Expression of histamine receptors in different cell lines derived from mammary gland and human breast carcinomas

Inflammation Research -     

Selective cognitive dysfunction in mice lacking histamine H1 and H2 receptors

Previous pharmacological experiments provide conflicting findings that describe both facilitatory and inhibitory effects of neuronal histamine on learning and memory. Here, we examined learning and memory and synaptic plasticity in mice with a null mutation of gene coding histamine H1 or H2 receptor in order to clarify the role of these receptors in learning and memory processes. Learning and memory were evaluated by several behavioral tasks including object recognition, Barnes maze and fear conditioning. These behavioral tasks are highly dependent on the function of prefrontal cortex, hippocampus or amygdala. Object recognition and Barnes maze performance were significantly impaired in both H1 receptor gene knockout (H1KO) and H2 receptor gene knockout (H2KO) mice when compared to the respective wild-type (WT) mice. Conversely, both H1KO and H2KO mice showed better auditory and contextual freezing acquisition than their respective WT mice. Furthermore, we also examined long-term potentiation (LTP) in the CA1 area of hippocampus in H1KO and H2KO mice and their respective WT mice. LTP in the CA1 area of hippocampus was significantly reduced in both H1KO and H2KO mice when compared with their respective WT mice. In conclusion, our results demonstrate that both H1 and H2 receptors are involved in learning and memory processes for which the frontal cortex, amygdala and hippocampus interact.     

Histamine receptors in human mammary gland,different benign lesions and mammary carcinomas

Inflammation Research -     

Participation of H1 and H2 histamine receptors in physiological vasodilator responses.

Histamine causes vasodilation in the dog by activation of H1 and H2 receptors blocked by mepyramine and metiamide, respectively. Experiments were conducted in anesthetized dogs to determine the participation of H1 and H2 receptors in several forms of physiological dilatation. Mepyramine attenuated both histamine-induced and active-reflex dilatation in the hindlimb. Metiamide caused a further reduction in both sets of dilatation. Neither single nor combined antihistamines reduced dilatation due to exercise or after temporary occlusion of the circulation in the hindlimb. Poststimulation dilatation in the gracilis muscle was partially attenuated by metiamide or mepyramine. Neither dilatation caused by sympathetic nerve stimulation in the hindpaw nor dilatation in the gracilis muscle caused by compound 48/80 was reduced by mepyramine. Following combined H1- and H2-receptor blockade, portions of both types of dilatation were reduced. These data provide evidence for the participation of both types of histamine receptor in active reflex dilatation, low-frequency neurogenic dilatation, dilatation caused by compound 48/80, and poststimulation dilatation. Neither type of histamine receptor appears to be involved in reactive hyperemia or dilatation caused by exercise.     

H1 and H2 histamine receptors in histiocytic lymphoma cell line U-937

Inflammation Research -     

Functional heterogeneity of histamine H1 receptors

Inflammation Research -     

Characterization and autoradiographic localization of histamine H1 receptors in human nasal turbinates.

To examine the localization of histamine H1 receptors (H1R) in human nasal mucosa, the autoradiographic distribution of H1R was studied in human nasal inferior turbinates. Cryostat sections were incubated with various concentration of [3H]pyrilamine in saturation-binding studies and with 1 nmol/L of [3H]pyrilamine for autoradiography. Nonspecific binding was determined by adding 2 mumol/L of pyrilamine. Scatchard analysis demonstrated high-affinity binding sites with a maximum binding capacity of H1R of 193 +/- 46 fmol/mg of protein, and dissociation constant was 0.6 +/- 0.1 nmol/L. Autoradiograms indicated H1R exist exclusively on the endothelium of vessels. No specific labeling could be observed in the submucosal glands or epithelium. These results extend and support our previous finding that histamine directly causes vascular permeability through H1R and stimulates nasal glandular secretion indirectly through reflexes.     

Ligand-directed multifunctional signaling of histamine H1 receptors

Inflammation Research - .     

