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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Brugarolas, Marc Mallol, Josefa Navarro, Gemma Bonaventura, Jordi Lluís, Carme Rea, William Casadó-anguera, Verònica Schiffmann, Serge N. Canela, Enric I. Moreno, Estefanía Azdad, Karima Cortés, Antoni Casadó, Vicent Volkow, Nora D. Ferré, Sergi |
| Description | Author Affiliation: Bonaventura J ( Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, and Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas and Institute of Biomedicine of the University of Barcelona, 08028 Barcelona, Spain); Navarro G ( Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, and Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas and Institute of Biomedicine of the University of Barcelona, 08028 Barcelona, Spain); Casadó-Anguera V ( Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, and Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas and Institute of Biomedicine of the University of Barcelona, 08028 Barcelona, Spain); Azdad K ( Laboratory of Neurophysiology, Universite Libre de Bruxelles-Neuroscience Institute, 1070 Brussels, Belgium); Rea W ( Integrative Neurobiology Section, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD 21224); Moreno E ( Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, and Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas and Institute of Biomedicine of the University of Barcelona, 08028 Barcelona, Spain); Brugarolas M ( Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, and Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas and Institute of Biomedicine of the University of Barcelona, 08028 Barcelona, Spain); Mallol J ( Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, and Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas and Institute of Biomedicine of the University of Barcelona, 08028 Barcelona, Spain); Canela EI ( Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, and Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas and Institute of Biomedicine of the University of Barcelona, 08028 Barcelona, Spain); Lluís C ( Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, and Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas and Institute of Biomedicine of the University of Barcelona, 08028 Barcelona, Spain); Cortés A ( Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, and Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas and Institute of Biomedicine of the University of Barcelona, 08028 Barcelona, Spain); Volkow ND ( National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892.); Schiffmann SN ( Laboratory of Neurophysiology, Universite Libre de Bruxelles-Neuroscience Institute, 1070 Brussels, Belgium); Ferré S ( Integrative Neurobiology Section, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD 21224); Casadó V ( Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, and Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas and Institute of Biomedicine of the University of Barcelona, 08028 Barcelona, Spain); |
| Abstract | Adenosine A2A receptor (A2AR)-dopamine D2 receptor (D2R) heteromers are key modulators of striatal neuronal function. It has been suggested that the psychostimulant effects of caffeine depend on its ability to block an allosteric modulation within the A2AR-D2R heteromer, by which adenosine decreases the affinity and intrinsic efficacy of dopamine at the D2R. We describe novel unsuspected allosteric mechanisms within the heteromer by which not only A2AR agonists, but also A2AR antagonists, decrease the affinity and intrinsic efficacy of D2R agonists and the affinity of D2R antagonists. Strikingly, these allosteric modulations disappear on agonist and antagonist coadministration. This can be explained by a model that considers A2AR-D2R heteromers as heterotetramers, constituted by A2AR and D2R homodimers, as demonstrated by experiments with bioluminescence resonance energy transfer and bimolecular fluorescence and bioluminescence complementation. As predicted by the model, high concentrations of A2AR antagonists behaved as A2AR agonists and decreased D2R function in the brain. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 27 |
| Volume Number | 112 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2015-07-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Corpus Striatum Metabolism Protein Multimerization Receptor, Adenosine A2A Receptors, Dopamine D2 Adenosine A2 Receptor Agonists Pharmacology Adenosine A2 Receptor Antagonists Animals Binding, Competitive Drug Effects Bioluminescence Resonance Energy Transfer Techniques CHO Cells Cricetinae Cricetulus Dopamine Agonists Dopamine D2 Receptor Antagonists Dose-Response Relationship, Drug HEK293 Cells Kinetics Microscopy, Confocal Protein Binding Rats, Sprague-Dawley Chemistry Time Factors Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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