Histamine H1-receptors in HL-60 monocytes are coupled to Gi-proteins and pertussis toxin-insensitive G-proteins and mediate activation of Ca2+ influx without concomitant Ca2+ mobilization from intracellular stores

Seifert, Roland; Grünbaum, Lore; Schultz, Günter

doi:10.1007/bf00170880

Cited by 17 publications

(19 citation statements)

References 43 publications

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“…Our results provide evidence that, besides the well known activation of Gaq, the H 1 R can also couple efficiently to Gai 1 proteins, in agreement with previously published results (Murayama et al, 1990;Seifert et al, 1994). We also found a small increase in cAMP production following H 1 R activation, which provides evidence toward Gas coupling via H 1 R. Activation of the H 2 R greatly increased the production of cAMP, which was described previously, but surprisingly we also found a Gaq-mediated increase in Ca 21 upon stimulation of this receptor.…”

Section: Discussionsupporting

confidence: 93%

Quantitative Single-Cell Analysis of Signaling Pathways Activated Immediately Downstream of Histamine Receptor Subtypes

Unen

Rashidfarrokhi

Hoogendoorn

et al. 2016

Molecular Pharmacology

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Genetically encoded biosensors based on Förster resonance energy transfer (FRET) can visualize responses of individual cells in real time. Here, we evaluated whether FRET-based biosensors provide sufficient contrast and specificity to measure activity of G-protein-coupled receptors. The four histamine receptor subtypes (H 1 R, H 2 R, H 3 R, and H 4 R) respond to the ligand histamine by activating three canonical heterotrimeric G-protein-mediated signaling pathways with a reported high degree of specificity. Using FRET-based biosensors, we demonstrate that H 1 R activates Gaq. We also observed that H 1 R activates Gai, albeit at a 10-fold lower potency. In addition to increasing cAMP levels, most likely via Gas, we found that the H 2 R induces Gaq-mediated calcium release. The H 3 R and H 4 R activated Gai with high specificity and a high potency. We demonstrate that a number of FRET sensors provide sufficient contrast to: 1) analyze the specificity of the histamine receptor subtypes for different heterotrimeric G-protein families with single-cell resolution, 2) probe for antagonist specificity, and 3) allow the measurement of single-cell concentration-response curves.

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Section: Discussionsupporting

confidence: 93%

Quantitative Single-Cell Analysis of Signaling Pathways Activated Immediately Downstream of Histamine Receptor Subtypes

Unen

Rashidfarrokhi

Hoogendoorn

et al. 2016

Molecular Pharmacology

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“…Similar results regarding the HA effect on U937 promonocytes were obtained with monocytoid-differentiated HL-60 cells (Seifert et al, 1994), the only difference being that the dual HA H 3 receptor/H 4 R antagonist thioperamide ) was used instead of JNJ. The latter ligand did not ] i after stimulation with (A and B) HA (10 mM) and (C and D) UR-PI376 (10 mM) in the presence or absence of JNJ (1 mM).…”

Section: Resultssupporting

confidence: 69%

“…4 and 5). As was the case for monocytoiddifferentiated HL-60 cells (Seifert et al, 1994), the HA-induced increases in [Ca 21 ] i in U937 promonocytes were mediated by cation channels (Supplemental Fig. 6).…”

Section: No Evidence For H 4 R In Human Monocytesmentioning

confidence: 52%

“…examined HA-induced increases in [Ca 21 ] i in U937 cells. The the data were not published because they simply confirmed the data obtained with monocytoid-differentiated HL-60 cells (Seifert et al, 1994). However, in the context of our current discussion on the assumed expression of H 4 R in monocytes, those previous data have become again relevant.…”

Section: No Evidence For H 4 R In Human Monocytesmentioning

confidence: 64%

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No Evidence for Histamine H4 Receptor in Human Monocytes

