scholarly journals Affinity Mass Spectrometry-Based Fragment Screening Identified a New Negative Allosteric Modulator of the Adenosine A2A Receptor Targeting the Sodium Ion Pocket

2021 ◽  
Author(s):  
Yan Lu ◽  
Hongyue Liu ◽  
Dehua Yang ◽  
Li Zhong ◽  
Ye Xin ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Adenosine A2a Receptor ◽  
Sodium Ion ◽  
Allosteric Modulator ◽  
Receptor Targeting ◽  
Fragment Screening ◽  
A2a Receptor ◽  
Negative Allosteric Modulator ◽  
Adenosine A2a

5′-Substituted Amiloride Derivatives as Allosteric Modulators Binding in the Sodium Ion Pocket of the Adenosine A2A Receptor

2016 ◽  
Vol 59 (10) ◽  
pp. 4769-4777 ◽  
Author(s):  
Arnault Massink ◽  
Julien Louvel ◽  
Ilze Adlere ◽  
Corine van Veen ◽  
Berend J. H. Huisman ◽  
...  
Keyword(s):  
Adenosine A2a Receptor ◽  
Sodium Ion ◽  
Allosteric Modulators ◽  
A2a Receptor ◽  
Amiloride Derivatives ◽  
Adenosine A2a

scholarly journals Revisiting the Allosteric Regulation of Sodium Cation on the Binding of Adenosine at the Human A2A Adenosine Receptor: Insights from Supervised Molecular Dynamics (SuMD) Simulations

Molecules ◽  
2019 ◽  
Vol 24 (15) ◽  
pp. 2752 ◽  
Author(s):  
Maicol Bissaro ◽  
Giovanni Bolcato ◽  
Giuseppe Deganutti ◽  
Mattia Sturlese ◽  
Stefano Moro
Keyword(s):  
Molecular Dynamics ◽  
Sodium Cation ◽  
Point Of View ◽  
Sodium Ion ◽  
Transmembrane Helices ◽  
A2a Adenosine Receptor ◽  
Recognition Mechanism ◽  
A2a Receptor ◽  
Negative Allosteric Modulator ◽  
Adenosine A2a

One of the most intriguing findings highlighted from G protein-coupled receptor (GPCR) crystallography is the presence, in many members of class A, of a partially hydrated sodium ion in the middle of the seven transmembrane helices (7TM) bundle. In particular, the human adenosine A2A receptor (A2A AR) is the first GPCR in which a monovalent sodium ion was crystallized in a distal site from the canonical orthosteric one, corroborating, from a structural point of view, its role as a negative allosteric modulator. However, the molecular mechanism by which the sodium ion influences the recognition of the A2A AR agonists is not yet fully understood. In this study, the supervised molecular dynamics (SuMD) technique was exploited to analyse the sodium ion recognition mechanism and how its presence influences the binding of the endogenous agonist adenosine. Due to a higher degree of flexibility of the receptor extracellular (EC) vestibule, we propose the sodium-bound A2A AR as less efficient in stabilizing the adenosine during the different steps of binding.

scholarly journals Sodium Ion Binding Pocket Mutations and Adenosine A2A Receptor Function

2014 ◽  
Vol 87 (2) ◽  
pp. 305-313 ◽  
Author(s):  
Arnault Massink ◽  
Hugo Gutiérrez-de-Terán ◽  
Eelke B. Lenselink ◽  
Natalia V. Ortiz Zacarías ◽  
Lizi Xia ◽  
...  
Keyword(s):  
Binding Pocket ◽  
Adenosine A2a Receptor ◽  
Sodium Ion ◽  
Ion Binding ◽  
Receptor Function ◽  
A2a Receptor ◽  
Adenosine A2a

Synthesis of the Adenosine A2A Receptor Fluorescent Agonist MRS5424

BIO-PROTOCOL ◽  
2014 ◽  
Vol 4 (6) ◽  
Author(s):  
Kenneth Jacobson ◽  
Francisco Ciruela
Keyword(s):  
Adenosine A2a Receptor ◽  
A2a Receptor ◽  
Adenosine A2a

Optimization of the Human Adenosine A2a Receptor Yields in Saccharomyces cerevisiae

2008 ◽  
Vol 22 (5) ◽  
pp. 1249-1255 ◽  
Author(s):  
Alison Wedekind ◽  
Michelle A. O'Malley ◽  
Ronald T. Niebauer ◽  
Anne S. Robinson
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Adenosine A2a Receptor ◽  
A2a Receptor ◽  
Adenosine A2a

scholarly journals A Cellular Assay for the Identification and Characterization of Connexin Gap Junction Modulators

2021 ◽  
Vol 22 (3) ◽  
pp. 1417
Author(s):  
Azeem Danish ◽  
Robin Gedschold ◽  
Sonja Hinz ◽  
Anke C. Schiedel ◽  
Dominik Thimm ◽  
...  
Keyword(s):  
Gap Junctions ◽  
Small Molecules ◽  
High Throughput Screening ◽  
Cell Communication ◽  
Receptor Activation ◽  
Adenosine A2a Receptor ◽  
Intracellular Camp ◽  
Donor Cells ◽  
A2a Receptor ◽  
Adenosine A2a

Connexin gap junctions (Cx GJs) enable the passage of small molecules and ions between cells and are therefore important for cell-to-cell communication. Their dysfunction is associated with diseases, and small molecules acting as modulators of GJs may therefore be useful as therapeutic drugs. To identify GJ modulators, suitable assays are needed that allow compound screening. In the present study, we established a novel assay utilizing HeLa cells recombinantly expressing Cx43. Donor cells additionally expressing the Gs protein-coupled adenosine A2A receptor, and biosensor cells expressing a cAMP-sensitive GloSensor luciferase were established. Adenosine A2A receptor activation in the donor cells using a selective agonist results in intracellular cAMP production. The negatively charged cAMP migrates via the Cx43 gap junctions to the biosensor cells and can there be measured by the cAMP-dependent luminescence signal. Cx43 GJ modulators can be expected to impact the transfer of cAMP from the donor to the biosensor cells, since cAMP transit is only possible via GJs. The new assay was validated by testing the standard GJ inhibitor carbenoxolon, which showed a concentration-dependent inhibition of the signal and an IC50 value that was consistent with previously reported values. The assay was demonstrated to be suitable for high-throughput screening.

scholarly journals Correlation between low adenosine A2A receptor expression and hypercholesterolemia: A new component of the cardiovascular risk?

2021 ◽  
Vol 1866 (2) ◽  
pp. 158850
Author(s):  
Donato Vairo ◽  
Carola Giacobbe ◽  
Claire Guiol ◽  
Marie-Charlotte Chaptal ◽  
Maria Donata Di Taranto ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Adenosine A2a Receptor ◽  
Receptor Expression ◽  
A2a Receptor ◽  
Adenosine A2a
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