Molecular Cloning and Characterization of a New Human Histamine Receptor, HH4R

Nakamura, Toshio; Itadani, Hiraku; Hidaka, Yoshiaki; Ohta, Masataka; Tanaka, K.

doi:10.1006/bbrc.2000.4008

Cited by 334 publications

(298 citation statements)

References 13 publications

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“…cAMP responding reporter construct (16,18,20,21); however, the cAMP inhibitory effect was low as compared with that of the H3R. Another study could not alter cAMP levels in H4R transfected cells, but instead increased calcium mobilization when the cells were cotransfected with G␣ q/i1/2 , G␣ q/i3 , or G ␣16 proteins (17).…”

Section: Discussionmentioning

confidence: 99%

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Histamine H4 Receptor Stimulation Suppresses IL-12p70 Production and Mediates Chemotaxis in Human Monocyte-Derived Dendritic Cells

Gutzmer

Diestel

Mommert

et al. 2005

The Journal of Immunology

222

249

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There is increasing evidence that histamine as an important mediator of immediate type allergic reactions also effects professional APCs. Recent reports showed effects of histamine on human monocyte-derived dendritic cells (MoDC) mediated primarily via histamine H1 receptors (H1R) and H2R. We show here that MoDC also express H3R and H4R at the mRNA and protein level. mRNA of the H3R is down-regulated and mRNA of the H4R is up-regulated during the differentiation from monocytes to MoDC. H4R or H2R stimulation suppressed IL-12p70 production in MoDC. Induction of cAMP was necessary for IL-12p70 inhibition mediated via the H2R. In contrast, H4R stimulation did not affect cAMP production but induced the transcription factor AP-1, and U0126, an inhibitor of AP-1 transactivation and MEK, rescued H4R mediated IL-12p70 suppression. Moreover, MoDC responded to a H4R agonist (and also to a H2R agonist) with increased F-actin polymerization and migration in modified Boyden chamber assays, suggesting a chemotactic effect of histamine via the H2R and the H4R. Thus, H4R stimulation on MoDC results in immunomodulatory and chemotactic effects. Histamine induces chemotaxis and IL-12p70 suppression via different receptors using different signaling pathways, which might be important for the pathogenesis of and therapeutic interventions in allergic diseases.

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Section: Discussionmentioning

confidence: 99%

“…Effects of the H3R and the recently cloned H4R (15)(16)(17)(18)(19)(20)(21) on cells of the adaptive immune system are less clear. H3R is primarily expressed in the CNS whereas H4R is primarily expressed on peripheral tissues such as spleen, thymus, colon, peripheral blood leukocytes, and bone marrow (15,20,22).…”

Section: Endritic Cells (Dc)mentioning

confidence: 99%

Histamine H4 Receptor Stimulation Suppresses IL-12p70 Production and Mediates Chemotaxis in Human Monocyte-Derived Dendritic Cells

Gutzmer

Diestel

Mommert

et al. 2005

The Journal of Immunology

222

249

View full text Add to dashboard Cite

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“…Similarly, by altering the lipid environment, apoE deficiency may reduce the total number of H 3 receptor binding sites available for ligand binding in the amygdala, hippocampus, and cortex. Recently, the H 4 receptor was cloned and characterized (Nakamura et al, 2000;Oda et al, 2000;Liu et al, 2001;Morse et al, 2001;Nguyen et al, 2001;Zhu et al, 2001). To determine whether H 4 signaling was involved in the observed effects on object recognition, we tested mice treated with the H 4 receptor agonist and H 3 receptor antagonist clobenpropit (Oda et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Role of H3-Receptor-Mediated Signaling in Anxiety and Cognition in Wild-Type and Apoe–/– Mice

