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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Adenosine A2A receptor-antagonist/dopamine D2 receptor-agonist bivalent ligands as pharmacological tools to detect A 2A-D2 receptor heteromers
Journal of Medicinal Chemistry, Volume 52, No. 18, Year 2009
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Description
Adenosine A2A (A2AR) and dopamine D2 (D2R) receptors mediate the antagonism between adenosinergic and dopaminergic transmission in striatopallidal GABAergic neurons and are pharmacological targets for the treatment of Parkinson's disease.Here, a family of heterobivalent ligands containing a D2R agonist and an A 2AR antagonist linked through a spacer of variable size was designed and synthesized to study A2AR-D2R heteromers. Bivalent ligands with shorter linkers bound to D2R or A2AR with higher affinity than the corresponding monovalent controls in membranes from brain striatum and from cells coexpressing both receptors. In contrast, no differences in affinity of bivalent versus monovalent ligands were detected in experiments using membranes from cells expressing only one receptor. These findings indicate the existence of A2AR-D2R heteromers and of a simultaneous interaction of heterobivalent ligands with both receptors. The cooperative effect derived from the simultaneous interaction suggests the occurrence of A2AR-D2R heteromers in cotransfected cells and in brain striatum. The dopamine/adenosine bivalent action could constitute a novel concept in Parkinson's disease pharmacotherapy. © 2009 American Chemical Society.
Authors & Co-Authors
Molero Milan, Anabel
Spain, Barcelona
Universitat de Barcelona
Alberício, Fernando
Spain, Barcelona
Irb Barcelona - Institute for Research in Biomedicine
Spain, Barcelona
Universitat de Barcelona
Spain, Madrid
Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina
Royo, Míriam
Spain, Barcelona
Universitat de Barcelona
Spain, Madrid
Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina
Statistics
Citations: 127
Authors: 3
Affiliations: 5
Identifiers
Doi:
10.1021/jm900298c
ISSN:
00222623