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Adenosine A 2A receptor stimulation potentiates nitric oxide release by activated microglia
Author(s) -
Saura Josep,
Angulo Ester,
Ejarque Aroa,
Casadó Vicent,
Tusell Josep M.,
Moratalla Rosario,
Chen JiangFan,
Schwarzschild Michael A.,
Lluis Carme,
Franco Rafael,
Serratosa Joan
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03395.x
Subject(s) - neuroprotection , microglia , receptor , nitric oxide synthase , adenosine , agonist , receptor antagonist , adenosine a3 receptor , adenosine receptor , neuroglia , stimulation , pharmacology , chemistry , biology , nitric oxide , endocrinology , antagonist , biochemistry , central nervous system , immunology , inflammation
The absence of adenosine A 2A receptors, or its pharmacological inhibition, has neuroprotective effects. Experimental data suggest that glial A 2A receptors participate in neurodegeneration induced by A 2A receptor stimulation. In this study we have investigated the effects of A 2A receptor stimulation on control and activated glial cells. Mouse cortical mixed glial cultures (75% astrocytes, 25% microglia) were treated with the A 2A receptor agonist CGS21680 alone or in combination with lipopolysaccharide (LPS). CGS21680 potentiated lipopolysaccharide‐induced NO release and NO synthase‐II expression in a time‐ and concentration‐dependent manner. CGS21680 potentiation of lipopolysaccharide‐induced NO release was suppressed by the A 2A receptor antagonist ZM‐241385 and did not occur on mixed glial cultures from A 2A receptor‐deficient mice. In mixed glial cultures treated with LPS + CGS21680, the NO synthase‐II inhibitor 1400W abolished NO production, and NO synthase‐II immunoreactivity was observed only in microglia. Binding experiments demonstrated the presence of A 2A receptors on microglial but not on astroglial cultures. However, the presence of astrocytes was necessary for CGS21680 potentiating effect. In light of the reported neurotoxicity of microglial NO synthase‐II and the neuroprotection of A 2A receptor inhibition, these data suggest that attenuation of microglial NO production could contribute to the neuroprotection afforded by A 2A receptor antagonists.