Genomic organization and characterization of splice variants of the human histamine H3 receptor

Cogé, Francis; Guenin, Sophie-Pénélope; Audinot, Valérie; Renouard-Try, Anne; Beauverger, Philippe; Macia, Christelle; Ouvry, Christine; Nagel, Nadine; Rique, Hervé; Boutin, Jean A.; Galizzi, Jean‐Pierre

doi:10.1042/0264-6021:3550279

Cited by 92 publications

(50 citation statements)

References 19 publications

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“…This is also similar to the published K d values for histamine [47,48]. The results demonstrate, therefore, that this is a very fast association [46,49,50] and that both histamine and imetit showed the expected behaviour, in that they were able to increase the nFRET signal in a time-and concentration-dependent manner. Analysis of kinetics of receptors induced by different agonists in living cells showed that receptor modulation occurs very rapidly, and different agonists act differently on different receptor subtypes [51].…”

Section: Agonist-induced Activation Of Intramolecular H3 Receptor Fresupporting

confidence: 90%

Visualization of the activation of the histamine H3 receptor (H3R) using novel fluorescence resonance energy transfer biosensors and their potential application to the study of H3R pharmacology

et al. 2018

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Activation of the histamine-3 receptor (H3R) is involved in memory processes and cognitive action, while blocking H3R activation can slow the progression of neurological disorders, such as Alzheimer's disease, schizophrenia and narcolepsy. To date, however, no direct way to examine the activation of H3R has been utilized. Here, we describe a novel biosensor that can visualize the activation of H3R through an intramolecular fluorescence resonance energy transfer (FRET) signal. To achieve this, we constructed an intramolecular H3R FRET sensor with cyan fluorescent protein (CFP) attached at the C terminus and yellow fluorescent protein (YFP) inserted into the third intracellular loop. The sensor was found to internalize normally on agonist treatment. We measured FRET signals between the donor CFP and the acceptor YFP in living cells in real time, the results of which indicated that H3R agonist treatment (imetit or histamine) increases the FRET signal in a time- and concentration-dependent manner with Kon and Koff values consistent with published data and which maybe correlated with decreasing cAMP levels and the promotion of ERK1/2 phosphorylation. The FRET signal was inhibited by H3R antagonists, and the introduction of mutations at F419A, F423A, L426A and L427A, once again, the promotion of ERK1/2 phosphorylation, was diminished. Thus, we have built a H3R biosensor which can visualize the activation of receptor through real-time structure changes and which can obtain pharmacological kinetic data at the same time. The FRET signals may allow the sensor to become a useful tool for screening compounds and optimizing useful ligands.

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Section: Agonist-induced Activation Of Intramolecular H3 Receptor Fresupporting

confidence: 90%

Visualization of the activation of the histamine H3 receptor (H3R) using novel fluorescence resonance energy transfer biosensors and their potential application to the study of H3R pharmacology

et al. 2018

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“…10,11 HRH3 has also several unusual properties, demonstrating high constitutive activity [12][13][14] and a large number of functional isoforms resulting from alternative splicing. 15,16 HRH3 has been implicated to inhibit the release of monoamines and other neurotransmitters, presumably as a presynaptic receptor, [17][18][19] although direct evidence of the transmitter phenotype of neurons expressing HRH3 is still lacking. 1,20 HRH3 is also capable of forming dimers with dopamine receptors DRD1 and DRD2 and alter the signalling at these receptors, which further underlies the significance of HRH3 in the regulation of dopamine signalling.…”

Section: Introductionmentioning

confidence: 99%

Knockout of histamine receptor H3 alters adaptation to sudden darkness and monoamine levels in the zebrafish

et al. 2017

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“…In the human, H 3 R isoforms demonstrate differences in pharmacologic activity [33], [34], [35]. Many of these isoforms differ from the full length transcript by a variable-length deletion in the third IC loop.…”

Section: Resultsmentioning

confidence: 99%

Histamine H3 Receptor Integrates Peripheral Inflammatory Signals in the Neurogenic Control of Immune Responses and Autoimmune Disease Susceptibility

et al. 2013

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Histamine H3 receptor (Hrh3/H3R) is primarily expressed by neurons in the central nervous system (CNS) where it functions as a presynaptic inhibitory autoreceptor and heteroreceptor. Previously, we identified an H3R-mediated central component in susceptibility to experimental allergic encephalomyelitis (EAE), the principal autoimmune model of multiple sclerosis (MS), related to neurogenic control of blood brain barrier permeability and peripheral T cell effector responses. Furthermore, we identified Hrh3 as a positional candidate for the EAE susceptibility locus Eae8. Here, we characterize Hrh3 polymorphisms between EAE-susceptible and resistant SJL and B10.S mice, respectively, and show that Hrh3 isoform expression in the CNS is differentially regulated by acute peripheral inflammatory stimuli in an allele-specific fashion. Next, we show that Hrh3 is not expressed in any subpopulations of the immune compartment, and that secondary lymphoid tissue is anatomically poised to be regulated by central H3R signaling. Accordingly, using transcriptome analysis, we show that, inflammatory stimuli elicit unique transcriptional profiles in the lymph nodes of H3RKO mice compared to WT mice, which is indicative of negative regulation of peripheral immune responses by central H3R signaling. These results further support a functional link between the neurogenic control of T cell responses and susceptibility to CNS autoimmune disease coincident with acute and/or chronic peripheral inflammation. Pharmacological targeting of H3R may therefore be useful in preventing the development and formation of new lesions in MS, thereby limiting disease progression.

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Genomic organization and characterization of splice variants of the human histamine H3 receptor

Cited by 92 publications

References 19 publications

Visualization of the activation of the histamine H3 receptor (H3R) using novel fluorescence resonance energy transfer biosensors and their potential application to the study of H3R pharmacology

Visualization of the activation of the histamine H3 receptor (H3R) using novel fluorescence resonance energy transfer biosensors and their potential application to the study of H3R pharmacology

Knockout of histamine receptor H3 alters adaptation to sudden darkness and monoamine levels in the zebrafish

Histamine H3 Receptor Integrates Peripheral Inflammatory Signals in the Neurogenic Control of Immune Responses and Autoimmune Disease Susceptibility

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