Aggressiveness, hypoalgesia and high blood pressure in mice lacking the adenosine A2a receptor

Details

Serval ID
serval:BIB_E50662B91F88
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Aggressiveness, hypoalgesia and high blood pressure in mice lacking the adenosine A2a receptor
Journal
Nature
Author(s)
Ledent  C., Vaugeois  J. M., Schiffmann  S. N., Pedrazzini  T., El Yacoubi  M., Vanderhaeghen  J. J., Costentin  J., Heath  J. K., Vassart  G., Parmentier  M.
ISSN
0028-0836 (Print)
Publication state
Published
Issued date
08/1997
Volume
388
Number
6643
Pages
674-8
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Aug 14
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 receptors. The A2a receptor (A2aR) is abundant in basal ganglia, vasculature and platelets, and stimulates adenylyl cyclase. It is a major target of caffeine, the most widely used psychoactive drug. 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.
Keywords
Adenosine/analogs & derivatives/pharmacology/physiology Aggression/physiology Animals Blood Pressure/physiology Brain/physiology Caffeine/pharmacology Cloning, Molecular Heart Rate/physiology Humans Hypertension/etiology Male Mice Mice, Knockout Molecular Sequence Data Pain Phenethylamines/pharmacology Platelet Aggregation/physiology Receptors, Purinergic P1/antagonists & inhibitors/deficiency/genetics/*physiology Restriction Mapping Sequence Homology, Amino Acid
Pubmed
Web of science
Create date
25/01/2008 8:45
Last modification date
20/08/2019 16:08
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