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Co‐localization and functional interaction between adenosine A 2A and metabotropic group 5 receptors in glutamatergic nerve terminals of the rat striatum
Author(s) -
Rodrigues Ricardo J.,
Alfaro Tiago M.,
Rebola Nelson,
Oliveira Catarina R.,
Cunha Rodrigo A.
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.1471-4159.2004.02887.x
Subject(s) - metabotropic glutamate receptor 5 , metabotropic glutamate receptor , glutamate receptor , glutamatergic , metabotropic glutamate receptor 1 , neuroscience , metabotropic glutamate receptor 7 , metabotropic glutamate receptor 2 , metabotropic receptor , metabotropic glutamate receptor 6 , pharmacology , agonist , chemistry , biology , receptor , biochemistry
The anti‐Parkinsonian effect of glutamate metabotropic group 5 (mGluR5) and adenosine A 2A receptor antagonists is believed to result from their ability to postsynaptically control the responsiveness of the indirect pathway that is hyperfunctioning in Parkinson's disease. mGluR5 and A 2A antagonists are also neuroprotective in brain injury models involving glutamate excitotoxicity. Thus, we hypothesized that the anti‐Parkinsonian and neuroprotective effects of A 2A and mGluR5 receptors might be related to their control of striatal glutamate release that actually triggers the indirect pathway. The A 2A agonist, CGS21680 (1–30 n m ) facilitated glutamate release from striatal nerve terminals up to 57%, an effect prevented by the A 2A antagonist, SCH58261 (50 n m ). The mGluR5 agonist, CHPG (300–600 μ m ) also facilitated glutamate release up to 29%, an effect prevented by the mGluR5 antagonist, MPEP (10 μ m ). Both mGluR5 and A 2A receptors were located in the active zone and 57 ± 6% of striatal glutamatergic nerve terminals possessed both A 2A and mGluR5 receptors, suggesting a presynaptic functional interaction. Indeed, submaximal concentrations of CGS21680 (1 n m ) and CHPG (100 μ m ) synergistically facilitated glutamate release and the facilitation of glutamate release by 10 n m CGS21680 was prevented by 10 μ m MPEP, whereas facilitation by 300 μ m CHPG was prevented by 10 n m SCH58261. These results provide the first direct evidence that A 2A and mGluR5 receptors are co‐located in more than half of the striatal glutamatergic terminals where they facilitate glutamate release in a synergistic manner. This emphasizes the role of the modulation of glutamate release as a likely mechanism of action of these receptors both in striatal neuroprotection and in Parkinson's disease.