Comparison of the pharmacological properties of human and rat histamine H3-receptors

Schnell, David; Straßer, Andrea; Seifert, Roland

doi:10.1016/j.bcp.2010.07.027

Cited by 27 publications

(32 citation statements)

References 44 publications

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“…In agreement with this concept, the human and rat H 3 receptors recombinantly expressed in, e.g., SK-N-MC neuroblastoma cells, are negatively coupled to cAMP accumulation (Lovenberg et al, 1999. The human H 3 receptor and rat H 3 receptor expressed in Sf9 insect cells couple equally well to G i1 , G i2 , G i3 , and G o1 as assessed by measurement of steady-state GTPase activity upon H 3 receptor/G protein coexpression (Schnell et al, 2010).…”

Section: B Signal Transduction Mechanismsmentioning

confidence: 61%

International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors

et al. 2015

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Section: B Signal Transduction Mechanismsmentioning

confidence: 61%

International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors

et al. 2015

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“…In particular, a β2-adrenergic receptor based H3R model was used to understand the species-differences in pharmacological properties of imoproxifan (inverse agonist at rat H3R, but almost full agonist at human H3R) [13]. The molecular modelling studies suggested that both amino acid differences in TM3, at position 3.37 and 3.40, are responsible for the differences in imoproxifan pharmacology.…”

Section: H3 Receptormentioning

confidence: 99%

“…The availability of these structures allowed the development of better quality homology models especially for the H3 [13] and H4 [14] receptors. Finally, the first X-ray structure of the histamine H1 receptor appeared in 2011 [15] that, together with other high resolution GPCR structures, provided a solid basis for the structure-based design of ligands acting on H1, H3 and H4 receptors.…”

Section: Introductionmentioning

confidence: 99%

Structure-based discovery and binding site analysis of histamine receptor ligands

Kingsford-Adaboh

Keserü

2016

Expert Opinion on Drug Discovery

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Introduction: Application of structure-based drug discovery in histamine receptor projects was previously hampered by the lack of experimental structures. The publication of the first X-ray structure of the histamine H1 receptor has been followed by several successful virtual screens and binding site analysis studies of H1-antihistamines. This structure together with several other recently solved aminergic G-protein coupled receptors (GPCRs) enabled the development of more realistic homology models for H2, H3 and H4 receptors. Areas covered: In this paper, we review the development of histamine receptors models and their application on drug discovery. Expert opinion: In our opinion, the application of atomistic histamine receptor models played a significant role in understanding key ligand-receptor interactions as well as in the discovery of novel chemical starting points. The recently solved H1 receptor structure is a major milestone in structure-based drug discovery, however our analysis also demonstrate that for building H3 and H4 receptor homology models other GPCRs may be more suitable as a template. For these receptors we envisage that the development of higher quality homology models will significantly contribute to the discovery and optimization of novel H3 and H4 ligands.

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“…Baculoviruses encoding mH 4 R, hH 4 R, and hH 3 R were prepared as described (Schneider et al 2009;Schnell et al 2010;Schnell et al 2011). The cDNAs of mH 4 R and hH 4 R were labeled N-terminally by a Flag-epitope and C-terminally by a hexahistidine (His 6 )-tag and cloned into pcDNA3.1.…”

Section: Methodsmentioning

confidence: 99%

Commercially available antibodies against human and murine histamine H4-receptor lack specificity

Beermann

Seifert

Neumann

2011

Naunyn-Schmiedeberg's Arch Pharmacol

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Antibodies are important tools to detect expression and localization of proteins within the living cell. However, for a series of commercially available antibodies which are supposed to recognize G-protein-coupled receptors (GPCR), lack of specificity has been described. In recent publications, antisera against the histamine H₄-receptor (H₄R), which is a member of the GPCR family, have been used to demonstrate receptor expression. However, a comprehensive characterization of these antisera has not been performed yet. Therefore, the purpose of our study was to evaluate the specificity of three commercially available H₄R antibodies. Sf9 insect cells and HEK293 cells expressing recombinant murine and human H₄R, spleen cells obtained from H₄⁻/⁻ and from wild-type mice, and human CD20⁺ and CD20⁻ peripheral blood cells were analyzed by flow cytometry and Western blot using three commercially available H₄R antibodies. Our results show that all tested H₄R antibodies bind to virtually all cells, independently of the expression of H₄R, thus in an unspecific fashion. Also in Western blot, the H₄R antibodies do not bind to the specified protein. Our data underscore the importance of stringent evaluation of antibodies using valid controls, such as cells of H₄R⁻/⁻ mice, to show true receptor expression and antigen specificity. Improved validation of commercially available antibodies prior to release to the market would avoid time-consuming and expensive validation assays by the user.

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Comparison of the pharmacological properties of human and rat histamine H3-receptors

Cited by 27 publications

References 44 publications

International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors

International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors

Structure-based discovery and binding site analysis of histamine receptor ligands

Commercially available antibodies against human and murine histamine H4-receptor lack specificity

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