Title: Co-localization and functional interaction between adenosine A2A and metabotropic group 5 receptors in glutamatergic nerve terminals of the rat striatum
Authors: Rodrigues, Ricardo J. 
Alfaro, Tiago M. 
Rebola, Nelson 
Oliveira, Catarina R. 
Cunha, Rodrigo A. 
Issue Date: 2005
Citation: Journal of Neurochemistry. 92:3 (2005) 433-441
Abstract: The anti-Parkinsonian effect of glutamate metabotropic group 5 (mGluR5) and adenosine A2A 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 A2A antagonists are also neuroprotective in brain injury models involving glutamate excitotoxicity. Thus, we hypothesized that the anti-Parkinsonian and neuroprotective effects of A2A and mGluR5 receptors might be related to their control of striatal glutamate release that actually triggers the indirect pathway. The A2A agonist, CGS21680 (1201330 nm) facilitated glutamate release from striatal nerve terminals up to 57%, an effect prevented by the A2A antagonist, SCH58261 (50 nm). The mGluR5 agonist, CHPG (3002013600 03BCm) also facilitated glutamate release up to 29%, an effect prevented by the mGluR5 antagonist, MPEP (10 03BCm). Both mGluR5 and A2A receptors were located in the active zone and 57 ± 6% of striatal glutamatergic nerve terminals possessed both A2A and mGluR5 receptors, suggesting a presynaptic functional interaction. Indeed, submaximal concentrations of CGS21680 (1 nm) and CHPG (100 03BCm) synergistically facilitated glutamate release and the facilitation of glutamate release by 10 nm CGS21680 was prevented by 10 03BCm MPEP, whereas facilitation by 300 03BCm CHPG was prevented by 10 nm SCH58261. These results provide the first direct evidence that A2A 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.
URI: http://hdl.handle.net/10316/8420
Rights: openAccess
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais

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