Premium
Permissive role of adenosine A 2A receptors on metabotropic glutamate receptor 5 (mGluR5)‐mediated effects in the striatum
Author(s) -
Domenici M. R.,
Pepponi R.,
Martire A.,
Tebano M. T.,
Potenza R. L.,
Popoli P.
Publication year - 2004
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.1471-4159.2004.02607.x
Subject(s) - metabotropic receptor , metabotropic glutamate receptor 5 , agonist , pharmacology , metabotropic glutamate receptor , striatum , glutamate receptor , ionotropic effect , chemistry , adenosine a2a receptor , antagonist , neuroscience , medicine , biology , receptor , adenosine receptor , biochemistry , dopamine
The metabotropic glutamate receptors 5 (mGlu5Rs) and the adenosine A 2A receptors (A 2A Rs) have been reported to functionally interact in the striatum. The aim of the present work was to verify the hypothesis that the state of activation of A 2A Rs could influence mGlu5R‐mediated effects in the striatum. In electrophysiological experiments (extracellular recording in rat corticostriatal slices), the ability of the selective mGlu5R agonist CHPG to potentiate the reduction of the field potential amplitude induced by NMDA was prevented not only by the selective mGlu5R antagonist MPEP, but also by the selective A 2A R antagonist ZM 241385. Analogously, the application of CHPG potentiated NMDA‐induced toxicity (measured by LDH release) in cultured striatal neurons, an effect that was abolished by both MPEP and ZM 241385. Finally, the A 2A R agonist CGS 21680 potentiated CHGP effects, an action that was reproduced and abolished, respectively, by forskolin (an activator of the cAMP/protein kinase A, PKA, pathway) and KT 5720 (a PKA inhibitor). The results indicate that A 2A Rs exert a permissive role on mGlu5R‐induced effects in the striatum. Such an interaction may represent an additional target for the development of therapeutic strategies towards striatal disorders.