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.
Current Protein & Peptide Science
Title: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
Volume: 15 Issue: 7
Author(s): Sarah Beggiato, Tiziana Antonelli, Maria C. Tomasini, Andrea C. Borelli, Luigi F. Agnati, Sergio Tanganelli, Kjell Fuxe and Luca Ferraro
Affiliation:
Keywords: A2A receptor antagonists, D2 receptor agonists, GABA and glutamate levels, heteromeric receptor complexes, microdialysis, Parkinson's disease, receptor-receptor interaction.
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.
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Beggiato Sarah, Antonelli Tiziana, Tomasini C. Maria, Borelli C. Andrea, Agnati F. Luigi, Tanganelli Sergio, Fuxe Kjell and Ferraro Luca, 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, Current Protein & Peptide Science 2014; 15 (7) . https://dx.doi.org/10.2174/1389203715666140901103205
DOI https://dx.doi.org/10.2174/1389203715666140901103205 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
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