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ABSTRACT Adenosine is released from metabolically active cells by facilitated diffusion, and is generated extracellularly by degradation of released ATP. It is a potent biological mediator
that modulates the activity of numerous cell types, including various neuronal populations, platelets, neutrophils and mast cells, and smooth muscle cells in bronchi and vasculature. Most of
these effects help to protect cells and tissues during stress conditions such as ischaemia. Adenosine mediates its effects through four receptor subtypes: the A1, A2a, A2b and A3
receptors1. The A2a receptor (A2aR)2,3 is abundant in basal ganglia, vasculature and platelets, and stimulates adenylyl cyclase. It is a major target of caffeine, the most widely used
psychoactive drug4. Here we investigate the role of the A2a receptor by disrupting the gene in mice. We found that A2aR-knockout (A2aR−/−) mice were viable and bred normally. Their
exploratory activity was reduced, whereas caffeine, which normally stimulates exploratory behaviour, became a depressant of exploratory activity. Knockout animals scored higher in anxiety
tests, and male mice were much more aggressive towards intruders. The response of A2aR−/−mice to acute pain stimuli was slower. Blood pressure and heart rate were increased, as well as
platelet aggregation. The specific A2a agonist CGS 21680 lost its biological activity in all systems tested. Access through your institution Buy or subscribe This is a preview of
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IN TRAIT ANXIETY: MODULATORY EFFECTS OF MINOCYCLINE Article Open access 30 July 2020 UNIQUE BRAIN ENDOTHELIAL PROFILES ACTIVATED BY SOCIAL STRESS PROMOTE CELL ADHESION, PROSTAGLANDIN E2
SIGNALING, HYPOTHALAMIC–PITUITARY–ADRENAL AXIS MODULATION, AND ANXIETY Article 14 September 2022 HEMOKININ-1 IS A MEDIATOR OF CHRONIC RESTRAINT STRESS-INDUCED PAIN Article Open access 16
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CAS Google Scholar Download references ACKNOWLEDGEMENTS The R1 ES and STP cell lines were provided by A. Nagy and B. Colledge, respectively. We thank J.-F. Aubert for his help with the
determination ofthe haemodynamic parameters; O. Le Moine, H. Louis, D. Penninck and C. Kucharzewski for discussion; and E. Bressy, M. J. Simons, E. Quertainmont and M. Verslype for technical
assistance. This work was supported by the Belgian programme on Interuniversity Poles of Attraction initiated by the Belgian State, Prime Minister's Office, Federal Service for
Science, Technology and Culture. It was also supported by the Fonds de la Recherche Scientifique Médicale of Belgium, the BIOMED2 programme, and the Foundation Médicale Reine Elisabeth.
Scientific responsiblity belongs to the authors. C.L. and S.N.S. are Chercheurs Qualifiés of the Fonds National de la Recherche Scientifique. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS *
IRIBHN, Université Libre de Bruxelles, Campus Erasme, 808 route de Lennik, B-1070, Bruxelles, Belgium Catherine Ledent, Gilbert Vassart & Marc Parmentier * Laboratoire de Recherche sur
les Neuropeptides, Université Libre de Bruxelles, Campus Erasme, 808 route de Lennik, B-1070, Bruxelles, Belgium Serge N. Schiffmann & Jean-Jacques Vanderhaeghen * Service de Génétique
Médicale, Université Libre de Bruxelles, Campus Erasme, 808 route de Lennik, B-1070, Bruxelles, Belgium Gilbert Vassart * IFRMP, Unité de Neuropsychopharmacologie Expérimentale, CNRS UPRESA
6036, Faculté de Médecine et de Pharmacie, Avenue de l'Université, 76803 Saint Etienne du Rouvray, France Jean-Marie Vaugeois, Malika El Yacoubi & Jean Costentin * Division of
Hypertension, Lausanne University Medical School, CH-1011 Lausanne, Switzerland Thierry Pedrazzini * Department of Biochemistry, CRC Growth Factors, University of Oxford, South Parks Road,
OX1 3QU, Oxford, UK John K. Heath Authors * Catherine Ledent View author publications You can also search for this author inPubMed Google Scholar * Jean-Marie Vaugeois View author
publications You can also search for this author inPubMed Google Scholar * Serge N. Schiffmann View author publications You can also search for this author inPubMed Google Scholar * Thierry
Pedrazzini View author publications You can also search for this author inPubMed Google Scholar * Malika El Yacoubi View author publications You can also search for this author inPubMed
Google Scholar * Jean-Jacques Vanderhaeghen View author publications You can also search for this author inPubMed Google Scholar * Jean Costentin View author publications You can also search
for this author inPubMed Google Scholar * John K. Heath View author publications You can also search for this author inPubMed Google Scholar * Gilbert Vassart View author publications You
can also search for this author inPubMed Google Scholar * Marc Parmentier View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR
Correspondence to Marc Parmentier. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Ledent, C., Vaugeois, JM., Schiffmann, S. _et al._ Aggressiveness,
hypoalgesia and high blood pressure in mice lacking the adenosine A2a receptor. _Nature_ 388, 674–678 (1997). https://doi.org/10.1038/41771 Download citation * Received: 21 April 1997 *
Accepted: 05 June 1997 * Issue Date: 14 August 1997 * DOI: https://doi.org/10.1038/41771 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get
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