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GDNF control of the glutamatergic cortico‐striatal pathway requires tonic activation of adenosine A 2A receptors
Author(s) -
Gomes Catarina A. R. V.,
Simões Patrícia F.,
Canas Paula M.,
Quiroz César,
Sebastião Ana M.,
Ferré Sergi,
Cunha Rodrigo A.,
Ribeiro Joaquim A.
Publication year - 2009
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.1471-4159.2009.05876.x
Subject(s) - glial cell line derived neurotrophic factor , glutamatergic , neuroscience , glutamate receptor , adenosine a2a receptor , biology , receptor , agonist , medicine , endocrinology , chemistry , adenosine receptor , neurotrophic factors , biochemistry
Glial cell line‐derived neurotrophic factor (GDNF) affords neuroprotection in Parkinson’s disease in accordance with its ability to bolster nigrostriatal innervation. We previously found that GDNF facilitates dopamine release in a manner dependent on adenosine A 2A receptor activation. As motor dysfunction also involves modifications of striatal glutamatergic innervation, we now tested if GDNF and its receptor system, Ret ( rearranged during transfection ) and GDNF family receptor α1 controlled the cortico‐striatal glutamatergic pathway in an A 2A receptor‐dependent manner. GDNF (10 ng/mL) enhanced (by ≈13%) glutamate release from rat striatal nerve endings, an effect potentiated (up to ≈30%) by the A 2A receptor agonist CGS 21680 (10 nM) and prevented by the A 2A receptor antagonist, SCH 58261 (50 nM). Triple immunocytochemical studies revealed that Ret and GDNF family receptor α1 were located in 50% of rat striatal glutamatergic terminals (immunopositive for vesicular glutamate transporters‐1/2), where they were found to be co‐located with A 2A receptors. Activation of the glutamatergic system upon in vivo electrical stimulation of the rat cortico‐striatal input induced striatal Ret phosphorylation that was prevented by pre‐treatment with the A 2A receptor antagonist, MSX‐3 (3 mg/kg). The results provide the first functional and morphological evidence that GDNF controls cortico‐striatal glutamatergic pathways in a manner largely dependent on the co‐activation of adenosine A 2A receptors.