Adenosine A2A-D2 Receptor-Receptor Interactions in Putative Heteromers in the Regulation of the Striato-Pallidal GABA Pathway: Possible Relevance for Parkinson`s Disease and its Treatment

Author(s): Sarah Beggiato , Tiziana Antonelli , Maria C. Tomasini , Andrea C. Borelli , Luigi F. Agnati , Sergio Tanganelli , Kjell Fuxe , Luca Ferraro .

Journal Name: Current Protein & Peptide Science

Volume 15 , Issue 7 , 2014

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Abstract:

Striatal dopamine adenosine A2A and D2 receptors interact to modulate some aspects of motor and motivational function. The demonstration of A2A/D2 receptor heteromerization in living cells constituted a progress for understanding the neurobiology of dopamine D2 and adenosine A2A receptors. In fact, the existence of putative striatalA2A/D2 receptor heteromers has been suggested to be important for striatal function under both normal and pathological conditions, such as Parkinson’s disease. Consequently, the antagonistic A2A-D2 receptor interactions in a putative striatal receptor heteromer on striato-pallidal GABA neuron led to the introduction of A2A receptor antagonists as possible anti- Parkinsonian drugs. The present mini-review briefly summarizes the main findings supporting the presence of antagonistic A2A-D2 receptor interactions in putative receptor heteromers in the basal ganglia. Special emphasis is given to in vivo microdialysis findings demonstrating the functional role putative A2A/D2 heteromers on striato-pallidal GABA neurons play in the modulation of this pathway, in which A2A receptors inhibit D2 receptor signaling. The possible relevance of compounds targeting the putative striatal A2A/D2 heteromer in the Parkinson’s disease pharmacological treatment is also discussed.

Keywords: A2A receptor antagonists, D2 receptor agonists, GABA and glutamate levels, heteromeric receptor complexes, microdialysis, Parkinson's disease, receptor-receptor interaction.

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Article Details

VOLUME: 15
ISSUE: 7
Year: 2014
Page: [673 - 680]
Pages: 8
DOI: 10.2174/1389203715666140901103205
Price: $58

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