Werner

Neumann

Buschauer

et al. 2014

The Journal of Pharmacology and Experimental Therapeutics

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The histamine H 4 receptor (H 4 R) is a classic pertussis toxinsensitive G i protein-coupled receptor that mediates increases in intracellular calcium concentration ([Ca 21 ] i ). The presence of H 4 R in human eosinophils has been rigorously documented by several independent groups. It has also been suggested that H 4 R is expressed in human monocytes, but this suggestion hinges in part on H 4 R antibodies with questionable specificity. This situation prompted us to reinvestigate H 4 R expression in human monocytes. As positive control, we studied human embryonic kidney 293T cells stably expressing the human H 4 R (hH 4 R). In these cells, histamine (HA) and the H 4 R agonistHowever, in quantitative real-time polymerase chain reaction studies we failed to detect hH 4 R mRNA in human monocytes and U937 promonocytes. In human monocytes, ATP and] i , but HA, UR-PI376, and 5-methylhistamine (a dual H 4 R/H 2 receptor agonist) did not. In U937 promonocytes and differentiated U937 cells, HA increased [Ca 21 ] i , but this increase was mediated via HA H 1 receptor. In conclusion, there is no evidence for the presence of H 4 R in human monocytes.

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“…calcium levels in most systems, as well as the activation of small G proteins Rac and RhoA (Gutowski et al, 1991;Notcovich et al, 2010). Alternatively, in native and heterologous H 1 R expression systems, H 1 R signaling via Gi/o, phospholipase A2 activation, and cGMP and nitric oxide production has been described (Richelson, 1978;Snider et al, 1984;Leurs et al, 1994;Seifert et al, 1994;Wang and Kotlikoff, 2000;Prast and Philippu, 2001). In the mammalian brain, adrenal glands, and Chinese hamster ovary cells, activation of H 1 R may also stimulate adenylyl cyclase (AC) with consequent intracellular cAMP production (Keogh and Marley, 1991;Marley et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

Current Knowledge and Perspectives on Histamine H1 and H2 Receptor Pharmacology: Functional Selectivity, Receptor Crosstalk, and Repositioning of Classic Histaminergic Ligands

Monczor

Fernández

2016

Molecular Pharmacology

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H 1 and H 2 histamine receptor antagonists, although developed many decades ago, are still effective for the treatment of allergic and gastric acid-related conditions. This article focuses on novel aspects of the pharmacology and molecular mechanisms of histamine receptors that should be contemplated for optimizing current therapies, repositioning histaminergic ligands for new therapeutic uses, or even including agonists of the histaminergic system in the treatment of different pathologies such as leukemia or neurodegenerative disorders. In recent years, new signaling phenomena related to H 1 and H 2 receptors have been described that make them suitable for novel therapeutic approaches. Crosstalk between histamine receptors and other membrane or nuclear receptors can be envisaged as a way to modulate other signaling pathways and to potentiate the efficacy of drugs acting on different receptors. Likewise, biased signaling at histamine receptors seems to be a pharmacological feature that can be exploited to investigate nontraditional therapeutic uses for H 1 and H 2 biased agonists in malignancies such as acute myeloid leukemia and to avoid undesired side effects when used in standard treatments. It is hoped that the molecular mechanisms discussed in this review contribute to a better understanding of the different aspects involved in histamine receptor pharmacology, which in turn will contribute to increased drug efficacy, avoidance of adverse effects, or repositioning of histaminergic ligands.

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Histamine H1-receptors in HL-60 monocytes are coupled to Gi-proteins and pertussis toxin-insensitive G-proteins and mediate activation of Ca2+ influx without concomitant Ca2+ mobilization from intracellular stores

Cited by 17 publications

References 43 publications

Quantitative Single-Cell Analysis of Signaling Pathways Activated Immediately Downstream of Histamine Receptor Subtypes

Quantitative Single-Cell Analysis of Signaling Pathways Activated Immediately Downstream of Histamine Receptor Subtypes

No Evidence for Histamine H4 Receptor in Human Monocytes

Current Knowledge and Perspectives on Histamine H1 and H2 Receptor Pharmacology: Functional Selectivity, Receptor Crosstalk, and Repositioning of Classic Histaminergic Ligands

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