Identification of the Beer Component Hordenine as Food-Derived Dopamine D2 Receptor Agonist by Virtual Screening a 3D Compound Database.

Journal article
(Original article)


Publication Details

Author(s): Sommer T, Hübner H, El Kerdawy A, Gmeiner P, Pischetsrieder M, Clark T
Journal: Scientific Reports
Publication year: 2017
Volume: 7
Pages range: 44201
ISSN: 2045-2322


Abstract


The dopamine D2 receptor (D2R) is involved in food reward and compulsive food intake. The present study developed a virtual screening (VS) method to identify food components, which may modulate D2R signalling. In contrast to their common applications in drug discovery, VS methods are rarely applied for the discovery of bioactive food compounds. Here, databases were created that exclusively contain substances occurring in food and natural sources (about 13,000 different compounds in total) as the basis for combined pharmacophore searching, hit-list clustering and molecular docking into D2R homology models. From 17 compounds finally tested in radioligand assays to determine their binding affinities, seven were classified as hits (hit rate = 41%). Functional properties of the five most active compounds were further examined in β-arrestin recruitment and cAMP inhibition experiments. D2R-promoted G-protein activation was observed for hordenine, a constituent of barley and beer, with approximately identical ligand efficacy as dopamine (76%) and a Ki value of 13 μM. Moreover, hordenine antagonised D2-mediated β-arrestin recruitment indicating functional selectivity. Application of our databases provides new perspectives for the discovery of bioactive food constituents using VS methods. Based on its presence in beer, we suggest that hordenine significantly contributes to mood-elevating effects of beer.



FAU Authors / FAU Editors

Clark, Timothy apl. Prof. Dr.
Computer-Chemie-Centrum
Gmeiner, Peter Prof. Dr.
Lehrstuhl für Pharmazeutische Chemie
Hübner, Harald Dr.
Lehrstuhl für Pharmazeutische Chemie
Pischetsrieder, Monika Prof. Dr.
Lehrstuhl für Lebensmittelchemie (Henriette-Schmidt-Burkhardt Lehrstuhl)
Sommer, Thomas
Lehrstuhl für Lebensmittelchemie (Henriette-Schmidt-Burkhardt Lehrstuhl)


Additional Organisation
Emil-Fischer-Zentrum (Emil Fischer Center)


How to cite

APA:
Sommer, T., Hübner, H., El Kerdawy, A., Gmeiner, P., Pischetsrieder, M., & Clark, T. (2017). Identification of the Beer Component Hordenine as Food-Derived Dopamine D2 Receptor Agonist by Virtual Screening a 3D Compound Database. Scientific Reports, 7, 44201. https://dx.doi.org/10.1038/srep44201

MLA:
Sommer, Thomas, et al. "Identification of the Beer Component Hordenine as Food-Derived Dopamine D2 Receptor Agonist by Virtual Screening a 3D Compound Database." Scientific Reports 7 (2017): 44201.

BibTeX: 

Last updated on 2018-19-04 at 03:51