Involvement of histamine and histamine H2 receptors in nicotinamide-induced differentiation of human amniotic epithelial cells into insulin-producing cells

Objective and design

Human amniotic epithelial cells (HAEC) resemble stem cells in their ability to differentiate into all three germ layers: endoderm, mesoderm, and ectoderm. Histamine receptors are expressed on HAEC. We examined the influence of histamine, and H₁ and H₂ antagonists on the generation of pancreatic islet beta-like cells from HAEC.

Materials and methods

HAEC were isolated after term pregnancies (N = 12) and cultured for 14 days with nicotinamide (10 mM) in normoxia. Altogether, 72 cultures were established. Histamine (100 μM) effects were investigated with mepyramine (10 μM) or cimetidine (10 μM). After 7 and 14 days, the mean concentration of C-peptide (MCCP) in the culture medium was measured immunoenzymatically as a marker of pancreatic differentiation.

Results

MCCP was approximately threefold higher on day 14, compared to day 7. Histamine significantly increased MCCP, and more evident differences were observed after 7 days of culture than after 14 days. The mean percent increase ±SEM in MCCP amounted to 142.19 ± 21.7 and 79.03 ± 12.35 compared to the controls on day 7 and 14, respectively. H₂ blockade significantly reduced histamine-related increase in MCCP, both on day 7 and 14 by 88.7 ± 14.3 and 39.2 ± 12.4%, respectively. H₁ receptor antagonist did not affect MCPP.

Conclusion

Nicotinamide-induced pancreatic differentiation of HAEC into beta-like cells may be augmented, probably at its earlier stage, by histamine acting via H₂ receptors.

     

Phosphorylation of human histamine H1 receptors and its role in agonist-induced receptor internalization and down-regulation

Inflammation Research -     

Opposite functions of histamine H1 and H2 receptors and H3 receptor in substantia nigra pars reticulata

The substantia nigra pars reticulata (SNr) is a key basal ganglia output nucleus. Inhibitory outputs from SNr are encoded in spike frequency and pattern of the inhibitory SNr projection neurons. SNr output intensity and pattern are often abnormal in movement disorders of basal ganglia origin. In Parkinson's disease, histamine innervation and histamine H3 receptor expression in SNr may be increased. However, the functional consequences of these alterations are not known. In this study, whole cell patch-clamp recordings were used to elucidate the function of different histamine receptors in SNr. Histamine increased SNr inhibitory projection neuron firing frequency and thus inhibitory output. This effect was mediated by activation of histamine H1 and H2 receptors that induced inward currents and depolarization. In contrast, histamine H3 receptor activation hyperpolarized and inhibited SNr inhibitory projection neurons, thus decreasing the intensity of basal ganglia output. By the hyperpolarization, H3 receptor activation also increased the irregularity of the interspike intervals or changed the pattern of SNr inhibitory neuron firing. H3 receptor-mediated effects were normally dominated by those mediated by H1 and H2 receptors. Furthermore, endogenously released histamine provided a tonic, H1 and H2 receptor-mediated excitation that helped keep SNr inhibitory projection neurons sufficiently depolarized and spiking regularly. These results suggest that H1 and H2 receptors and H3 receptor exert opposite effects on SNr inhibitory projection neurons. Functional balance of these different histamine receptors may contribute to the proper intensity and pattern of basal ganglia output and, as a consequence, exert important effects on motor control.     