Bongers

Leurs

Robertson

et al. 2003

Neuropsychopharmacol

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Increasing evidence supports a role for histamine as a neurotransmitter and neuromodulator in emotion and cognition. The H 3 receptor was first characterized as an autoreceptor that modulates histamine release and synthesis via negative feedback. Mice deficient in apoE (Apoe -/-) have been used to define the role of apoE in brain function. In the present study, we investigated the possible role of histamine H 3 -receptor-mediated signaling in anxiety and cognition in mice Apoe -/-and wild-type mice. H 3 antagonists increased measures of anxiety in wild-type, but not Apoe -/-, mice. In contrast, H 3 antagonists similarly impaired object recognition in wild-type and Apoe -/-mice. In Apoe -/-mice, reduced negative feedback via H 3 receptors could contribute to increased signaling of H 1 receptors. Apoe -/-mice showed higher sensitivity to the anxiety-reducing effects of the H 1 receptor antagonist mepyramine than wild-type mice. These effects were dissociated from effects of mepyramine on the HPA axis. Compared to saline controls, mepyramine reduced plasma ACTH and corticosterone levels in wild-type, but not Apoe -/-, mice. These data support a role for apoE in H 3 receptor signaling. H 3 antagonists were proposed as a treatment for cognitive disorders such as Alzheimer's disease, which is associated with increased anxiety and cognitive impairments. As H 3 antagonists increase measures of anxiety and impair object recognition in wild-type mice, the use of H 3 antagonists in cognitive disorders may be counterproductive and should be carefully evaluated.

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“…Histamine was originally considered a mediator of acute inflammatory and immediate hypersensitivity reactions but is now believed to also affect chronic inflammatory processes and to regulate the immune response. [10,11] The effects of histamine are mediated through at least four distinct cell surface, G-protein-coupled receptors (histamine H 1 , H 2 , H 3 and the newly identified H 4 ) [12][13][14][15][16][17] and eosinophils have been suggested to express all of these subtypes [10,11]. A fifth histamine receptor, located intracellularly and denoted histamine H IC , has also been described in haematopoietic cells.…”

Section: Introductionmentioning

confidence: 99%

Histamine reverses IL-5-afforded human eosinophil survival by inducing apoptosis: Pharmacological evidence for a novel mechanism of action of histamine

Hasala¹,

Giembycz²,

Janka-Junttila³

et al. 2008

Pulmonary Pharmacology & Therapeutics

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A c c e p t e d m a n u s c r i p tCaspase activities were assessed by using commercial Caspase-Glo ® 3/7, 8, and 9 luminescence assays.Histamine (10-100 µM) partially reversed IL-5-induced human eosinophil survival by enhancing apoptosis as assessed by measuring the relative DNA content of PI-stained cells.This effect was not mediated through any of the known histamine receptors or through nonspecific activation of 5-hydroxytryptamine receptors or α-adrenoceptors. Moreover, the reversal of IL-5-inhibited eosinophil apoptosis by histamine seemed not to utilize the conventional intracellular second messenger pathways including cyclic AMP, protein kinase A or phospholipase C. Inhibition of caspase 6 and caspases 1, 10 or 12 reversed the effects of histamine but also inhibited apoptosis in general.In conclusion, the data presented herein indicate that histamine induces human eosinophil apoptosis in the presence of a survival-prolonging cytokine by a mechanism that does not apparently involve the activation of any of the currently known histamine receptor subtypes.The possibility exists that another, as yet unidentified, histamine receptor may exist in human eosinophils that regulates survival, although the participation of histamine receptorindependent mechanisms cannot be excluded. 3A c c e p t e d m a n u s c r i p t

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Molecular Cloning and Characterization of a New Human Histamine Receptor, HH4R

Cited by 334 publications

References 13 publications

Histamine H4 Receptor Stimulation Suppresses IL-12p70 Production and Mediates Chemotaxis in Human Monocyte-Derived Dendritic Cells

Histamine H4 Receptor Stimulation Suppresses IL-12p70 Production and Mediates Chemotaxis in Human Monocyte-Derived Dendritic Cells

Role of H3-Receptor-Mediated Signaling in Anxiety and Cognition in Wild-Type and Apoe–/– Mice

Histamine reverses IL-5-afforded human eosinophil survival by inducing apoptosis: Pharmacological evidence for a novel mechanism of action of histamine

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