1R in human amnion cells.

Differences in the expression of histamine-related genes and proteins in normal human adrenal cortex and adrenocortical tumors

Histamine is involved in the pathogenesis of several tumors; however, there are no data on its possible involvement in human adrenocortical tumorigenesis. The expression of genes and proteins involved in the biosynthesis (histidine decarboxylase, HDC), action (histamine receptors: HRH1-HRH4), and metabolism of histamine is largely unknown both in the normal human adrenal cortex and in adrenocortical tumors. In this study, we examined the expression of histamine-related genes and proteins and histamine content in normal adrenal cortex, benign adrenocortical adenomas, and malignant adrenocortical cancer (ACC). Fifteen normal adrenals and 43 tumors were studied. mRNA expression was examined by real time RT-PCR. Western-blotting and immunohistochemistry were used for the study of proteins. Tissue histamine content was determined by enzyme-linked immunosorbent assay. We found that all proteins involved in histamine biosynthesis and action are present both in the normal adrenal cortex and in the tumors studied. HDC expression and histamine content was highest in the normal tissues and lower in benign tumors, whereas it was significantly less in ACCs. HRH3 expression was significantly higher in ACC samples than in the other groups. Adrenocortical tumorigenesis might, thus, be characterized by reduced histamine biosynthesis; furthermore, different adrenocortical tumor subtypes may show unique histamine receptor expression profiles.

Calyx and dimorphic neurons of mouse Scarpa's ganglion express histamine H3 receptors

BackgroundHistamine-related drugs are commonly used in the treatment of vertigo and related vestibular disorders. The site of action of these drugs however has not been elucidated yet. Recent works on amphibians showed that histamine H3 receptor antagonists, e.g. betahistine, inhibit the afferent discharge recorded from the vestibular nerve. To assess the expression of H3 histamine receptors in vestibular neurons, we performed mRNA RT-PCR and immunofluorescence experiments in mouse Scarpa's ganglia.ResultsRT-PCR analysis showed the presence of H3 receptor mRNA in mouse ganglia tissue. H3 protein expression was found in vestibular neurons characterized by large and roundish soma, which labeled for calretinin and calbindin.ConclusionThe present results are consistent with calyx and dimorphic, but not bouton, afferent vestibular neurons expressing H3 receptors. This study provides a molecular substrate for the effects of histamine-related antivertigo drugs acting on (or binding to) H3 receptors, and suggest a potential target for the treatment of vestibular disorders of peripheral origin.

Histamine Promotes Osteoclastogenesis through the Differential Expression of Histamine Receptors on Osteoclasts and Osteoblasts

In addition to the numerous roles of histamine in both the immune and nervous systems, previous studies have suggested that this bioamine might also be involved in bone metabolism. Following our observations of impaired bone resorption in ovariectomized rats after histamine receptor antagonist treatment, we focused in this study on osteoclasts and osteoclast precursors. We looked for a direct action of histamine on these cells using both in vivo and in vitro approaches. In vivo, we triggered a remodeling sequence in rat mandibular bone and treated the animals with either histamine or histamine receptor antagonists. Histamine was shown to increase the number of osteoclasts and osteoclast precursors whereas antagonists of histamine receptor-1 and -2 decreased both osteoclast recruitment and resorption. In vitro, spleen cells from histamine-deficient mice were treated with receptor activator for nuclear factor kappa B ligand and macrophage colony stimulating factor, giving rise to both reduced numbers of osteoclasts and decreased resorption on dentin slices. Histamine enhanced resorption in these cultures in a dose-dependent manner. In addition, we identified osteoclast precursors as a source of histamine. In contrast, histamine increased the receptor activator for nuclear factor kappa B ligand/osteoprotegerin ratio in primary osteoblasts that did not secrete histamine. We observed a differential expression of histamine receptor-1 and -2 mRNAs in both primary osteoclasts and osteoblasts, confirming their functional roles with selective antagonists. Thus, histamine acts directly on osteoclasts, osteoclast precursors, and osteoblasts, promoting osteoclastogenesis through autocrine/paracrine mechanisms.

Histamine H4 receptors modulate dendritic cell migration through skin – immunomodulatory role of histamine

Dendritic cells (DC) are the major antigen-presenting cells and play a key role in adaptive immunity as they are able to activate naive T cells. It was recently described, that the histamine H(4) receptor (H4R) is present on human monocyte-derived DC and that chemotaxis and T-helper (Th)1-Th2 polarization is mediated by this receptor. However, the distribution of histamine receptors on murine DC has not been studied yet. The histamine receptor expression on murine bone marrow (BM)-derived DC and effects of histamine and H4R agonism on DC migration through skin were studied. As it was demonstrated in scratching experiments that NMRI mice are more susceptible to H4R-mediated itch than BALB/c mice, DC function of NMRI and BALB/c mice was compared. The mRNA of the H1R, H2R and H4R could be detected in murine BM-derived DC, while mRNA of the H3R was found to be low or undetectable. There were no distinct differences in mRNA expression and in H4R protein level (flow cytometry) between NMRI compared with BALB/c mice indicating, that a higher susceptibility is not associated with a generally higher H4R expression in all cell types. Histamine as well as the H4R agonist clobenpropit induced an enhanced chemotaxis in the skin DC migration assay. The enhanced chemotaxis was blocked by the H4R antagonist JNJ7777120. This finding was confirmed by in vitro migration experiments with BM-derived DC. Referring to DC migration, blocking the H4R on inflammatory cells might be a promising anti-inflammatory, immunomodulatory strategy.