Some studies of the action of betahistine at H1 and H2 receptors for histamine

Betahistine produced a concentration-dependent contraction of the guinea-pig ileum and was about 27 times less active than histamine in this respect. Betahistine induced desensitization of contractile responses to histamine in the guinea-pig ileum. The H1 histamine receptor antagonist mepyramine was a competitive antagonist of the action of betahistine on the guinea-pig ileum.Betahistine caused relaxation of the rat uterus contracted by acetylcholine, and this action of betahistine was blocked by the H2 receptor antagonist cimetidine. Betahistine had a concentration-dependent positive chronotropic action on isolated guinea-pig atria, and in this respect was tenfold less potent than histamine. The action of betahistine on the atria was blocked by the H2 receptor antagonist YM11170. Betahistine caused a concentration-related contraction of the isolated lung parenchymal strip of the guinea-pig, and YM11170 potentiated this effect.Betahistine failed to release histamine from rat peritoneal mast cells at concentrations up to 100 M and it did not prevent histamine release induced by either substance P or anti-IgE.Betahistine produced a dose-related flare and wheal reaction when injected intradermally into human skin.It is concluded that betahistine has agonist activity at both H1 and H2 receptors for histamine.     

Localisation of mRNAs for diamine oxidase and histamine receptors H1 and H2, at the feto-maternal interface of human pregnancy

OBJECTIVE AND DESIGN: To localise mRNAs for the histamine receptors H1, H2 and H3, and for diamine oxidase, in the placenta and decidua of the human feto-maternal interface. MATERIALS AND METHODS: Complementary DNA for each mRNA of interest was amplified by polymerase chain reaction. Sub-cloned sequences were used to prepare probes for in situ hybridisation, and these were employed to localise the expression of mRNAs for histamine receptors H1 and H2, and for diamine oxidase. RESULTS: mRNA for histamine receptors H1 and H2, and for diamine oxidase could be detected at the feto-maternal interface of human pregnancy, and localised to both decidual and placental cells. CONCLUSION: The co-expression of these receptors and DAO is consistent with a role for histamine at the feto-maternal interface of human pregnancy.     

Mouse mammary epithelial cells bear histamine receptors

Inflammation Research -     

The participation of H1 and H2 histamine receptors in vascular skin permeability induced by some imidazoles

Conclusions The inhibitory action of both types of histamine receptor antagonists on imidazole-induced skin vascular permeability suggests that histamine receptors are involved in this phenomenon.The mechanism of the action of imidazoles on skin vessels may be related to the endogenously released histamine [7] which subsequently stimulates its receptors and/or directs stimulation by imidazoles of both types of histamine receptors present in the vascular tree.     

Histamine regulates lymphocyte mitogenic responses through activation of specific H1 and H2 histamine receptors.

In previous studies we have reported that patients with mild atopic eczema have enhanced lymphocyte mitogenesis while those with severe disease have markedly suppressed responses. Similarly, histamine in low concentrations enhanced mitogenesis while higher levels inhibit mitogen stimulated thymidine uptake. In the present study, we investigated the kinetics of this response and the interaction of histamine with its cell-surface receptors on lymphocytes. Histamine (10(-3) M) markedly inhibited [3H]-thymidine incorporation to 27% of control levels when added at the beginning of a 72 h culture period. When added after 24 and 48 h of culture, however, the suppression was much less (62 and 88% of control). Lymphocyte cultures pulsed for 1 h with histamine, washed free of the agent and then cultured with mitogen also showed marked suppression of [3H]-thymidine uptake. The kinetics of the response suggest that histamine acts to inhibit initial processing or recruitment steps in the mitogenic assay. Cimetidine, an H2-receptor blocking agent, prevented the suppressive effect of high levels of histamine while diphenhydramine, an H1 blocker, abolished the enhancement observed with low levels. Pre-incubation of mononuclear cell suspensions, which has been shown to decrease suppressor activity, resulted in a decreased response to added histamine. This change in histamine responsiveness was associated with an alteration in H1:H2 histamine binding as determined with a radiolabelled ligand-binding assay. Histamine suppression of mitogenesis was associated with an increase in cellular cAMP levels while enhancement was accompanied by a small increase in cGMP. These data suggest that lymphocyte function may be regulated, in part, by histamine receptor bearing cells with H1 stimulation having a role in enhancement of mitogenesis and H2 stimulation resulting in normal suppressor activity.