A Versatile Sub-Nanomolar Fluorescent Ligand Enables NanoBRET Binding Studies and Single-Molecule Microscopy at the Histamine H3 Receptor

2021 ◽  
Author(s):  
Niklas Rosier ◽  
Lukas Grätz ◽  
Hannes Schihada ◽  
Jan Möller ◽  
Ali Işbilir ◽  
...  
Keyword(s):  
Single Molecule ◽  
Single Molecule Microscopy ◽  
Binding Studies ◽  
Histamine H3 Receptor ◽  
H3 Receptor ◽  
Fluorescent Ligand ◽  
Histamine H3

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

2001 ◽  
Vol 355 (2) ◽  
pp. 279-288 ◽  
Author(s):  
Francis COGÉ ◽  
Sophie-Pénélope GUÉNIN ◽  
Valérie AUDINOT ◽  
Anne RENOUARD-TRY ◽  
Philippe BEAUVERGER ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Cho Cells ◽  
Genomic Organization ◽  
Splice Variants ◽  
Relative Distribution ◽  
Binding Studies ◽  
Histamine H3 Receptor ◽  
H3 Receptor ◽  
Human Histamine ◽  
Histamine H3

In the present paper we report the genomic organization of the human histamine H3-receptor gene, which consists of four exons spanning 5.5kb on chromosome 20. Using PCR, six alternative splice variants of the H3 receptor were cloned from human thalamus. These variants were found to be coexpressed in human brain, but their relative distribution varied in a region-specific manner. These isoforms displayed either a deletion in the putative second transmembrane domain (TM), H3(∆TM2, 431aa) or a variable deletion in the third intracellular loop (i3), H3(∆i3, 415aa), H3(∆i3, 365aa), H3(∆i3, 329aa) and H3(∆TM5+∆i3, 326aa). In order to determine the biological role of the H3 receptor variants compared with the ‘original’ H3(445aa) receptor, three isoforms, namely H3(445aa), H3(∆TM2, 431aa) and H3(∆i3, 365aa), were expressed in CHO cells and their pharmacological properties were investigated. Binding studies showed that H3(∆TM2,431aa) transiently expressed in CHO cells was unable to bind [125I]iodoproxyfan, whereas both the H3(445aa) and H3(∆i3, 365aa) receptors displayed a high affinity for [125I]iodoproxyfan [Kd = 28±5pM (n = 4) and 8±1pM (n = 5) respectively]. In addition, H3(∆i3, 365aa) possessed the same pharmacological profile as the H3(445aa) receptor. However, in CHO cells expressing H3(∆i3, 365aa), H3 agonists did not inhibit forskolin-induced cAMP production, stimulate [35S]guanosine 5′-[γ-thio]triphosphate ([35S]GTP[S]) binding or stimulate intracellular Ca2+ mobilization. Therefore the 80-amino-acid sequence located at the C-terminal portion of i3 plays an essential role in H3 agonist-mediated signal transduction. The existence of multiple H3 isoforms with different signal transduction capabilities suggests that H3-mediated biological functions might be tightly regulated through alternative splicing mechanisms.

Diether (substituted) piperidine derivatives as novel, histamine H3 receptor ligands

2009 ◽  
Vol 58 (S1) ◽  
pp. 47-48
Author(s):  
K. J. Kuder ◽  
X. Ligneau ◽  
J.-C. Camelin ◽  
D. Łażewska ◽  
J.-C. Schwartz ◽  
...  
Keyword(s):  
Receptor Ligands ◽  
Histamine H3 Receptor ◽  
H3 Receptor ◽  
Histamine H3

scholarly journals Purification of a histamine H3 receptor negatively coupled to phosphoinositide turnover in the human gastric cell line HGT1.

1992 ◽  
Vol 267 (35) ◽  
pp. 25315-25320
Author(s):  
Y Cherifi ◽  
C Pigeon ◽  
M Le Romancer ◽  
A Bado ◽  
F Reyl-Desmars ◽  
...  
Keyword(s):  
Cell Line ◽  
Histamine H3 Receptor ◽  
Gastric Cell ◽  
Phosphoinositide Turnover ◽  
H3 Receptor ◽  
Histamine H3

Ameliorating effects of histamine H3 receptor antagonist E177 on acute pentylenetetrazole-induced memory impairments in rats

2021 ◽  
Vol 405 ◽  
pp. 113193
Author(s):  
Alaa Alachkar ◽  
Mohamed Lotfy ◽  
Ernest Adeghate ◽  
Dorota Łażewska ◽  
Katarzyna Kieć-Kononowicz ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Histamine H3 Receptor ◽  
Memory Impairments ◽  
H3 Receptor ◽  
Histamine H3