Genetic variability of histamine receptors in patients with Parkinson's disease

BackgroundChanges in the density and expression of histamine receptors (HRH) have been detected in Parkinson's disease (PD) patients, and HRH antagonists bring about improvements in motor and other symptoms, thus suggesting that HRH play a role in the clinical response of PD patients. This study is aimed to analyse polymorphic variations of HRH in patients with PD.MethodsLeukocytary DNA from 195 PD patients and a control group of 231 unrelated healthy individuals was studied for the nonsynonymous HRH1Leu449Ser and the promoter HRH2G-1018A polymorphisms by using amplification-restriction analyses.ResultsThe HRH1Leu449Ser amino acid substitution was identified in two women with late-onset PD whereas it was not observed among healthy subjects. The HRH2G-1018A polymorphism was observed with allele frequencies = 3.59 (95% CI = 1.74–5.44) and 5.0 (95% CI = 3.00–6.96) for patients with PD and healthy controls, respectively. These frequencies were independent of gender and age of onset of the disease. Multiple comparison analyses revealed that differences were not statistically significant.ConclusionThese results indicate that the polymorphisms analyzed are not a major risk factor for PD, although the HRH1Leu449Ser amino acid substitution might be related to PD.

Histamine H1 receptors are expressed in mouse and frog semicircular canal sensory epithelia

Histamine-related drugs are commonly used in the treatment of vertigo and related vestibular disorders. Their site and mechanism of action, however, are still poorly understood. To increase our knowledge of the histaminergic system in the vestibular organs, we have investigated the expression of H1 and H3 histamine receptors in the frog and mouse semicircular canal sensory epithelia. Analysis was performed by mRNA reverse transcriptase-PCR, immunoblotting and immunocytochemistry experiments. Our data show that both frog and mouse vestibular epithelia express H1 receptors. Conversely no clear evidence for H3 receptors expression was found.

Decreased expression of histamine H1 and H4 receptors suggests disturbance of local regulation in human colorectal tumours by histamine

Production of histamine in colon tumours has been described earlier. Histamine-mediated signals have been shown to be implicated in tumour growth, and the effects of histamine are largely determined locally by the histamine receptor expression pattern. We analysed histamine receptor expression in human colorectal cancer, adenoma and normal mucosa by quantitative reverse transcription-polymerase chain reaction (RT-PCR), Western blot analysis and immunostaining. Real-time RT-PCR results revealed significantly decreased ( p<0.001) H1R and H4R mRNA levels in tumours compared to normal colonic mucosa, without any significant change in H2R mRNA expression. H3R was absent in most samples; it was detected at low levels in 7.9% of the cases. Protein analysis showed a similar decrease in histamine receptor expression in carcinoma and adenoma compared to normal mucosa controls. Based on these results, we performed further Western blot analysis on Dukes-classified and -selected tumour samples. We found significantly decreased H4R levels in neoplastic samples compared to normal colonic tissue, but there was no significant correlation between histamine receptor expression profile and the Dukes stage of tumours. Immunohistochemical staining revealed expression patterns of H1R, H2R and H4R similar to those suggested by the mRNA and Western blot results. In the present study, we demonstrate that H1R, H2R and H4R are expressed in colon carcinoma and the adjacent normal mucosa. The results suggest a dramatic alteration in the distribution of histamine receptors in colon cancer. These findings raise the perspective of targeted pharmacological studies with selective histamine receptor antagonists or agonists in the therapy of colorectal tumours.

Expression of histamine receptors (H 1, H 2, and H 3) in the rabbit endolymphatic sac: an immunohistochemical study

Objective The endolymphatic sac (ES) is part of the membranous labyrinth of the inner ear. Its central role in immunologic activity within the inner ear has been confirmed by numerous studies. The aim of this study was to investigate the expression of histamine receptors (H 1, H 2, H 3) in the rabbit ES. Methods A total of 10 healthy male New Zealand white rabbits weighing 2 to 3 kg were used in the experiments. For immunohistochemical studies, immunostaining was performed according to the avidin-biotin-peroxidase complex technique. Results Serial sections of the ES of rabbits revealed the presence of H 1, H 2, and H 3 receptor immunoreactivity. Immunoreactive cells for all H 1, H 2, and H 3 were found in the epithelial and subepithelial layers of the duct and the proximal ES. In conclusion, this study showed the immunohistochemical localization of H 1, H 2, and H 3 receptors in the ES of rabbits. These receptors may be important in the homeostasis of the inner ear. In addition, they may be target receptors in the medical treatment of inner ear disorders such as endolymphatic hydrops.