Adenosine A2A receptors modulate glutamate uptake in cultured astrocytes and gliosomes
Glia. 2012-02-01; 60(5): 702-716
DOI: 10.1002/glia.22290
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Matos M(1), Augusto E, Santos-Rodrigues AD, Schwarzschild MA, Chen JF, Cunha RA,
Agostinho P.
Author information:
(1)Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra,
Portugal.
Glutamate is the primary excitatory neurotransmitter in the central nervous
system, where its toxic build-up leads to synaptic dysfunction and excitotoxic
cell death that underlies many neurodegenerative diseases. Therefore, efforts
have been made to understand the regulation of glutamate transporters, which are
responsible for the clearance of extracellular glutamate. We now report that
adenosine A(2A) receptors (A(2A) R) control the uptake of D-aspartate in primary
cultured astrocytes as well as in an ex vivo preparation enriched in glial
plasmalemmal vesicles (gliosomes) from adult rats, whereas A(1) R and A(3) R
were devoid of effects. Thus, the acute exposure to the A(2A) R agonist, CGS
21680, inhibited glutamate uptake, an effect prevented by the A(2A) R
antagonist, SCH 58261, and abbrogated in cultured astrocytes from A(2A) R
knockout mice. Furthermore, the prolonged activation of A(2A) R lead to a
cAMP/protein kinase A-dependent reduction of GLT-I and GLAST mRNA and protein
levels, which leads to a sustained decrease of glutamate uptake. This dual
mechanism of inhibition of glutamate transporters by astrocytic A(2A) R provides
a novel candidate mechanism to understand the ability of A(2) (A) R to control
synaptic plasticity and neurodegeneration, two conditions tightly associated
with the control of extracellular glutamate levels by glutamate transporters.
Copyright © 2012 Wiley Periodicals, Inc.