005 Samelisant (SUVN-G3031), a histamine H3 receptor inverse agonist in animal models of sleep disorders

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A2-A2
Author(s):  
Saivishal Daripelli ◽  
Parusharamulu Molgara ◽  
Nageswararao Muddana ◽  
Pradeep Jayarajan ◽  
Venkat Reddy Mekala ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Radioligand Binding ◽  
Research Work ◽  
Brain Regions ◽  
Inverse Agonist ◽  
Abuse Liability ◽  
Histamine H3 Receptor ◽  
H3 Receptor ◽  
Histamine H3

Abstract Introduction Narcolepsy is a chronic sleep disorder characterized by overwhelming daytime drowsiness, sudden attacks of sleep and sometimes accompanied by cataplexy. Although the orexin deficiency is considered to be the primary cause of this disorder, lot of attention has been diverted on targeting histaminergic neurotransmission by blockade of histamine H3 receptor (H3R). Samelisant (SUVN-G3031) is one of the potent and selective H3R inverse agonist currently being evaluated in a Phase 2 study as monotherapy for the treatment of narcolepsy with and without cataplexy (ClinicalTrials.gov Identifier: NCT04072380). In the current research work, Samelisant was evaluated for neurotransmitter changes in rats and sleep EEG in orexin knockout mice, a reliable proof-of-concept study for treatment of excessive daytime sleepiness and cataplexy in narcolepsy. Methods Binding affinity of Samelisant towards human and rat histamine H3R was evaluated in in-vitro radioligand binding assay and functionality in GTP□S assay. Effect of Samelisant was studied in (R)-α-methyl histamine induced dipsogenia. In rat brain microdialysis, Samelisant was evaluated for its effects on modulation of neurotransmitters like histamine, dopamine and norepinephrine. Male orexin knockout mice were implanted with telemetric device for simultaneous monitoring of electroencephalography (EEG) and electromyography. Effects of Samelisant (3 and 10 mg/kg, p.o.) were evaluated during active period of animals. Results Samelisant is an inverse agonist at histamine H3 receptors with hKi of 8.7 nM and showed minimal binding against over 70 target sites. Samelisant produced significant increase in histamine, dopamine and norepinephrine levels in cortex. Samelisant produced no change in the striatal and accumbal dopamine levels in rats, suggesting no propensity to induce abuse liability. Samelisant blocked R-α-methyl histamine induced water intake and produced dose dependent increase in tele-methylhistamine levels in various brain regions and in cerebrospinal fluid of male Wistar rats. Samelisant produced significant increase in wakefulness with concomitant decrease in non-rapid eye movement sleep in orexin knockout mice. Samelisant also significantly decreased number of cataplectic episodes in orexin knockout mice. Conclusion Samelisant is an inverse agonist at histamine H3 receptor and results from the preclinical studies presented here provide a strong evidence for the potential utility of Samelisant in the treatment of narcolepsy with and without cataplexy. Support (if any):

Chronic administration of the histamine H3 receptor agonist immepip decreases l-Dopa-induced dyskinesias in 6-hydroxydopamine-lesioned rats

2019 ◽  
Vol 236 (6) ◽  
pp. 1937-1948 ◽  
Author(s):  
Alberto Avila-Luna ◽  
Camilo Ríos ◽  
Arturo Gálvez-Rosas ◽  
Sergio Montes ◽  
José-Antonio Arias-Montaño ◽  
...  
Keyword(s):  
Receptor Agonist ◽  
Chronic Administration ◽  
Histamine H3 Receptor ◽  
H3 Receptor ◽  
6 Hydroxydopamine ◽  
Histamine H3

A CoMFA study of histamine H3 receptor agonists

1996 ◽  
Vol 4 ◽  
pp. S117 ◽  
Author(s):  
Jukka Gynther ◽  
Antti Poso ◽  
Jari Kova;ainen ◽  
Hans Christiaans ◽  
Leena Tuomisto
Keyword(s):  
Histamine H3 Receptor ◽  
Receptor Agonists ◽  
H3 Receptor ◽  
Comfa Study ◽  
Histamine H3

ChemInform Abstract: 4-Chlorobenzyl Sulfonamide and Sulfamide Derivatives of Histamine Homologues: The Design of Potent Histamine H3 Receptor Antagonists.

ChemInform ◽  
2010 ◽  
Vol 31 (8) ◽  
pp. no-no
Author(s):  
Matthew J. Tozer ◽  
Ildiko M. Buck ◽  
Tracey Cooke ◽  
S. Barret Kalindjian ◽  
Iain M. McDonald ◽  
...  
Keyword(s):  
Receptor Antagonists ◽  
Histamine H3 Receptor ◽  
H3 Receptor ◽  
Derivatives Of ◽  
Histamine H3
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